Hematology

Dr.
Azam’s
Notes in Anesthesiology
Postgraduates appearing
Updated up to December 2013, 3rd Edition for MD, DNB & DA Exams
Hematology
Edited by:
Dr. Azam
Consultant Anesthesiologist
& Critical Care Specialist
www.drazam.com
2
Dr Azam’s Notes in Anesthesiology 2013
Dedication
To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for

being my major pillar of support and making this vision a reality. Thank you for your
continual sacrifices with boundless love and limitless gratitude, for the sake of your
children. I owe you a debt I can never repay.
I also would like to thank my mom (Naaz Shafi), my wife (Roohi Azam), my two lovely
kids (Falaq Zohaa & Mohammed Izaan), for their support, ideas, patience, and
encouragement during the many hours of writing this book.
Finally, I would like to thank my teachers (Dr.Manjunath Jajoor & team) & Dr T. A. Patil . The
dream begins with a teacher who believes in you, who tugs and pushes and leads you to the next
plateau, sometimes poking you with a sharp stick called "truth."

A NOTE TO THE READER
Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience
broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the
most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the
method and duration of administration, and contraindications.
However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party
who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect
accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information
contained in this work. Readers are encouraged to confirm the information contained herein with other sources. It is the responsibility of the
licensed prescriber, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual
patient. Neither the publisher nor the editor assumes any liability for any injury and/or damage to persons or property arising from this
publication.
Dr. Azam

Contents Dr Azam’s Notes in Anesthesiology 2013
1. Blood & Blood Products - 6 25. Coagulation & Anesthesia - 79

2. Development of Red Blood Cells - 12 26. Hemophilia - 90
3. Blood Group system - 13 27. Coagulation Factors - 96
4. Blood storage System - 14 28. Artificial BloodBlood Substitutes - 97
5. Recommendation of Blood transfusion - 16 29.What is recombinant factor VIIa? Describe the clinical usage of it - 99
6. Compatibility Testing - 17
7. Blood Component therapy & Blood substitutes - 18
8. Define Massive blood transfusion. Discuss the complications
associated with massive blood transfusion - 24 & 71
9. Describe Anesthetics concerns for regional anesthesia in a
patient on anticoagulants - 28
10.What is Disseminated intravascular coagulation? Enumerate its
causes and management - 30
11.Enumerate the indications of packed red cells, fresh frozen
plasma(FFP), platelets & cryoprecipitates - 33
12.Write the blood conservative strategies in a 20 year old female
scheduled for excision of angiofibroma of nose - 35
13.Autologus Blood transfusion - 37 & 63
14.Replacement therapy for coagulation factor deficiency - 41
15.Partial thromboplastin time - PTT - 42
16. Activated Clotting Time - ACT - 43
17.Prothrombin Time - PT - 44
18. Describe the coagulation factors. How do you investigate a
case of intra operative coagulopathy - 45
19. Categorization of coagulation disorders - 47
20.Describe various test used for monitoring peri-operative
coagulation - 48
21. Thromboelastography - 51
22. Assessment of blood Loss during Surgery - 53
23. Sickle Cell Anemia & Anesthesia - 55
24. Anemia & Anesthesia - 59

1. Blood & Blood Products. Dr Azam’s Notes in Anesthesiology 2013
History: • Only in pathological situations significant hematopoietic activity occur in

• 1616 – William Harvey – circulations of blood liver, spleen and other sites during adult life and is referred to as
• 1818 – James Blundell – man to man transfusion extramedullary hematopoesis.
• 1874 – William Hagumore– suggested autologous blood Development of blood cells:
transfusion • Blood cells develop from a small population of TOTIPOTENT
• 1899 – Shaltock – noticed agglutination hematopoietic STEM CELLS which maintain their numbers by self
• 1900 – LANSTEINER – described ABO grouping replication and also gives rise to precursors of one or other of the
• 1902 – Decastello and Sturli – described AB blood group various blood cells series and cells of the immune system.
• 1916 – Rous and Turne – preservation of blood ! 3*)%"#(&)*+#((
!"#$%"&'"(&)*+#(
•! Oswald Robertson first blood bank 45.2160'$2)#&((
!"'+#,-)'"($#..&(
• 1936 – Levine and stetson – Rh.system '/()0#(-11%,#(
Blood: 7',589(,',54((
&2&)#1( .2160'$2)#&((
• Blood consists of a fluid medium, plasma, in which are
8:(;2160'$2)#&9(
suspended a number of circulating cells each with its own
highly specialized functions. 6.*&1*($#..&((
Site of blood formation:
• Production of blood cells commences in the yolk sac of the <=;>(?=!;@AB4@7C(
4D4@!D4=74(<4=3(
embryo, but then shifts to the liver and to a lesser extent the
A=;;<(
spleen, so that these organs become the dominant site of
production between the 2nd and 8th month of gestation. ="2)0"'-E(&#"-#&(F#"2)0"'$2)#&((
• The liver and spleen are then supersede by the bone marrow
which serves as the only important site of blood cell 3#+*G*"2'$2)#(F(6.*)#.#)&(((
production after birth.
3','$2)#&(F(1*$"'60*+#&(&#"-#&(F(
• Hematopoietic tissue fills all the cavities within the bones of 1','$2)#&(*,E(1*$"'60*+#&((((
the newborn, but with increasing age becomes localized in
7#%)"'60-.&(&#"-#&(F(&#+1#,)#E(((
the cavities of upper shafts of the femur, humerus, the pelvis, (((((((((((((((((((((((((((((((7#%)"'60-.&((
C"*,%.'$2)#&(
spine, skull and bones of the thorax- this is referred to as red
marrow because of its macroscopic appearance and its total ='&-,'60-.(&#"-#&(F(&#+1#,)#E((
volume is 1-2 liters. (((((((((((((((((((((((((((((((='&-,'60-.&(((
• The remaining bone marrow in the more peripheral regions 8*&'60-.(&#"-#&(F(&#+1#,)#E((((
of the skeleton contains predominantly fat, and is termed as (((((((((((((((((((((((((((((8*&'60-.&((((
YELLOW MARROW. It also occupies a volume of 1-2 liters
H?'1*,'I&G2(&)*-,&((
and serves as a space into which hematopoietic tissue can
expand in response to an increased demand for blood cell
production.

Blood & Blood Products.Continuation: Dr Azam’s Notes in Anesthesiology 2013
White Cells: Blood Volume:

• Normal white cell count: 4-11 x 109 / lit. • For normal subjects can be estimated in relation to height and
• White cells count in infancy and childhood tend to be greater weight.
than in adults, with values as high as 25 x 109 / lit at birth. After RBC volume:
1st week of life the count drops to 14 x 109 / lit. • Men: 26-33 ml/kg
• The leukocyte count undergoes minor degree of diurnal variation • Women: 22-29 ml/kg
with slight increases in the afternoon. • Plasma volume: 35-45 ml/kg
• Values of upto 15 x 109 / lit are common during pregnancy, Total blood volume:!
following parturition the count may rise to 20 x 109 / lit returning • 70ml/kg – adults
to normal values within a week. • 80ml/kg – children
Normal values for the cellular elements in human blood: • 90ml/kg – neonates
Cell Normal range Percentage • Total blood volume = plasma vol. x 100.
Total WBC 4000-11,000 ! ! ! 100 - Hematocrit
Granulocytes Distribution of blood:
Neutrophils 3000-6000 50-70% • 60-70% venous
Eosinophils 150-300 1-4% • 15% arteries
Basophils 0-100 0.4% • 10% in the heart
• 5% capillary
Lymphocytes 1500-4000 20-40%
Blood group and blood transfusion:
Monocytes 300-600 2-8% Introduction:
Erythrocytes • The anesthesiologist has to frequently use blood or blood products in
Females 4.8 x 106 treating the shocked or bleeding patient. The importance of
Males 5.4 x 106 recognizing adverse reactions associated with transfusion therapy is
Platelets 200,000-500,000 emphasized by the estimate that over half of all transfusions of blood
products are given during anesthesia. Hence knowledge of blood
groups and transfusion reactions are very important for the
anesthesiologist.
Blood groups:
• Human RBC contains on their surface a series of glycoproteins and
glycolipids which constitute the blood group antigens also called
agglutinogen. They appear early in fetal life and remain unchanged
until death. On the basis of these antigens, at least 15 well defined
blood group, systems have been described. They are the ABO, MN,
P, Rh, Lutheran, kell, Kidd, Lewis, Duffy, Diego, YE, Xg, Li, Dombrock
and cotton systems; of these only ABO and Rh systems one of major
clinical importance.
7

Blood group systems: Storage of Blood:

1) ABO system: • Several different preservative solutions can be added to either whole
• A and B antigens are inherited as Mendelian dominants, and blood or packed RBCs to allow storage of these products.
individuals are divided into 4 major blood types on this basis. • In general preservative solutions contain additives that
• Type A individuals have A ag on the RBCs a) Prevent coagulation
• Type B individuals have B ag b) Support glycolysis
• Type AB individuals have both antigens c) Maintain ATP generation
• Type O individuals have neither • The preservative determines the blood products storage on shelf life.
Several subgroups of A exist; the most important being A1 and A2. The duration of storage is determined by the requirement that at
• The difference between A1 and A2 appears to be quantitative. least 70% of the transfused red blood cells remain in circulation for
Each A1 cell has about 1,000,000 copies of the A ag on its 24 hrs after infusion.
surface and each A2 cell has about 250,000. • A unit of whole blood generally contains 450ml (± 10%) of blood and
• The A and B antigens are found in many tissues in addition to about 60ml of preservative.
blood these include salivary glands, saliva, pancreas, kidney, The various preservatives are:
liver, lungs, testes, semen and amniotic fluid. ACD (acid citrate dextrose)
• Antibodies against red cell agglutinogen are called agglutinins. • Trisodium citrate = 2.2gm /dl
• The serum of an individual contains antibodies against the Ags • Citric acid = 0.8gm/dl
lacking on the persons red cells. Thus type A individuals develop • Dextrose = 2.5gm /dl
anti B antibodies; type B individuals develop anti A abs, type O • Water upto = 100ml
individuals develop both, type AB individuals develop neither. • pH = 5.0-5.1
2) The Rh group: • 67.5ml ACD is mixed with 420-450ml of blood duration of storage =
• The Rhesus (Rh) blood group system was first demonstrated in 21 days
humans, by the use of an antiserum prepared by immunizing Preservatives:
rabbits with red cells from a rhesus monkey. It was found that • Acid citrate dextrose (ACD) -21 days
some human red cells were agglutinated by the serum “Rh +ve • Citrate phosphate dextrose (CPD) -28 days
cells” – while others were not – “Rh –ve cells”. This system is • CPD + adenine – 35 days
composed primarily of C, D and E antigens of which D is the
most important antigenic component and the term “Rh positive”
means that the individual has the D antigen and “rh –ve” means
that the individual has no D antigen.
• Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
system anti-D abs do not develop without exposure of a D –ve
individual to D +ve red cells by transfusion or entrance of fetal
blood into the maternal circulation.

CPD (citrate phosphate dextrose) 6) Frozen storage:

• Trisodium citrate ! ! - 2.6gm /dl • RBCs previously frozen to -790C in glycerol can be thawed without
• Citric acid ! ! ! - 0.327gm/dl damage; but it must be free from glycerol before being transfused.
• Sodium dihydrogen phosphate ! - 0.2gm /dl Storage time-- several years.
• Dextrose ! ! ! ! - 2.55gm /dl The advantages of frozen and thawed RBCs are the following:
• Water ! ! ! - 100 ml 1. Blood of rare types can be stored for long periods, increasing
• pH ! ! ! ! ! - 5.5 viability and eliminating outdating.
• 63ml of CPD with 450ml of whole blood storage duration – 28 2. Frozen, reconstituted blood is believed to be safer in patients who
days are especially susceptible to allergic reaction because the freezing
1. Citrate prevents clotting by binding calcium. and washing process reduces sites with histocompatible antigens.
2. Dextrose allows continuation of glycolysis of RBC and thus 3. Frozen blood, low in fibrin and leukocyte aggregates, would be
maintains sufficient concentrations of high energy ATP to safer in patients requiring massive blood transfusion.
ensure continued red blood cell metabolism and subsequence 4. Frozen washed blood may reduce risk of transfusion hepatitis.
viability during storage. 5. Frozen RBCs may be desirable in clinical conditions requiring
3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts prompt tissue oxygenation because normal levels of 2, 3-DPG are
the large fall in hydrogen ions that occur when the blood is retained in frozen erythrocytes.
cooled. Heparin:
Other preservatives • Whole blood stored in heparin is used in some situations for priming
3. CPD with adenine: the pump during cardiopulmonary bypass.
• The addition of small amounts of adenine (0.25-0.5mg) • Heparinized whole blood is used in open heart surgery to prevent
increases red blood cell survival of aiding synthesis, of ATP by cardiac abnormalities that might result from depression of ionized
the RBCs to 35 days. calcium levels by the citrate in other storage solutions.
4. ADSOL (AS-1) – 49 days • Heparin anticoagulant is not a RBC preservative because it lacks
• Adenine – glucose – mannitol – sodium chloride is a preservative glucose.
for the storage of packed red blood cells. Storage time – 49 • Its anticoagulant effect is also neutralized during storage by the
days. thromboplastic substances liberated by the cellular elements of blood
5. Nutricel (AS-3) during storage.
• Nutricel contains glucose; adenine; citrate; phosphate and • Blood stored in heparin must be used within 24 to 48 hours of
sodium chloride. With the addition of nutricel; the shelf life can be collection.
extended to 42 days. Saline = 140mmol/l; adenine = 1.5mmol/lʼ
glucose = 50mmol/l; mannitol = 30mmol/l.

• Changes that occur during storage of whole blood in CPD at 40C The recommendations of the ASA practice guidelines include:
Parameter Day 1 Day 7 Day 14 Day 21 Day 35 • Transfusion is rarely indicated when the Hb concentration is greater
than 10gm/dl and is almost always indicated when it is less than
↓ PH 7.2 7 6.9 6.84 6.73
6gm/dl, especially when the anemia is acute.
↓ 2,3 DPG (μm/ml) 4.8 7.2 1 1 <1 • The determination of whether intermediate Hb comes (6 to 10gm/dl)
↓ P50 (mmHg) 26 23 20 17 justifies or require red blood cell transfusion should be based on the
↑ K+ (mEq/l) 4 12 17 21 patients risk for complications of inadequate oxygenation.
• The use of a single haemoglobin “trigger” for all patients and other
↑ Hb (mg/dl) in plasma 1.7 7.8 13 19 46
approaches that fail to consider all important physiologic and surgical
↑ Blood PCO2 (mmHg) 48 80 110 140 factors affecting oxygenation are not recommended.
↓ Platelets (%) 10 0 0 0 0 • When appropriate, preoperative autologous blood donation,
intraoperative and postoperative blood recovery; acute normovolemic
↓ Viable cells 24 hrs 100 98 85 80
hemodilution and measures to decrease blood loss may be
after transfusion (%)
beneficial.
Parameters that decreases: • The indications for transfusion of autologous RBCs may be more
liberal than those for allogeneic RBCs because of lower risks
• pH (7.2)
associated with the former.
• P50 (26)
Recommendations:
• 2,3 DPG (4.8)
• Hb > 10 not indicated, < 6g/dl acute.
• Platelet cells % (10%)
• 6-10 g/dl à based on patients risk for complications of inadequate
• Viable cells 24 hrs later % (100%)
oxygenation.
Administrations of one unit of packed RBCs will increase hematocrit
Parameters that increases:
value by 3-5 percent. Indications are
• K+ (4)
1. Blood loss > 20 percent of blood volume
• PCO2
2. Haemoglobin < 8gm/dl
• Hb in plasma
3. Haemoglobin < 10gm/dl with major d/s eg. emphysema; IHD
Blood transfusion: 4. Haemoglobin 10gm/dl with autologous blood.
5. Haemoglobin < 12gm/dl and ventilator dependence
• Considerable morbidity and to a lesser extent mortality are
associated with blood transfusion therapy. Blood and blood
products should be transfused only when there are clear
therapeutic indications.
10

COMPATIBILITY TESTING: b) Incubation phase:

• Compatibility testing are designed to demonstrate harmful • Involves incubation of the 1st phase reaction at 370C in albumin or
antigen, antibody interactions in vitro so that harmful in vivo low ionic strength salt solution. The addition of these 2 aids in the
antigen-antibody interactions could be prevented. detection of incomplete antibodies or those antibodies that are able
• The ABO-Rh type, cross match and antibody screen are to attach to a specific antigen (sensitization) but unable to cause
frequently referred to as compatibility tests. agglutination in a saline suspension of red blood cells.
I. ABO-Rh typing: • This phase primarily detects antibodies in the Rh system. The
• Determination of ABO group and Rh of the recipient and donor is incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
the 1st step in selecting blood for transfusion therapy. ABO strength salt solution in this phase is of sufficient duration to allow
typing is performed by testing RBCs for the A and B antigens and antibody uptake sensitization by the cells so that incomplete
the serum for the A and B antibodies before transfusion. The only antibodies missed in this phase can be detected in the subsequent
additional required testing is that for the Rh (D) ag. About 85% of anti-globulin phase.
individuals possess the D antigen and are termed Rh(D) positive, c) Anti-globulin phase:
the remaining 15 percent, who lack the D antigen, are termed Rh • Involves the addition of anti-globulin sera to the incubated test tubes
(D) negative. with this addition, antihuman antibodies present in the sera become
II. Cross matching: attached to the antibody globulin on the red blood cells, thus causing
• A cross match is essentially a “trial transfusion” within a test tube agglutination. This phase detects most incomplete antibodies in the
in which donor RBCs are mixed with recipient serum to detect a blood group systems including the Rh, Kell, Kidd and Duffy blood
potential for series transfusion reactions. The cross match can group systems.
be completed in 45 to 60 mins and is done in three phases: an Types of cross match:
immediate phase; an incubation phase; and an anti-globulin Major cross match: is done when the donorʼs erythrocytes are
phase. incubated with the plasma of the recipient. Agglutination confirms that
a) Immediate phase: the plasma of the recipient contains antibodies to antigens on cell
• The immediate phase is conducted at room temperature. It membranes of donor erythrocytes.
detects ABO incompatibilities and those caused by naturally Minor cross match: is done when the plasma of the donor is incubated
occurring antibodies in the MN, P and Lewis systems. This takes with the erythrocytes of the recipient. Agglutination results if the
approx. 1 to 5 mins to complete. plasma of the donor contains antibodies to antigens on cell
membranes of recipient erythrocytes.
III. Antibody screening:
• This is also carried out in 3 phases and is similar in length to the
cross match. This test is conducted on recipient serum to rule out the
possibility of hemolytic transfusion reaction. It is also done on the
donor serum to detect unexpected antibodies in order to prevent their
introduction into the recipients serum or to prevent reactions between
transfused donor units.
11

2. Development of Red Blood Cells. Dr Azam’s Notes in Anesthesiology 2013
!
3*)%"#(&)*+#((
!"#$%"&'"(&)*+#(
!"'+#,-)'"($#..&( 45.2160'$2)#&(( DEVELOPMENT OF BLOOD CELLS:
'/()0#(-11%,#( 7',589(,',54((
• Blood cells develop from a small population of
&2&)#1( .2160'$2)#&(( TOTIPOTENT hematopoietic STEM CELLS which maintain
their numbers by self replication and also gives rise to
8:(;2160'$2)#&9( precursors of one or other of the various blood cells series
6.*&1*($#..&(( and cells of the immune system.
<=;>(?=!;@AB4@7C(
4D4@!D4=74(<4=3(
A=;;<(
="2)0"'-E(&#"-#&(F#"2)0"'$2)#&(( Bombay Blood group:

• Extremely rare ABO group
3#+*G*"2'$2)#(F(6.*)#.#)&((( • First discovered in Bombay
• Their red cell lack ABH antigen and their sera
3','$2)#&(F(1*$"'60*+#&(&#"-#&(F( containing Anti - A, Anti - B and Anti H.
1','$2)#&(*,E(1*$"'60*+#&(((( • The Anti H would not be detected in ABO group.
7#%)"'60-.&(&#"-#&(F(&#+1#,)#E((( Other Systems other than ABO:
(((((((((((((((((((((((((((((((7#%)"'60-.&((
C"*,%.'$2)#&(
• M & N system
• Kell System
='&-,'60-.(&#"-#&(F(&#+1#,)#E(( • Lewis system
(((((((((((((((((((((((((((((((='&-,'60-.&((( • Kidd - Zolinger
8*&'60-.(&#"-#&(F(&#+1#,)#E(((( • Duffy
(((((((((((((((((((((((((((((8*&'60-.&(((( • I = I & i antigen
• P - similar to ABO
H?'1*,'I&G2(&)*-,&(( • Lutheran
12

3. Blood Group system. Dr Azam’s Notes in Anesthesiology 2013
There are two Systems: ABO & Rh.

2) The Rh group:
1) ABO system:
• The Rhesus (Rh) blood group system was first demonstrated in
• A and B antigens are inherited as Mendelian humans, by the use of an antiserum prepared by immunizing
dominants, and individuals are divided into 4 major
rabbits with red cells from a rhesus monkey. It was found that
blood types on this basis.
some human red cells were agglutinated by the serum “Rh +ve
• Type A individuals have A ag on the RBCs cells” – while others were not – “Rh –ve cells”. This system is
• Type B individuals have B ag composed primarily of C, D and E antigens of which D is the
• Type AB individuals have both antigens most important antigenic component and the term “Rh positive”
• Type O individuals have neither means that the individual has the D antigen and “rh –ve” means
• Several subgroups of A exist; the most important that the individual has no D antigen.
being A1 and A2. • Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
• The difference between A1 and A2 appears to be system anti-D abs do not develop without exposure of a D –ve
quantitative. Each A1 cell has about 1,000,000 individual to D +ve red cells by transfusion or entrance of fetal
copies of the A ag on its surface and each A2 cell blood into the maternal circulation.
has about 250,000.
• The A and B antigens are found in many tissues in Bombay Blood group:
addition to blood these include salivary glands, • This is an extremely rare ABO group, called so because it was
saliva, pancreas, kidney, liver, lungs, testes, semen first discovered among some people in Bombay (now Mumbai).
and amniotic fluid. Although the group is more likely to occur in East Indians, it is a
• Antibodies against red cell agglutinogen are called very rare group even here.
agglutinins. • It is not restricted to East Indians but found in Caucasians,
• The serum of an individual contains antibodies Japanese, etc.
against the Ags lacking on the persons red cells. • Their red cells lack ABH antigens and their sera contain anti-A
Thus type A individuals develop anti B antibodies; and anti-B and anti-H.
type B individuals develop anti A abs, type O • The anti-H would not be detected in the ABO group but would be
individuals develop both, type AB individuals detectable in pre-transfusion tests.
develop neither.
13

4. Blood storage System. Dr Azam’s Notes in Anesthesiology 2013
1. Several different preservative solutions can CPD (citrate phosphate dextrose): – 28 days
be added to either whole blood or packed ! Trisodium citrate ! ! ! - 2.6gm /dl
RBCs to allow storage of these products. ! Citric acid ! ! ! - 0.327gm/dl
2. In general preservative solutions contain ! Sodium di hydrogen phosphate ! - 0.2gm /dl
additives that ! Dextrose ! ! ! ! - 2.55gm /dl
a. Prevent coagulation ! Water ! ! ! ! - 100 ml
b. Support glycolysis ! pH ! ! ! ! ! - 5.5
c. Maintain ATP generation • 63ml of CPD with 450ml of whole blood storage duration – 28 days
3. The preservative determines the blood 1. Citrate prevents clotting by binding calcium.
products storage on shelf life. The duration of 2. Dextrose allows continuation of glycolysis of RBC and thus maintains
storage is determined by the requirement sufficient concentrations of high energy ATP to ensure continued red
that at least 70% of the transfused red blood blood cell metabolism and subsequence viability during storage.
cells remain in circulation for 24 hrs after 3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts the large
infusion. fall in hydrogen ions that occur when the blood is cooled.
4. A unit of whole blood generally contains Other preservatives
450ml (± 10%) of blood and about 60ml of CPD with adenine: - 35 days
preservative. • The addition of small amounts of adenine (0.25-0.5mg) increases red
blood cell survival of aiding synthesis, of ATP by the RBCs to 35 days.
The various preservatives are: ADSOL (AS-1) – 49 days
ACD (acid citrate dextrose) - 21 days. • Adenine – glucose – mannitol – sodium chloride is a preservative for the
• Trisodium citrate = 2.2gm /dl storage of packed red blood cells. Storage time – 49 days.
• Citric acid = 0.8gm/dl
Dextrose = 2.5gm /dl Nutricel (AS-3): 42 days
•
• Water upto = 100ml • Nutricel contains glucose; adenine; citrate; phosphate and sodium
pH = 5.0-5.1 chloride. With the addition of nutricel; the shelf life can be extended to 42
•
67.5ml ACD is mixed with 420-450ml of blood days. Saline = 140mmol/l; adenine = 1.5mmol/lʼ glucose = 50mmol/l;
•
duration of storage = 21 days mannitol = 30mmol/l.
Frozen storage: 3 to 5 years
Preservatives: • RBCs previously frozen to -790C in glycerol can be thawed without
damage; but it must be free from glycerol before being transfused.
• Acid citrate dextrose (ACD) -21 days
Storage time - several years.
• Citrate phosphate dextrose (CPD) -28 days
• CPD + adenine – 35 days
14

Blood storage System.Continued Dr Azam’s Notes in Anesthesiology 2013
The advantages of frozen and thawed RBCs are the following: Changes that occur during storage of whole blood in CPD at 400C
1. Blood of rare types can be stored for long periods, Parameter Day 1 Day 7 Day 14 Day 21 Day 35
increasing viability and eliminating outdating.
↓ 1) PH 7.2 7 6.9 6.84 6.73
2. Frozen, reconstituted blood is believed to be safer in
patients who are especially susceptible to allergic reaction ↓ 2) 2,3 DPG (μm/ml) 4.8 7.2 1 1 <1
because the freezing and washing process reduces sites ↓ 3) P50 (mmHg) 26 23 20 17
with histocompatible antigens. ↑ 4) K+ (mEq/l) 4 12 17 21
3. Frozen blood, low in fibrin and leukocyte aggregates,
would be safer in patients requiring massive blood ↑ 5) Hb (mg/dl) in plasma 1.7 7.8 13 19 46
transfusion. ↑ 6) Blood PCO2 48 80 110 140
4. Frozen washed blood may reduce risk of transfusion (mmHg)
hepatitis. ↓ 7) Platelets (%) 10 0 0 0 0
5. Frozen RBCs may be desirable in clinical conditions ↓ 8) Viable cells 24 hrs 100 98 85 80
requiring prompt tissue oxygenation because normal levels after transfusion (%)
of 2, 3-DPG are retained in frozen erythrocytes.
Heparin: !
• Whole blood stored in heparin is used in some situations for
!"#$%&'(# @A#$1(#
priming the pump during cardiopulmonary bypass. )*+#$',(# )BC'#
• Heparinized whole blood is used in open heart surgery to '-.#/)0#$1&2(# "=#<D#!348E4###
prevent cardiac abnormalities that might result from )3456365#76338#9#$:+9(#
depression of ionized calcium levels by the citrate in other ;<4=36#76338#'1#>?8#3456?#
storage solutions. 9#$:++9(#
• Heparin anticoagulant is not a RBC preservative because it
lacks glucose. Its anticoagulant effect is also neutralized
during storage by the thromboplastic substances liberated
by the cellular elements of blood during storage.
• Blood stored in heparin must be used within 24 to 48 hours
of collection.
15

5. Recommendation of Blood transfusion. Dr Azam’s Notes in Anesthesiology 2013
BLOOD TRANSFUSION: Recommendations:

• Considerable morbidity and to a lesser extent mortality 1. Hb > 10 not indicated, < 6g/dl acute - Always Indicated.
are associated with blood transfusion therapy. Blood and 2. 6-10 g/dl à based on patients risk for complications of
blood products should be transfused only when there are inadequate oxygenation.
clear therapeutic indications. • Administrations of one unit of packed RBCs will increase
The recommendations of the ASA practice guidelines hematocrit value by 3-5 percent. Indications are
include: I. Blood loss > 20 percent of blood volume
I. Transfusion is rarely indicated when the Hb II. Haemoglobin < 8gm/dl
concentration is greater than 10gm/dl and is almost III. Haemoglobin < 10gm/dl with major d/s e.g. emphysema; IHD
always indicated when it is less than 6gm/dl, especially IV. Haemoglobin 10gm/dl with autologous blood.
when the anemia is acute. V. Haemoglobin < 12gm/dl and ventilator dependence
II. The determination of whether intermediate Hb
(6 to 10gm/dl) justifies or require red blood cell
transfusion should be based on the patients risk for
complications of inadequate oxygenation.
III. The use of a single haemoglobin “trigger” for all
patients and other approaches that fail to consider all
important physiologic and surgical factors affecting
oxygenation are not recommended.
IV. When appropriate, preoperative autologous blood
donation, intraoperative and postoperative blood
salvage; acute normovolaemic hemodilution and
measures to decrease blood loss may be beneficial.
V. The indications for transfusion of autologous RBCs
may be more liberal than those for allogeneic RBCs
because of lower risks associated with the former.
16

6. Compatibility Testing Dr Azam’s Notes in Anesthesiology 2013
• Compatibility testing are designed to demonstrate harmful • This phase primarily detects antibodies in the Rh system. The
antigen, antibody interactions in vitro so that harmful in vivo incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
antigen-antibody interactions could be prevented. strength salt solution in this phase is of sufficient duration to allow
• The ABO-Rh type, cross match and antibody screen are antibody uptake sensitization by the cells so that incomplete antibodies
frequently referred to as compatibility tests. missed in this phase can be detected in the subsequent antiglobulin
I. ABO-Rh typing: phase.
• Determination of ABO group and Rh of the recipient and c) Antiglobulin phase:
donor is the 1st step in selecting blood for transfusion • Involves the addition of antiglobulin sera to the incubated test tubes
therapy. ABO typing is performed by testing RBCs for the A with this addition, antihuman antibodies present in the sera become
and B antigens and the serum for the A and B antibodies attached to the antibody globulin on the red blood cells, thus causing
before transfusion. The only additional required testing is that agglutination. This phase detects most incomplete antibodies in the
for the Rh (D) ag. About 85% of individuals possess the D blood group systems including the Rh, Kell, Kidd and Duffy blood group
antigen and are termed Rh(D) positive, the remaining 15 systems.
percent, who lack the D antigen, are termed Rh(D) negative. Types of cross match:
II. Cross matching: • Major cross match: is done when the donorʼs erythrocytes are
• A cross match is essentially a “trial transfusion” within a test incubated with the plasma of the recipient. Agglutination confirms that
tube in which donor RBCs are mixed with recipient serum to the plasma of the recipient contains antibodies to antigens on cell
detect a potential for series transfusion reactions. The cross membranes of donor erythrocytes.
match can be completed in 45 to 60 mins and is done in • Minor cross match: is done when the plasma of the donor is incubated
three phases: an immediate phase; an incubation phase; and with the erythrocytes of the recipient. Agglutination results if the plasma
an antiglobulin phase. of the donor contains antibodies to antigens on cell membranes of
a) Immediate phase: recipient erythrocytes.
• The immediate phase is conducted at room temperature. It III. Antibody screening:
detects ABO incompatibilities and those caused by naturally • This is also carried out in 3 phases and is similar in length to the cross
occurring antibodies in the MN, P and Lewis systems. This match. This test is conducted on recipient serum to rule out the
takes approx. 1 to 5 mins to complete. possibility of hemolytic transfusion reaction. It is also done on the donor
b) Incubation phase: serum to detect unexpected antibodies in order to prevent their
• Involves incubation of the 1st phase reaction at 37 °C in introduction into the recipients serum or to prevent reactions between
albumin or low ionic strength salt solution. The addition of transfused donor units.
these 2 aids in the detection of incomplete antibodies or
those antibodies that are able to attach to a specific antigen
(sensitization) but unable to cause agglutination in a saline
suspension of red blood cells.
17

7. Blood Component therapy & Blood substitutes Dr Azam’s Notes in Anesthesiology 2013
• Except for conditions which result in acute haemorrhage, Diagrammatic scheme of how whole blood is separated for component
transfusion therapy is occasioned by the need to correct or therapy:
deficiency in a specific component of whole blood. The
rationale for component therapy stems from the recognition ! !"#$%& 5%6+,-789%& )$*+%$%+& 5%6+,-789%&: )$*+%$%+& 2,%%=%& 2*.+#,&3444&
that blood is a complex tissue with numerous constituents or '$##(& ,-."&/$*01*&& ;<<5& /##,&/$*01*& <
:>< 5& /##,&/$*01*&&
components, both cellular and noncellular, serving disease
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functions. Component therapy permits the physician to
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deliver an effective, therapeutic dose of the deficient
component with minimum risk of circulatory overload, or of )*.?%(&,%(& )$*+%$%+0&&&& 5,A#/,%.-/-+*+%&&&&&
adverse reactions to the administration of unnecessary blood .%$$&&& 2,%0"&
components. 2,%%=%& 7,#=%6& F<5&
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Blood components:
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.%$$0&&& /##,&,%(&.%$$0&&&&
1. Packed red cells
2. Leucocyte poor red cell I. Erythrocyte preparations:
3. Washed red cells i) Packed red blood cells:
4. Frozen red cells • The red cells from whole blood can be administered after removing
II. Leukocytes: 80% of the plasma. Packed red cells have a hematocrit of 60-90%.
1. Granulocytes • RBCs, rather than whole blood, should be used for the treatment of all
2. Mononuclear cells patients who require a transfusion because of a red cell mass deficit.
III. Platelets An absolute requirement for RBC exists, when transfusing anemic
IV. Plasma fractions: patients with actual or incipient congestive heart failure. RBCs are
1. Fresh frozen plasma administered in the same fashion as whole blood.
2. Platelet rich plasma • Packed red cells are prepared by centrifuging whole blood and is useful
3. Cryoprecipitate in RBC exchange in chronic anemiaʼs like thalassaemia.
4. Fractionated plasma ii) Leukocyte poor RBC:
o Factor VIII concentrate • Prepared during procuring blood or at the time of transfusion using
o Prothrombin complex concentration and factor IX specially designed filters.
concentrate • Other methods include sedimentation, inverted centrifugation filtration
o Albumin through nylon or cotton fibres, saline batch washing; frozen and thawed
o Immunoglobulin red cells or blood through microaggregate filters. Major indications for
o Antithrombin III concentrates using leukocyte poor red cells are:
1. To prevent non-hemolytic febrile reactions.
2. To prevent alloimmunization by HLA antigen in case of perspective
organ transplant cases.
3. To minimize or avoid transmission of CMV. 18
4. To prevent transfusion associated graft vs host disease (TA-GVHD).
Blood Component therapy & Blood substitutes.Continuation: Dr Azam’s Notes in Anesthesiology 2013
iii) Washed red cells: II. Leukocytes:

• Usually obtained from whole blood. Packed red cells • Less than 5% of the total body neutrophils pool is in the intravascular
obtained by centrifugation can be washed with saline using space. These cells have a half life of only four to ten hours in the
either manual batch centrifugation or continuous flow intravascular compartment and are therefore rapidly replaced. The
separator. Washed red cells should be used with in 24 hours collection of large number of granulocytes requires the processing of
after processing because of the risk of bacterial between 5 to 10 liters of blood per donation.
contamination (during processing). Washed red cells are i) Granulocytes:
also prepared from blood salvaged during surgery. The indications for granulocyte transfusion are not easy to define .In
Indications for washed red cells are general, the patient should have:
I. In patients who are hypersensitive to plasma. 1. An absolute granulocyte count < 500/ml
II. Who develop allergic or febrile reactions following whole 2. Fever
blood transfusion. 3. An unidentified microorganism
III. Multiple transfusion patients 4. No decrease in fever after 48hrs of antibiotic treatment.
IV. Saline washed red cells are also indicated in case of ii) Mononuclear cells:
neonatal transfusions to reduce the quantity of metabolic • Collection of blood stem cells come under this category. Stem cells are
breakdown products, extra-cellular potassium and the risk obtained for bone marrow transplant.
of CMV infusion. • Blood stem cells make up a very small part of the circulating
V. To avoid TA-GVHD mononuclear cell pool, cell separator techniques facilitate processing
Frozen red cells: large quantities of blood.
• After addition of a cryoprotective agent, RBC may be stored • Variety of substances like glucocorticoids, folinic acid, endotoxins help
continually below freezing temperatures. Freezing retards or release of stem cells into circulation, but the best currently used
arrests the deleterious biochemical changes which occur substance is human growth factor.
during liquid storage. Red blood cells can be frozen at -800C • Therapeutic use of peripheral stem cells is best cited in marrow
or below using 10% glycol as a preservative, and stored for transplantation; in cases like AML; Hodgkinʼs disease; multiple
3-5 years or even more. They are leukocyte poor and myeloma; solid tumors like Carcinoma breast, ovarian Ca,
relatively plasma free. neuroblastoma etc.
• Other advantages include availability of an inventory of rare
blood; promotion of component therapy; reduction in the III. PLATELETS:
incidence of non hemolytic reactions; a ready supply of i) Random donor platelets (RDP): 7-10 x1010 / unit
metabolically superior red cells; reduction in sensitization to • RDP is collected from routine donations of whole blood. Each platelet
histocompatibility antigens for potential transplant recipient bag contains 7-10 x 1010 platelets / unit. These platelets are suspended
and a reduced incidence of transfusion hepatitis. in 40-50 ml of donor plasma to be stored at 20-220C under constant
• However the technology is complicated and the whole agitation for 5 days. Also has leukocyte contamination.
process is expensive where one unit of frozen blood costs 3
times more than a unit of stored blood in liquid state.
19

ii) Single donor platelets: IV. PLASMA FRACTIONS:

• Prepared from single donor and each unit measures 1) Fresh Frozen plasma (FFP):
250-300ml. No significant WBC contamination & can be • FFP is the fluid portion of one unit of whole blood that is centrifuged,
stored at 220C under constant agitation for 5 days. separated & frozen solid at -180C or lower, to be transfused within 6 hrs
• One unit platelet concentrate will increase platelet count by of collection.
5000/mm3 to 10,000/mm3. • The initial volume of FFP transfused should be adequate to replace
deficient coagulation factors.
INDICATIONS FOR PLATELET TRANSFUSION: • The average adult usually requires two to nine units of about 200ml
1) Thrombocytopenia with decreased platelet production each given over a period of a few hours. The Prothrombin time (PT)
(Megakaryocyte thrombocytopenia) and / or partial thromboplastin time (PTT) should be determined
- Malignancy with cytoreductive therapy immediately before and after transfusion.
- Aplastic anemia 1. Plasma not frozen within 8 hours or thawed after freezing and not
- Myelodysplastic syndrome used within 24 hours has decreased levels of labile coagulation
2) Thrombocytopenia due to loss, destruction or sequestration factors V and factor VIII.
of platelets (megakaryocytic thrombocytopenia) 2. FFP contains factors IV, V, VII, VIII, IX along with naturally occurring
Platelet loss anticoagulants like protein C, protein S and also antithrombin III,
- Exsanguinations: replacement with stored blood electrolytes, albumin, Immunoglobulins and complement proteins.
- Cardiopulmonary bypass 3. Each unit of FFP prepared from a single unit of blood will have a
a. Platelet sequestration volume of 200-250ml and by Plasmapharesis can be upto 1 lit-1.5lit.
- Splenomegaly Indications of FFP:
- DIC 1. Coagulation factor deficiency [2, 5, 7, 9, 10, 11, 13]
b. Accelerated platelet destruction 2. Reversal of warfarin effect
- Idiopathic thrombocytopenic purpura; ITP 3. Massive blood transfusion
- Hereditary thrombocytopenia 4. Antithrombin III replacement
- Neonatal isoimmune thrombocytopenia 5. Thrombotic thrombocytopenic purpura
3) Qualitative platelet disorders 6. DIC
- Congenital 7. Coagulopathy of liver disease
- Acquired (myeloproliferative and myelodysplastic 8. Protein C or S deficiency
syndrome) 9. Hemolytic uremic syndrome
Dose of FFP: 1 unit for every 10 kg.
20

2) Cryoprecipitate: Replacement therapy for coagulation factor deficiency:

• Cryoprecipitate is prepared by thawing FFP at 40c and Factor Therapeutic dose Component / derivatives
removing the supernatant. Three major classes of plasma i) Fibrinogen 1 units / 5kg body Cryoprecipitate(100-250gms
derivatives are obtained from the cryoprecipitate ie ; wt fibrinogen/bag)
coagulation factors VIII and IX; immunoglobulin and albumin ii) Prothrombin 10-20ml plasma /kg Plasma or prothrombin complex
preparations. concentrate
• One unit of cryoprecipitate will have a volume of approx. iii) Factor V 20ml fresh frozen Fresh frozen plasma
plasma/kg
10-20ml and should contain 80-120 units of factor VIII and
iv) Factor VII 10-20ml plasma/kg Plasma or prothrombin complex
100-250ml of fibrinogen. concentrate
Indications: v) Factor VIII 15-50 units/kg Cryoprecipitate (100 units/bag) factor
1. Factors VIII and von Willebrand factor replacement. VIII concentrate
2. Fibrinogen replacement (a/dys/hypo-fibrinogenemia) vi) Factors IX 20-80 units/kg Prothrombin complex concentrate
3. Factor XIII replacement (↓ in trauma, burns and sepsis) plasma (1 unit of factor IX/ml)
4. Fibrin sealant – a combination of thrombin and vii) Factor X 10-20ml plasma/kg Plasma or prothrombin complex
cryoprecipitate. viii) Factor XI 10-20ml plasma/kg Plasma
5. Coagulum pyelotomy – a coagulum formed by the addition x) Factor XIII 4-6 bags Plasma or Cryoprecipitate
of thrombin and calcium to cryoprecipitate is used to entrap Cryoprecipitate or
calculi in the renal pelvis to facilitate pyelotomy removal. 500ml plasma
V. Albumin:
• The source material is whole blood plasma, serum or placenta. At least
96% of the total protein in the final product is albumin. The derivative is
available in 5% and 25% solutions. Plasma protein fractions containing
albumin and globulins are available for use as volume expanders. They
can be given without regard to ABO blood type. They are expensive
and are in short supply. They should be administered within 4 hours of
starting the infusion.
Indications:
1. Hypoproteinemia
2. Burns
3. Peritonitis
VI. Intravenous immunoglobulins:
Indications:
1. Viral infections: CMV
2. ITP
3. Post-transfusion purpura
4. Thrombotic thrombocytopenic purpura
21

VII. Antithrombin III concentrates: Blood substitutes:

• Antithrombin III deficiency • Some functions such as maintaining circulatory volume and oncotic
• Shock and DIC pressure can be replaced with various crystalloids and colloid
VIII. Factors VIII concentrates: macromolecules such as Dextrans and Hydroxyethyl starch.
• Used in treatment of hemophilia A Substitute Half life Reaction Mechanism
IX. Factor IX concentrates:
Dextran mol. wt 75,000 6 hrs Mild Allergic
• Used in treatment of hemophilia B
Hazards of component therapy: Mol. wt 40,000 2 hrs Severe Anti-dextran antibodies
• All hazards of blood transfusion are applicable to transfusion Gelatin 35,000 2-3hrs Immediate Histamine release
of components also: Starch 4,50,000 6 hrs Immediate Complement activation
Immediate reactions:
1. Febrile reactions
2. Allergic reactions These, however do not provide for oxygen transport.
3. Transfusion Related Acute Lung Injury - TRALI Red cell substitutes:
2 main indications:
4. Acute hemolytic transfusion reactions
5. Sensitivity to leukocytes and platelets • Severe haemorrhage
6. Non cardiogenic pulmonary oedema • Chronic symptomatic anemia for which no specific therapy exists.
7. Bacterial contamination • In both circumstances, the aim of red cell transfusion is to improve the
O2 supply to the tissues by raising the O2 content of blood according to
8. Bleeding syndrome
the equation.
9. Circulatory overload
O2 delivery = cardiac output x arterial O2 content
10. Air embolism
Delayed reactions: Arterial O2 content = Hb conc. x % saturation x 1.34
Oxygen Flux = Cardiac output x Hb x % saturation x 1.34 !
1. Delayed hemolytic reactions
(variables are CO, Hb, saturation)
2. Post transfusion purpura
Perfluorocompounds:
3. TA-GVHD
• Perfluorochemical are large organic compounds in which all the
4. Transmission of diseases like hepatitis B, hepatitis C,
hydrogen atoms are replaced by fluorine. A unit volume of
HIV, CMV, HTLV-3 etc.
perfluorochemical carries almost three times the oxygen carried by a
similar volume of blood. They are chemically inert and not metabolized,
but require emulsification with surfactants to be miscible with blood.
i) Fluosol-DA:
• A 20% emulsion of 2 different Perfluorocompounds described as
FLUOSOL-DA which has O2 carrying capacity at 370C of about 40% of
that of red cells.
Dose: 20ml/kg
Side effects:
• Pulmonary reactions; cytotoxicity; complement activation; retention of
the product in the liver and spleen and vulnerability to oxygen 22
toxicity.

ii) Polyfluoro-octobromide (Perflubron):

• It is a newer Perfluorocompounds (radiopaque)
• Has 2 advantages
• Higher concentration of the compound can be administered
because 100% emulsion with a phospholipids has a sufficiently
low viscosity to be infused without dilution.
• O2 is more soluble in perflubron
• It can carry as much O2 as a Hb solution at a conc. of 7gm/dl.
Conclusion:
• Red cell substitutes under trial have too short a survival time in
circulation to be substitutes for red cell in treatment of chronic
anemia.
• They can be used in short term procedures, such as immediate
resuscitation and in intra operative haemodilution, red cell has
to be transfused within next 24 hrs.
23

8. Define Massive blood transfusion. Discuss the complications associated with massive blood
transfusion.
Definition:
• Massive blood transfusion may be defined either as the acute administration of more than 1.5
times the patients total blood volume by homologous blood in less than 24 hours.
Also defined as:
• Transfusion of one pint of blood with in 5 minutes;
• Transfusion of 5 units within 1 hr
• Transfusion of 10 units within 6hrs,
• Transfusion of >10% of blood volume within 10 minutes.
Complications of Massive Blood transfusion:
Early
Late
• Hemolytic reactions
! Immediate • Transmission of infection
! Delayed ! Viral (hepatitis A, B, C, HIV, CMV)
Non-hemolytic febrile reactions ! Bacterial (Salmonella), Parasites (Malaria,
•
Allergic reactions to proteins, IgA Toxoplasma)
•
• Transfusion-related acute lung injury • Graft-vs-host disease
• Reactions secondary to bacterial contamination Circulatory • TRIM - Transfusion related immunomodulation
overload • Iron overload (after chronic transfusions)
• Air embolism • Immune sensitization (Rhesus D antigen)
• Thrombophlebitis
• Hyperkalaemia
• Citrate toxicity
• Hypothermia
• Clotting abnormalities (after massive transfusion)
24

Complications of Massive Blood transfusion: Dr Azam’s Notes in Anesthesiology 2013
Early
• Clotting abnormalities (after • Citrate toxicity:↓ in

• Hemolytic reactions ionized calcium
massive transfusion)
- Immediate
- Delayed
A massive transfusion of red blood

cells (RBCs) may lead to a Citrate binds calcium, thus lowering the
The most serious complications of blood ionized plasma calcium concentration.
transfusion result from interactions • Dilutional Coagulopathy,
• Consumptive coagulopathy, This is usually prevented by rapid hepatic
between antibodies in the recipientʼs metabolism unless the patient is
plasma and surface antigens on donor • Thrombocytopenia.
hypothermic
RBCs. - Incompatible blood
Treatment
Treatment
• Calcium gluconate 10ml 10% over 10 min
Signs and symptoms of • is less effective than calcium chloride
hemolytic transfusion reaction: • Administration of platelets and FFP because it must be metabolized to be
• Fever and chills • Dose: 1 Unit of FFP for every 10 kg effective.
• Chest pain • 2 unit FFP for each 10unit of blood transfused • 13.4% calcium chloride containing calcium
• Hypotension • 6 unit Platelet concentration for every 20u of 0.192 mmol/ml is more effective than the
• Nausea blood transfused weaker 10% calcium gluconate solution which
• Flushing • Basic screening tests for bleeding after surgery-- contains only 0.22mmol/ml of calcium.
• Dyspnoea Platelet count; prothrombin time; APTT; plasma
• Hemoglobinuria fibrinogen concentration and fibrinogen
degradation products when indicated. • Massive transfusion with PRBC alone causes
a dilutional coagulopathy.
Treatment of Hemolytic reaction: • Massive hemorrhage causes consumptive
I. Stop the transfusion coagulopathy.
II. Maintain the urine output at a minimum of 75-100ml/hr
III. Alkalinize the urine
1. Send patient blood and urine sample to blood bank for examination.
2. Prevent hypotension to ensure adequate renal blood flow.
3. Maintain IV line, O2 therapy; resuscitative measures.
4. Antihistamine – diphenhydramine 0.5-1mg/kg IV.
5. Steroid – hydrocortisone – 2-4mg/kg IV. 25
6. Antibiotics
Complications of Massive Blood transfusion: Continuation Dr Azam’s Notes in Anesthesiology 2013
Early
• Hypothermia: • Transfusion-related acute lung injury
• Hyperkalemia: • Acid-base disturbances: RBCs are stored at 4 °C. Rapid • Occurs during or within 6 hours of
transfusion at this temperature will transfusion.
quickly lower the recipientʼs core • Two different mechanisms for the
Each unit of RBCs
temperature and further impair pathogenesis of TRALI :
contains 1–2mmol of
haemostasis. Hypothermia reduces • Immune (Antibody mediated)
The potassium acid. This is generated
the metabolism of citrate and lactate • Non-immune.
concentration of blood from the citric acid of the
and increases the likelihood of • Immune TRALI results from
increases during storage, anticoagulant and from
hypocalcaemia, metabolic acidosis the presence of leucocyte
by as much as 5– the lactic acid produced
and cardiac arrhythmias, Peripheral antibodies in the plasma of
10mmol. After during storage;
coagulopathy, vasoconstriction, donor blood, directed
transfusion, the RBC metabolism of this acid is
Infection. against human leucocyte
membrane Na+–K+ usually very rapid.
ATPase pumping antigens (HLA) and human
Treatment: Treatment: neutrophil alloantigens
mechanism is re-
• Adequate fluid • This reduction in temperature can (HNA) in the recipient.
established and cellular be minimized by warming all IV
potassium re-uptake resuscitation
• At times may • Fluids and by the use of forced air
occurs rapidly. convection warming blankets to
require
Bicarbonate reduce radiant heat loss.
• Transfusion of therapy • Reduction in coagulation factors for
> 7 units of each 1 °C, drop in temperature.
PRBCs, • CT is prolonged below 33 °C.
associated with Note: • Increase room temperature.
independently • 10% reduction in • Surface waring the patient with
increases
coagulation for 1 °C heating blanket, heating lamps.
potassium.
drop in • Heated & humidified inspiration
temperature. gases.
• Using blood and fluid warmer.
26

Complications of Massive Blood transfusion: Continuation Dr Azam’s Notes in Anesthesiology 2013
Late:
• Transfusion-associated
•Transfusion-related infections • Immunomodulation
graft-vs-host disease:
Bacterial The potential to modulate the
Bacterial contamination of blood components immune system of transfusion
Transfusion-associated graft-vs- recipients remains an exciting
is an infrequent complication of transfusion. host disease (GvHD) is a very rare but controversial area of
• Brucella complication of blood transfusion
• Pseudomonas transfusion medicine.
• Salmonella
• Shigella
Viral • Non-haemolytic febrile reactions
The incidence of transfusion-related viral These reactions are very common and are usually not life-threatening. Reactions
infection has greatly reduced result from donor leucocyte antigens reacting to antibodies present in the recipient’s
• Cytomegalovirus (Incidence 1:10 to 1:30) plasma.
• Hepatitis • Allergic reactions
• HIV (Incidence 1:50000) Allergic reactions are common and usually mild. The majority are due to the
• Epstein barr virus presence of foreign proteins in donor plasma and are IgE-mediated. Pruritus and
• Herpes simplex urticaria, with or without fever, are the most common features. The transfusion
• Measles should be stopped and antihistamines administered.
Parasites:
Treatment is he same as for anaphylaxis from other causes, with IV fluid
• Malaria resuscitation, epinephrine administration (to reestablish vasomotor tone and reverse
• Toxoplasmosis bronchospasm), antihistamines, corticosteroids and respiratory support. If
subsequent transfusions are required in such patients, washed RBCs should be
Incidence: used (residual plasma and therefore IgA is removed).
• HCV = 1:30,000 to 40000
• EBV = 1:200
27

9. Describe Anesthetics concerns for regional anesthesia in a patient on anticoagulants.
• Guidelines based on literature, case studies, and consensus statements .

• The morbidity of spinal hematomas can be greatly reduced with early diagnosis and intervention.
• Neurological monitoring at least every 2hrs should be considered in high-risk situations.
• Consider using neuraxial infusions with low doses of local anesthetic in higher risk situations.
• This will enhance early detection of spinal hematoma
• Combined therapies, which attack unique components of the coagulation cascade, may increase the risk of bleeding complications. (e.g. Heparin AND coumadin)
• Approach new agents affecting coagulation with caution.(e.g.Fondaparinux)
Regional anesthesia in a patient on anticoagulants - ASRA
• Thrombolytics
• Heparin- Unfractionated • Low Molecular
Weight Heparin
• Consider avoiding neuraxial (LMWH)
Subcutaneous Heparin
blocks, except in extreme
circumstances. Time block at • No contraindication for neuraxial techniques
with mini-dose SQ heparin High Dose-BID LMWH
least 10 days after, and 10 days
before thrombolytics given. • Time insertion of needle or removal of (e.g. enoxaprin 1mg/kg q12hr, or 1.5mg/
catheters 4 hours after last dose, and 2-4 kgQD) !
• If thrombolytics are given
hours before subsequent dose. • First dose should be given >24hrs after
around the time of neuraxial
puncture, monitor patients at • Consider checking a platelet count in patients the block, and 2 hrs after catheter
receiving SQ heparin for greater than 4 days, removal
least Q2hrs, and use solutions
to rule out heparin-induced thrombocytopenia • Indwelling catheters should be removed
with weak local anesthetic.
(HIT.) prior to initiating therapy
• No recommendation for timing Low dose intra-operative heparin LowDose-QDLMWH
of catheter removal after
• Delay heparin dose for 1 hr after needle (EuropeanRegimen)
unexpected thrombolytics use.
placement. Remove catheter 1 hr before any
• Use caution and consider • Indwelling neuraxial catheters can be
subsequent dose, or 2-4 hrs after last dose. safely maintained.
checking fibrinogen levels.
E.g: • Consider postoperative monitoring (q2hr • First dose of LMWH should be given 6-8
neuro checks) and using weak local hrs after block.
• Alteplase
anesthetic concentrations.
• Reteplase • Catheter should be removed >10-12 hrs
Prolonged therapeutic heparinization
• Streptokinase after the last dose. o!Subsequent dose of
• Neuraxial blocks should be avoided in this LMWH given >2 hrs after removal of
• Urokinase
situation catheter.
28

Regional anesthesia in a patient on anticoagulants Dr Azam’s Notes in Anesthesiology 2013
• Fondaparinux
• Coumadin/Warfarin: • Anti-platelet Medications
• Anti-thrombotic effect through factor Xa

• Chronic oral anticoagulation should be • Includes NSAIDS inhibition, actual risk unknown.
stopped 4-5 days prior to block, and PT/ (motrin,naproxen),thienopyridines(ticlopidine • Consensus recommendations based on the
INR checked before procedure and clopidogrel), glycoprotein IIb/IIa sustained and irreversible anti thrombotic effect,
performed. antagonists (abciximab, tirofiban) early postoperative dosing, and report of spinal
• If initial dose given >24 hrs prior to • Bleeding time not a reliable test. Risk for hematoma reported during initial clinical trials.
procedure,or if 2 or more doses given, bleeding increased in females, elderly, and • Recommend single needle pass, atraumatic
check PT/INR before block. those with a history of easy bruising/ needle placement, and avoidance of indwelling
• Catheters can be safely maintained on excessive bleeding. neuraxial catheters
low dose (5mg) warfarin therapy • NSAIDS-no added risk or timing concerns
CheckPT/INR QD for indwelling catheter for neuraxial techniques when used alone.
in pts on warfarin Ticlopidine,clopidogrel, and platelet GP
• If INR > 3, with hold or reduce coumadin antagonist may represent significant risk:
Herbal Preparations:
dose. • Ticlopidine- discontinue 14 days prior to Of concern to the anesthesia provider is the side
• Catheters can be removed when INR < block Clopidogrel- discontinue 7 days prior
effect of bleeding in the patient who consumes
1.5. to block
herbal preparations.
• Minimize local anesthetic concentration; • Abciximab- discontinue 2 days prior Mechanism of action: varies with the preparation.
monitor neuro status during therapy and • Eptifibatide and tirofiban- discontinue 8hrs
• Garlic, ginger, feverfew: inhibit platelet
for 24hrs after catheter removal prior to block (GPIIb/IIIa)
aggregation
Cox-2selective inhibitors(rofecoxib, celecoxib,
• Ginseng: antiplatelet components
valdecoxib)
• Alfalfa, chamomile, horse chestnut, ginseng:
• Minimal effect of platelet function. contain a coumadin component
• Consider in patients requiring anti-
• Vitamin E: reduces platelet thromboxane
inflammatory peri-operatively.
production
• Ginko: inhibits platelet activating factor
The risk for epidural/spinal hematoma is unknown. Surgical
patients should be advised to stop herbal products 5-7 days
before surgery. One of the crucial aspects of preoperative
assessment is the concomitant use medications that alter
coagulation. In addition, the patient should be screened for
bleeding tendencies
29

10. What is Disseminated intravascular coagulation? Enumerate its causes and management. Dr Azam’s Notes in Anesthesiology 2013
Disseminated intravascular coagulation (DIC), also known as disseminated intravascular coagulopathy

or consumptive coagulopathy, is a pathological activation of coagulation (blood clotting) mechanisms
that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside
the blood vessels throughout the body
Pathophysiology of DIC:
Stimulus
Tissue destruction Endothelial Injury
Tissue factor
Factor XII activation (Intrinsic pathway)
Extrinsic pathway
Thrombin generation
Platelet consumption
Intravascular fibrin deposition
Plasminogen activation
Thrombocytopenia
Thrombosis Clotting factor Bleeding

Plasmin generation
degradation
RBCʼs Tissue Ischemia Fibrinolysis Decreased

Damaged
circulating Decrease O2
blood transport
Fibrin degradation products (inhibit

thrombin & platelet aggregation)
Hemolytic anemia Tissue Hypoxia
ORGAN FAILURE
30

Enumerate its causes and management. Continuation: Dr Azam’s Notes in Anesthesiology 2013
Causes
for DIC
Infection: Obstetric: Malignancy: Traumatic: Intravascular Hemolysis:

• Septicemia • Pre-Eclampsia • Acute promyelocytic • Polytrauma with shock • Snake Venom
• Viremia • Placental abruption leukemia • Burns • ABO transfusion reaction
• Fungaemia • Amniotic fluid embolism • Metastatic carcinoma • Fat embolism
• Protozal • Retained products of • Neurosurgery
conception
• Placenta praevia
Treatment & Management of DIC:
• Treat the underlying cause
Clinical Features: S/S • Provide supportive management of complications
• Bleeding or bruising - from GI Tract, • Support organ function
genitourinary tract, ecchymosis,petechiae, • Stop abnormal coagulation and control bleeding by replacement of depleted blood and
purpura. clotting components (FFP,Platelets,PRBC)
• Laboratory findings: Thrombocytopenia, • Medications can be used and choice depends on the patientʼs condition (Heparin,
anemia, prolonged PT aPTT & FDP, Antithrombin III (ATIII), Fibrinolytic inhibitors)
Deranged D-DIMER. Plasma therapy
Investigation: Abnormalities of Lab DIC: Indications
• Increase PT, aPTT • Active bleeding
• Decrease platelets • Patient requiring invasive procedures
• Smear = Schitocytes • Patient at high risk for bleeding complications
• Decrease in Fibrinogen Fresh frozen plasma(FFP):
• Decrease in Factor V • Provides clotting factors, fibrinogen, inhibitors, and platelets in balanced amounts.
• Decrease in Factor VIII • Usual dose is 10-15 ml/kg
• Increase in D-DIMER Platelet Therapy:
Indications
• Active bleeding
• Patient requiring invasive procedures
• Patient at high risk for bleeding complications
• Platelets
• approximate dose 1 unit/10kg
• Cryoprecipitate = 1U/10 kg
• Fibrinogen concentrate = 2 - 3 gms
31
Enumerate its causes and management of DIC. Continuation: Dr Azam’s Notes in Anesthesiology 2013
Treatment & Management of DIC: Peri-operative Anesthetic implications & Management:

Blood Therapy: • Coagulopathy - CI for regional anesthesia
• Replaced as needed to maintain adequate oxygen delivery. • General anesthesia is preferred
• Blood loss due to bleeding • Invasive cardiovascular monitoring required - ABP,CVP
• RBC destruction (hemolysis) • Large bore IV lines for rapid transfusion
Coagulation Therapy: • Naso-tracheal intubation to be avoided
• Antithrombin III • Blood, platelet concentrate,FFP & Cryoprecipitate should
• Protein C concentrate be transfused promptly, bleeding parameters needs to be
• Tissue Factor Pathway Inhibitor (TFPI) measured regularly
• Heparin
Antithrombin III: Post-operative management:
• The major inhibitor of the coagulation cascade • Patients to be managed in ICU
• Levels are decreased in DIC. • May require mechanical ventilation
• Anticoagulant and anti-inflammatory properties • Hypothermia to be avoided
• Therapeutic goal is to achieve supranormal levels of ATIII • Antibiotics to be continued
(>125-150%). • Frequent measurement of PT,PTT & INR to be done.
Recombinant Protein C: Note:
• Inhibits Factor Va, VIIa and PAI-1 in conjunction with • Epsilon Amino Caproic Acid and fibrinogen should not be
thrombomodulin. administered in presence of continuing intravascular
• Protein S is a cofactor coagulation. EACA would inhibit secondary fibrinolysis
which is an intrinsic protective mechanism in patients with
Preoperative preparation: persistent DIC.
• Antibiotics for infection
• Hypovolemia to be corrected
• Warm fluids & Blood products
• Evacuation of retained products of conception
• Blood product to given based on the laboratory
investigations
• Coagulopathy corrected with FFP & platelets
• If fibrinogen level < 1gms/liter - Cryoprecipitate to be
transfused
• Adequate blood & blood products to be available before
surgery
• Recombinant protein C - in severe sepsis
• Intra-muscular injections to be avoided
32

11. Enumerate the indications of packed red cells, fresh frozen plasma(FFP), platelets
& cryoprecipitates.
A. Packed Red Cells: FFPʼs Continued:

Indications of Packed red cell: Product
• Deficient oxygen caring capacity or tissue hypoxia, due to • Anticoagulated plasma in frozen state
inadequate circulating red cell mass
Characteristics
• Exchange transfusion in hemolytic disease of new born or
in Sickle cell anemia Volume: 200-250 ml (= 1 unit)
Contains all plasma proteins
• Hypovolemia secondary to hemorrhagic shock.
Pharmacological Effect
Description of Packed red cells: Increase plasma clotting factors and prevent or stop
bleeding
• 150 to 200 ml red cells from which most of the plasma has
been removed
Dose of FFP:
• Hemoglobin approximately 20 g/100 ml ( not less that 45 g/
10 - 15 ml/Kg
unit)
• Hematocrit 55 to 75%.
C. Cryoprecipitate:
B. Fresh Frozen Plasma: Deﬁni&on: IT IS THE INSOLUBLE PORTION OF PLASMA REMAINING AFTER THE FRESH
Indications of FFPʼs: FROZEN PLASMA HAS BEEN THAWED BETWEEN 4°C TO 6°C. Increase plasma levels
• Congenital factor deficiency of high molecular weight clotting factors
• Invasive procedure or trauma ( e.g. factor XI deficiency)
• Emergency warfarin reversal Indications of Cryoprecipitate:
• Acquired bleeding disorders with active bleeding or prior to • Hemophilia A
an invasive procedure. (liver disease; vitamin K deficiency; • Von Willebrandʼs disease
disseminated intravascular coagulation; dilutional • Congenital or acquired fibrinogen deficiency
coagulopathy). • DIC
• Microvascular bleeding & elevated PT/PTT • Massive transfusion with dilutional hypofibrinogenemia
• Loss of more that one blood volume & no lab values then • Hypofibrinogenemia: Fibrinogen < 100 mg/dL with active bleeding or fibrinogen
give empirically. < 200 mg/dL in a postoperative patient with excessive bleeding.
• FFP is indicated in massive transfusion with demonstrated • Uremia or hereditary platelet disorder
deficiency of factor VIII & V • Factor XIII Deficiency
• Exchange transfusion in neonates. Composition:
• Volume: 5 - 15 ml (= 1 Unit; 1 BAG)
• Contains high molecular weight glycoproteins such as fibrinogen (300 mg/unit);
Factor VIII (80-100 U/unit); von Willebrand factor; factor XIII
Dose:
• 1 unit/10 Kg wt; Frequently 10 BAGS 33

Enumerate the indications of packed red cells, fresh frozen plasma(FFP),
platelets & cryoprecipitates. Continuation:
D. Platelets:
Indications of Platelets:
• Thrombocytopenia
• Platelet function defect
• Microvascular bleeding in surgical or obstetric patients
• Dengue fever
• Massive blood transfusion
Characteristics:
Whole Blood Apheresis
Donation Donation
Potency 5-8x 1010 40 x 1010
Volume (ml) 35 - 60 180 - 400
Labeling Platelets Platelets, pheresis
Common Usage Random Donor Single Donor Unit

Units
Platelets increased by 5000 - 7000 60,000 to 70,000
Doses of Platelets:
• 1 unit/10 Kg weight; 4 units/m2 Surface Area
• 1 Platelets, Apheresis
34

12. Write the blood conservative strategies in a 20 year old female scheduled Dr Azam’s Notes in Anesthesiology 2013
for excision of angiofibroma of nose?
Blood conservative strategies are getting great clinical relevance due to • Surgical hemostasis is done using bone wax & surgicel
the concern in transfusion allogenic blood. This is done to avoid • Local hemostatic agents such as: fibrin spray, application of
potential risk associated with blood transfusion. platelet gel before wound closure, topical use of Tranexemic
acid.
Methods of reducing blood transfusion/Method for blood • Systemic hemostatic agents Tranexemic acid,
conservation strategies are: desmopressin,aprotinin
• Tranexemic acid ( synthetic fibrinolytic inhibitor) reduces
1. Optimization of the preoperative hemoglobin: bleeding
• Preoperative Hb is best predictor of the need for allogenic transfusion • Initial bolus dose 10 mg/kg Max of 30 mg/kg/day
• If Anemia due to Iron deficiency - oral iron is prescribed. If it is not • Pneumatic tourniquet
effective intravenous administration of iron-sucrose can be done.
• If anemia not due to iron or Vit B12 deficiency or absence of chronic 3. Lowering the transfusion trigger:
blood loss then Hb & HCT will improve with administration of • The transfusion trigger of 10gm/dl & HCT of 30% can be safely
erythropoietin combined with iron supplement. be lowered in most patients without any cardia or respiratory
• Erythropoietin Regimen: co-morbidities.
• 300U/kg for 15 days beginning 10 days before surgery or • 8 gm/dl in older without any co-morbidity & 7 gm/dl in younger
• Weekly administration of 600 U/kg starting 3 weeks before surgery healthy patients
• Erythropoietin should always be combined with iron
supplementation. 4. Strategies in optimization of use of patients own blood:
Can be done by
2. Strategies to decrease perioperative blood loss / Reduction of • Acute isovolemic hemodilution: blood has low HCT which
blood loss: reduces RBC loss. It enhances microcirculation.
• Any congenital or acquired bleeding disorders should be detected • Autologus blood donation & transfusion: It should be targeted
• Aspirin & NSAIDS to be stopped 1 week before surgery to men with Hb of 11 to 14 gm/dl & to women with level of 13 to
• Patients of LMWH, Vit K antagonist & aspirin should be stopped 14 gm/dl, whose blood loss is close to 1000 ml.
before surgery. • Perioperative blood salvage:
• Position of the patient affects intraoperative bleeding: • Re-infusion of blood drained within 6 hours after operation
• Lateral position in THR decreases blood loss using cell salvage.
• Elevation of lower limbs after TKR reduces post operative blood • It is generally accepted that no more than 1000 ml of
loss drained blood be re-infused & not more than 6 hours after
• Controlled hypotensive spinal or epidural anesthesia using adjuvants end of surgery should not be transfused.
like clonidine neuraxially decreases blood loss • Contraindicated in patients with infection & malignancy.
• Maintaining normothermia decreases bleeding.
• Preoperative arterial embolization for complex pelvic fractures or
highly vascular tumors
35

Write the blood conservative strategies in a 20 year old female scheduled for excision of angiofibroma
of nose? Continuation:
Use of Blood Substitutes: Two types

of blood substitutes are available:
Perflurocarbons: Hb based o2 carriers:

• They are biologically inert volatile fluids • These are based on natural or
with high dissolving capacity for o2 & CO2 recombinant human Hb or bovine Hb
• They transport & deliver O2 by simple • produced by purification, encapsulation in
physical dissolution synthetic phospholid.
• Not water soluble • Side effect:
• their O2 carrying capacity depends on the • Increased Blood pressure due to
concentration of perflurocarbons which increased systemic vasoconstriction
varies between products. due to scavenging of nitric oxide &
• H+ atoms are replaced by fluorines oxidation which generated Meth Hb.
• One unit of perflurocarbons carry 3 • Short intravascular half life
times O2 carried by similar volume of • hence used in emergency situation.
blood
• Fluosol - DA : 20 % emulsion of 2
different compounds. Dose = 20ml/kg
• Polyfluro-octobromide: O2 solubility is
more
36

13. Autologus Blood transfusion. Dr Azam’s Notes in Anesthesiology 2013
II. INTRAOPERATIVE BLOOD SALVAGE:

Definition: Autologous blood transfusion is one in
• Pre-deposit donation is limited by the time that the blood can be
which both donor as well as recipient are the same. stored and by the ability of patients to donate at frequent intervals.
Types of autologous blood transfusion: The main steps of this technique are
1. Salvaging the blood from the operative site.
I. Preoperative blood donation 2. Anticoagulating the whole blood – prior to surgery and during
II. Intraoperative blood salvage suction.
III. Postoperative blood salvage 3. Re-infusing whole blood as such after filtering or re-infusing the
IV. Isovolemic hemodilution red cells after washing.
There are three basic methods for IBS:
I. PREOPERATIVE BLOOD DONATION: 1. Semi continuous flow centrifugation
2. Canister collection
Criteria:
3. Single use disposable reservoirs
• The haemoglobin > 11gm/dl
• The haemoglobin never below 10gm/dl. 1. Semi continuous flow centrifugation:
• Blood is aspirated, using a double lumen sucker, into a reservoir.
Contraindications: • The blood is washed, with saline prior to being re-infused.
• Active bacterial infection • Two varieties of equipment available, the so called
• Cardiac disease • slow flow machines which produce one unit every 7-10 mins
• Loss of consciousness • Fast flow system which produce a unit in less than 3 mins.
• Impaired placental blood flow – HTN, PET, DM
• COPD - Emphysema
2) Canister collection:
Method: • Aspirated, via a double lumen sucker
• 450ml of blood at weekly intervals. • Allows anticoagulant to be mixed at the sucker tip, through a
170μm filter into a rigid reservoir containing a disposable liner.
• Last donation 4 days before surgery
• Preferably 1 week prior to surgery.
• Should commence oral iron prior to their first
donation and continue until the day of surgery.
37

Autologus Blood transfusion. Continuation: Dr Azam’s Notes in Anesthesiology 2013
1) Single use Disposable reservoirs: INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:

• Blood is aspirated using a vacuum pressure of less than • Cardiovascular:
150mm Hg • Vascular surgery:
- Aortic aneurysm
• Anticoagulated prior to surgery, - Aortic rupture
• Anticoagulated using citrate. • Orthopedic: Hip and spinal surgery
• Re-infused by gravity using microaggregate filter, • Liver transplantation
• stored until room temperature, until required. • Neurosurgery
Advantage – cheap and requiring no specialized • Trauma
equipment or specially trained personnel. • Plastic surgery
• Jehovahʼs witnesses
Disadvantage – slow, small volumes, unwashed and has
• Serological antibodies:
a low hematocrit.
Precautions: Contraindications:
Avoid hemolysis: • Infections, sepsis, bacteremia
• The sucker should have a plastic tip with multiple holes • Blood containing significant amounts of amniotic fluid
• Turbulence to be avoided should not be auto transfused.
• pressure to be below 150-‐200 mmHg. • Blood containing:
• wound irrigants Betadine;
Anticoagulants: • methylmethacrylate,
• Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration • antibiotics
of 30,000 units per lt of saline, with 15ml of heparin /
saline being added to each 100 ml of blood (ratio heparin
to blood, 1:7).
Wash solution:
• The volume of saline wash solution should be three to four
times that of the volume of the blood, although for
orthopedic cases this may be increased to six to seven
times with a minimum volume of 150ml.
38

COMPLICATIONS FOR INTRAOPERATIVE CELL SALVAGE: IV. ACUTE NORMOVOLAEMIC HEMODILUTION/Isovolemic:

1) Air embolism • Definition: It indicates dilution of the blood while keeping the circulating
2) Re-infusion of hemolyzed red cells: blood volume constant.
! If the vacuum pressure on the sucker is too high or • HCT is used
excess turbulence has been caused by improper Contraindications to acute normovolaemic hemodilution:
aspiration technique, hemolyzed red cells can be re- 1. Hematocrit less than 24%.
infused into the patient. 2. Valvular heart disease and intra or extra cardiac shunting.
3) Coagulation disorders 3. Respiratory insufficiency needing mechanical ventilation.
4) Thrombocytopenia
4. Haemostatic defects.
5) Hypocalcaemia
7) Toxic antibiotic effects Compensatory mechanisms during hemodilution:
8) Microfibrillar collagen haemostatic material • Blood Rheology: Decreased viscosity & decreased oxygen carrying
capacity
III. Post operative blood Salvage: • Utilization of O2:
Used in: • Increased blood flow to the tissue
• CTVS • Increased oxygen extraction
• Joint replacement • Autonomic effects
• Trauma - chest wall & abdomen Effect on organ systems:
• Vacuum pressure = 0 - 40 mm of Hg i) Cardiac: Increased CO, Increased Coronary blood flow, Coronary
• Time between start of collection & re-infusion should be
Vasodilation.
< 4 hours.
Product has: ii) Cerebral: Increased Cerebral blood flow
• No clotting factors iii) Hepatic and gastrointestinal: Increased Hepatic blood flow,
• HCT 15 - 20 % Increased oxygen extraction
• Free Hb iv) Renal: Decreases renal blood flow
v) Pulmonary: Hemodilution does not alter pulmonary function
Complication: vi) Pregnancy: Hemodilution should be used with caution in pregnant
• Products of clot lysis Volume > 800 ml of unwashed patients, may result inadequate oxygen content in the blood perfusing the
blood are re-infused.
placenta.
• Upper airway oedema requiring intubation
• Non-cardiogenic pulmonary oedema
39

Methods:
• Crystalloids: 3:1 crystalloids to blood ratio.
• Colloids: 1: 1 Colloid to blood ratio.
• Albumin
• Dextran
• Hetastarch
• Gelatin
Technique:
• Draw blood either
• Under anesthesia
• Prior to induction
• Blood withdrawal rate must parallel the
administration of appropriate diluent
volumes to assure normovolaemic and
circulatory stability.
• Serial HCT
• Collections in bags & bottles
• Monitoring
Methods:
• Ferraric Method:
• Preoperatively collect:
• 1 - 3 U of RBC suspended in saline
together with an average of 1.6 x 10
platelets & 460 ml of plasma collected
preoperatively.
Takaonʼs Method:
• If Blood loss > 400 ml, 500 ml of RL is
given, after which 600 ml of blood is
withdrawn, which is replaced by 600 ml of
dextran 70.
• If Blood loss > 1L 600 ml of blood is taken
& is replaced with equal volumes of 600
ml dextran 70.
40

14. Replacement therapy for coagulation factor deficiency Dr Azam’s Notes in Anesthesiology 2013
Factor Therapeutic dose Component / derivatives

i) Fibrinogen 1 units / 5kg body wt Cryoprecipitate(100-250gms fibrinogen/bag)
ii) Prothrombin 10-20ml plasma /kg Plasma or prothrombin complex concentrate
iii) Factor V 20ml fresh frozen plasma/kg Fresh frozen plasma
iv) Factor VII 10-20ml plasma/kg Plasma or prothrombin complex concentrate

v) Factor VIII 15-50 units/kg Cryoprecipitate (100 units/bag) factor VIII concentrate
vi) Factors IX 20-80 units/kg Prothrombin complex concentrate plasma (1 unit of

factor IX/ml)
vii) Factor X 10-20ml plasma/kg Plasma or prothrombin complex
viii) Factor XI 10-20ml plasma/kg Plasma
x) Factor XIII 4-6 bags Cryoprecipitate or 500ml plasma Plasma or Cryoprecipitate
41

15. Partial thromboplastin time - PTT Dr Azam’s Notes in Anesthesiology 2013
Partial thromboplastin time:

• PTT measures the intrinsic pathway i.e. factor Administration of heparin:
I,II,V,VIII,IX,X,XI,XII. 1. Heparin can be given subcutaneously / IV.
• Specimen: citrate anticoagulated whole blood to be kept 2. IV can be intermittent or continuous infusion.
refrigerated and transported as soon as possible. 3. Usually in dose of 400-500 units / kg / day divided into 6th hrly
• Procedure: Performed with addition of contact activator (celite, dosage.
kaolin, micro silicate, ellagic acid). 4. 3 levels of heparin therapy.
• Plasma sample is added to activator and incubated at 370C for 5 5. Low dose (10,000 – 20,000 units/day) mainly used as prophylaxis
minutes. Thromboplastin preparation is added, mixed with against venous thrombosis (DVT), measurable changes in APTT
addition CaCl2 and the timer is started. usually does not occurs.
6. Moderate dose (20,000 to 60,000 units/day) used in patient
Normal range: 25-‐39 seconds without active thrombo embolic disease.
• Healthy premature babies have prolonged PT, PTT, TT which 7. APTT is adjusted to 1½ to 2 times the control.
returns to normal at 6 months. 8. High dose (60,000 to 1,00,000 units / day) used in patient with
• Panic range:> 70 seconds active thrombo embolic disease.
Use: 9. This high dose is usually used for first 24-48 hrs and then
• Evaluation of intrinsic pathway, Heparin therapy, Screening for reversed back to a dose of 30,000-45,000 units/day.
hemophilia A and B (factor VIII) , dysfibrinogenemias, DIC, -
liver failure, Vitamin K deficiency
Contraindications:
• Specimen obtained less than 3 hrs after heparin doses.
• About 30% of normal concentration of factor V, VIII, IX, X, XI and
XII will maintain a rate of thrombin formation sufficient to
produce normal PTT. Prolongation occurs when any of the
above single clotting factor falls below this level.
• Heparin à active serine protease
Control of heparin therapy
• Heparin is an acid mucopolysaccharides found in Mast cells and
Basophils, which inhibits all the active serine proteases like IIa,
IXa, Xa, XIa and XIIa.
• Response to heparin can be measured by whole blood PTT,
APTT whole blood clotting time and PTT with comparable
responses.
42

16. Activated Clotting Time - ACT Dr Azam’s Notes in Anesthesiology 2013
Synonymous à Activated clotting time ground gloss clotting Uses:

time is a screening time for coagulation deficiencies and is • Monitoring of heparin therapy.
of special application to the monitoring of heparin effect. • A baseline value of ACT is determined
Specimen: Fresh whole blood that is free of venepuncture - Before IV administration of heparin
derived thromboplastin. - Approximately 3 mins after administration
Procedure: manually mixing of whole blood with an - 30 mins intervals thereafter.
activator substance such as celite / kaolin. • Use to monitor anticoagulation when large doses of heparin are
• Contact of the activator with the blood initiates the used as during cordial surgical procedure.
activation of the clotting cascade. • During CPB the anticoagulant effect of heparin is often is
• Commercially available timing systems are uses clinically considered as adequate if the ACT is more than 300 seconds,
to measure the activated clotting time. These devices questionable with ACT between 300-180 sec and inadequate with
detect the onset of clot formation. ACT < 180 sec.
• Tubes of freshly drawn blood are incubated at 370C and • In patients receiving antifibrinolytic agent aprotinin, kaolin should be
tilted at 300 second intervals until the flow of blood stops. used to measure ACT, because it will bind the aprotinin and remove
• Tilting and recording can be made manually or by it from the plasma.
automated machines.
Normal range à 9-120 seconds (Millerʼs text 107± 13 During CPB:
seconds) • ACT = 300 - Adequate
Limitations à Relatively insensitive to lower • ACT = 300 - 1800 Questionable
concentration of heparin • ACT = < 180 in adequate.
• Insensitive to factor VII deficiency
• Hypothermia and haemodilution à prolongs ACT
• It assays over all coagulation activity and during
monitoring for heparin therapy, prolonged values may not
be exclusively due to heparin therapy.
• Abnormal values due to platelet abnormality.
43

17. Prothrombin Time - PT Dr Azam’s Notes in Anesthesiology 2013
• P T, measures the extrinsic pathway (I, II, V, VII, X) of INR (INTERNATIONAL NORMALIZED RATIO)
coagulation and common pathway. • The INR was established as a mean of standardizing the PT for oral
Specimen à sodium Citrated anticoagulated whole blood. anticoagulant therapy.
Procedure à clotting time of Citrated anticoagulated plasma Calculated as INR = PT of patient (sec)
is determined after the addition of optimum concentration of
calcium and an excess of thromboplastin. Clot detection is Mean of normal PT(ISI)
either normal or by an automated device.
• The final result depends on the concentration and source of
• INR rate is used in monitoring patient in oral anticoagulant therapy
thromboplastin, calcium concentration and the method used
and it is recommended to monitor. INR of 1.3-1.5 (15-18 seconds) but
to detect clot formation. Therefore results may vary a great
slightly higher range of 1.5-2.0 is recommended for patients with
deal from laboratory to laboratory.
prosthetic valves and recurrent embolism.
• Normal range – 10-14 seconds.
•
• Premature, new born have normally prolonged PT, TT,
APTT which comes to normal range by 6 months. • INR of 1.5 to 2.0 in prosthetic valve and recurrent embolism.
• Panic range à> 20 secs à non anticoagulated
• 3 times control à anticoagulated
Use:
• Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, afibrinogenemia, liver failure, DIC,
heparin effects, coumarin / warfarin effects, screening of
vitamin K deficiency, and factor V, VII, & X (5, 7, 10)
• Prolongation of the PT usually reflects severe liver
decrease unless vitamin K deficiency is present because
only 20-30% of normal factor activity is required.
• Failure of the PT to correct, following parenteral
administration of vitamin K implies severe liver disease,
correction normally requires 24 hrs.
• Limitations – PT drawn less than 2 hrs after heparin
administration is prolonged( minimum duration is more than
6 hrs).
44

18. Describe the coagulation factors. How do you investigate a case of intra Dr Azam’s Notes in Anesthesiology 2013
operative coagulopathy?
• Coagulation, often referred to as secondary hemostasis Primary hemostasis: Platelet plug formation
involves formation of a fibrin clot, which usually binds and
strengthens a platelet plug. 3 stages
• Fibrin can be formed via one of the 2 pathways that involve 1. Adhesion – circulating platelets adhere to subendothelial collagen via
activation of soluble coagulation precursor proteins in blood. specific glycoprotein receptor. Stabilized by circulating glycoprotein
Coagulation factors: called vWf which forms additional bridges via GPIb.
I! Fibrinogen 2. Release of platelet granules: collagen (as well as epinephrine and
II! Prothrombin thrombin) activates platelet membrane bound
III! Tissue thromboplastin
IV ! Calcium/Labile Factor
V! Proaccelerin ! 4="6>="3'>%60)-))
VII! Proconvertin ?)
VIII! Antihemophilic factor !) !) )
IX! Christmas factor !"#$%&'"()"*)+,-.) /01#%(23%&'"())
X! Straut power factor ) )
!) !)
XI! Plasma thromboplastin antecedents (PTA -/48)+,-.8)!%7&"#)98)9:!8)!';#'("10()
4"&0(&)5%6"7"(6&#'7&"#))
XII! Hageman factor ) )
%(<)!';#"(07&'()))
XIII! Fibrin stabilizing factor (Laki-Lorand factor)
Factors contributing to excessive bleeding during and following 3. Aggregation: These factors attract and activate additional
surgery: platelets – resulting in platelet plug.
• Hemostasis following trauma and surgery is dependent on 3 4. Coagulation cascade: Fibrin can be formed via one of the 2
major processes. A defect in any of the following leads to pathways.
bleeding diathesis and increased blood loss. • The extrinsic pathway – triggered by the release of tissue
lipoprotein (thromboplastin) from injured cells.
Seconds:
• More important pathway in humans.
1. Vascular spasm • Factors involved – 1, 2, 5, 7 and 10.
2. Formation of platelet plug – primary hemostasis • Test prothrombin time.
Minutes:
• Coagulation of blood – secondary hemostasis
• Vascular spasm: result of release of humoral factors and local
myogenic reflexes.
• Sympathetic mediated vasoconstriction in medium – sized
vessels.
45

Describe the coagulation factors. How do you investigate a case of intra operative Dr Azam’s Notes in Anesthesiology 2013
coagulopathy?Continuation:
Intrinsic pathway:
• Triggered by interaction between sub-endothelial collagen with circulating factor XII,
HMWK and prekallikrein.
• Factors involved – 1, 2, 5, 8, 9, 10, 11,12,
• Test – PTT
• Regardless of pathway activated, the coagulation cascade is ends in the conversion
of fibrinogen to fibrin.
• Thrombin plays a central role in coagulation.
• Thrombin then converts fibrinogen to soluble fibrin monomers that polymerize on
the platelet plug.
Tests for coagulation:

Test Normal value Measured
1) Bleeding time 3-10 minutes Platelet function vascular integrity
2) Platelet count 150,000 to 400,000 cells/
mm3
3) Prothrombin time 10-12 seconds Factors 1, 2, 5, 7, 10
4) PTT 25-35 secs Factors 1, 2, 5, 7, 9,10, 11,12
5) Activated clotting time 90-120 secs same as above
6) Thrombin time 9 -11 seconds Factors 1, 2
7) Fibrinogen 150-250 mg/dl
8) Fibrin degradation < 4 mg/ml
product
46

19. Categorization of coagulation disorders: Dr Azam’s Notes in Anesthesiology 2013
! !"#"$%&'#(! )*+,%#"$-!
!"#$%&'(')*+*),-*.* ./0!
/$,*0'(("12),-*-'3")3"* 1"#%23"#'&%4"-'5&%*2'6,7'&%25!
/5&#'-23"#'&%4"-*2'6,7'&%25-!
+4'12$,$5',"#')**
;'(<8'$,)(*8&2$#1$7=8"*
-
6)78$2*/*-"4**
%",8)**
6)78$2*/999*-"4*
- ;'(<8'$,*$4*%2$7$)5<(),83*
:2$8"',"*-"4*
- >)33'?"*1($$-*82),34<3'$,**
+,8'8&2$#1',*999*-"4*
- @=%"*$4*3<25"2=*
AB:.C*.2)',*82)<#)C*
$28&$%"-'7C*$138"82'7D*
;2<5*',-<7"-*&"#$22&)5"*
;2<5*',-<7"-*%()8"("8*-=34<,78'$,**
9@:*
@@:*
B)8&"8"2E',-<7"-*8&2$#1$3'3*
?'8)#',*F*-"4G**
• FFP – 1 u/ml of factor VIII

• Cryoprecipitate– 5 -10 u/ml factor VIII
• Factor VIII concentration – 40 u/ml factor VIII
• DDAV - ↑ 2 to 3 times.
47

20. Describe various test used for monitoring peri-operative coagulation.
Traditionally, perioperative coagulation monitoring has focused on:
(1) preoperative testing to identify patients at increased risk for perioperative bleeding
(2) intraoperative monitoring of heparin therapy during cardiac and vascular surgery.
Test for Monitoring Perioperative Coagulation.
Partial thromboplastin time:

• PTT measures the intrinsic pathway i.e. factor PROTHROMBIN TIME: INR (INTERNATIONAL NORMALIZED
I,II,V,VIII,IX,X,XI,XII. • P T, measures the extrinsic pathway (I, II, V, VII, X) of RATIO):
coagulation and common pathway. • The INR was established as a
• Normal range: 25-39 seconds mean of standardizing the PT for
• Normal range – 10-14 seconds.
• Healthy premature babies have prolonged PT, oral anticoagulant therapy.
• Premature, new born have normally prolonged PT, TT,
PTT, TT which returns to normal at 6 months. • Calculated as INR = PT of patient
APTT which comes to normal range by 6 months.
• Panic range:> 70 seconds (sec)/ Mean of normal range
• Panic range à> 20 sec à non anticoagulated
• Use: • INR rate is used in monitoring
• 3 times control à anticoagulated
• Evaluation of intrinsic pathway, Heparin therapy, Use: patient in oral anticoagulant
Screening for hemophilia A and B (factor VIII) , therapy and it is recommended to
• Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, DIC, - liver failure, Vitamin K dysfibrinogenemias, afibrinogenemia, liver failure, DIC, monitor. INR of 1.3-1.5 (15-18
deficiency heparin effects, coumarin / warfarin effects, screening seconds) but slightly higher range
• Control of heparin therapy of vitamin K deficiency, and factor V< VII, & X (5, 7, of 1.5-2.0 is recommended for
• Heparin is an acid mucopolysaccharides found in 10) patients with prosthetic valves and
Mast cells and Basophils, which inhibits all the • Prolongation of the PT usually reflects severe liver recurrent embolism.
active serine proteases like IIa, IXa, Xa, Xia and decrease unless vitamin K deficiency is present •
XIIa. because only 20-30% of normal factor activity is • INR of 1.5 to 2.0 in prosthetic valve
• Response to heparin can be measured by whole required. and recurrent embolism.
blood PTT, APTT whole blood clotting time and • Failure of the PT to correct, following parenteral
PTT with comparable responses. administration of vitamin K implies severe liver
disease, correction normally requires 24 hrs.
• Limitations – PT drawn less than 2 hrs after heparin
administration is prolonged( minimum duration is more
than 6 hrs).
48

Describe various test used for monitoring peri-operative coagulation.Continuation:
Test for Monitoring Perioperative Coagulation.
ACTIVATED COAGULATION TIME (ACT): THROMBOELASTOGRAPHY:

• Activated clotting time ground gloss clotting time is a
screening time for coagulation deficiencies and is of • It is a viscous elastic technique which
measures entire spectrum of clot formation
special application to the monitoring of heparin effect. from early fibrin strands to clot retraction and
• Normal range à 9-120 seconds (Millerʼs text 107± eventual fibrinolysis. This test evaluate clot
13 seconds) formation as a dynamic process unlike
Uses: standard coagulation tests which measure
• Monitoring of heparin therapy. isolated endpoints.
• A baseline value of ACT is determined
i. Before IV administration of heparin
ii. Approximately 3 mins after administration
Uses:
iii. 30 mins intervals thereafter.
• Coagulation monitoring during
• Use to monitor anticoagulation when large doses of
heparin are used as during cordial surgical procedure. • Liver transplantation
• Obstetric anesthesia
• During CPB the anticoagulant effect of heparin is
often is considered as adequate if the ACT is more • Trauma anesthesia (massive
than 300 seconds, questionable with ACT between transfusion)
300-180 sec and inadequate with ACT < 180 sec. • Diagnosis pre-coagulant defect.
In patients receiving antifibrinolytics agent aprotinin, - Platelet dysfunction
kaolin should be used to measure ACT, because it will - Fibrinolysis
bind the aprotinin and remove it from the plasma. - Hyper-coagulation state
R—Reaction time for initial fibrin formation • Real time detection of clotting
! N à 6-8 mins abnormalities in liver
! ↑ in deficiency of a coagulation factors. transplantation CPB
R + K à coagulation time • Differentiates surgical bleeding
! ! N à 10-12 mins. from coagulopathy in cardiac
α0à clot formation rate surgery.
! N à> 500↓ in coagulation disorder.
MA à Maximum Amplitude
A60à Amplitude 60 min other MA
F à Whole blood clot lysis time 49
! N à> 300 min
Describe various test used for monitoring peri-operative coagulation.Continuation:
THROMBOELASTOGRAPHY: Continuation:
Normal Hemophilic Thrombocytopenia Fibrinolysis Hypercoagulability

1) Prolonged R 1) Prolonged R 1) ↓ MA 1) Shortened R
2) ↓α0 2) ↓α0 2) ↓α0 2) ↑ MA
3) ↓ MA 3) ↓ MA 3) ↓ F 4) Prolonged F
Treatment for the TEG:

TEG Parameters Treatment
R 11 - 14 min 2 x FFP or 10 ml/kg
R > 14 min 4 x FFP or 20 ml/kg
MA 46 - 50 mm 1 Platelet concentrates
MA < 46 mm 2 platelet concentrates
Angle < 52° 2 x FFP or cryoprecipitate
Ly 30 > 8% Antifibrinolytics
50

21. Thromboelastography Dr Azam’s Notes in Anesthesiology 2013
Definition:
• It is a viscous elastic technique which measures entire spectrum of R—Reaction time for initial fibrin formation
clot formation from early fibrin strands to clot retraction and eventual ! N à 6-8 mins
fibrinolysis. This test evaluate clot formation as a dynamic process ! ↑ in deficiency of a coagulation factors.
unlike standard coagulation tests which measure isolated endpoints. R + K à coagulation time
Method of recording: ! ! N à 10-12 mins.
• 0.35 ml of blood placed in a disposable curette within the instrument. α0à clot formation rate
The curette continuously rotates around an axis of 50. ! N à> 500↓ in coagulation disorder.
• A metal piston attached by a tissue wire to an electronic needle MA à Maximum Amplitude
recorder is lowered into the blood in the curette. A clot formation A60à Amplitude 60 min other MA
occurs, the piston become with in the clot & the solution of curette is F à Whole blood clot lysis time
then transfused to piston and to the electronic recorder. ! N à> 300 min
• Hyper coagulated within 30 min of obtaining the sample.
Uses:
• Coagulation monitoring during
• Liver transplantation
• Obstetric anesthesia
• Trauma anesthesia (massive transfusion)
Uses:
Diagnosis pre-coagulant defect.
- Platelet dysfunction
- Fibrinolysis
- Hyper-coagulation state
Real time detection of clotting abnormalities in liver
transplantation CPB
Differentiates surgical bleeding from coagulopathy in cardiac
surgery.
• It aids in the diagnosis of a procoagulation deficiency (hemophilia), Disadvantages:
platelet dysfunction, fibrinolysis, DIC.
Lack of specificity associated with abnormal findings
Qualitative assessment is not possible
Schematic depiction of coagulopathy as selected by the
Thromboelastography compared with normal one
51

Thromboelastography Dr Azam’s Notes in Anesthesiology 2013
Normal Hemophilic Thrombocytopenia Fibrinolysis Hypercoagulability

1) Prolonged R 1) Prolonged R 1) ↓ MA 1) Shortened R
2) ↓α0 2) ↓α 0 2) ↓α0 2) ↑ MA
3) ↓ MA 3) ↓ MA 3) ↓ F 4) Prolonged F
• R - Reaction time fibrin formation

• K - Time & Kinetics for fibrin cross linkage. Treatment for the TEG:
• α (Alpha) - Strength of the clot & clot formation
ratio. TEG Parameters Treatment
• MA - Maximum Amplitude for fibrin & platelet
interaction. R 11 - 14 min 2 x FFP or 10 ml/kg
• Ly 30 - Measures lysis time after MA. R > 14 min 4 x FFP or 20 ml/kg
MA 46 - 50 mm 1 Platelet concentrates
MA < 46 mm 2 platelet concentrates
Angle < 52° 2 x FFP or cryoprecipitate

52
Ly 30 > 8% Antifibrinolytics
22. Assessment of blood Loss during Surgery Dr Azam’s Notes in Anesthesiology 2013
Measurement of blood loss:

• Normal blood volume in an adult is 70ml/kg
for 17.7% of body weight. Total blood 1) Visual observation of degree of bleeding
volume can be measured as the sum of the 2) Clinical signs: give indirect information concerning blood loss. These include fall
red cell volume and plasma volume or from in B.P., fall in C.V.P., tachycardia, sweating and pallor of skin. It is advantageous to
formulae depending on height and weight. replace blood loss before these signs become evident.
These methods give a reasonable estimate in the case of minimal blood loss.
• One of the most important tasks of
anesthesiologist is to continuously monitor Errors are likely to be cumulative if blood loss continues over a prolonged period.
and estimates blood loss. Unless estimates 3) Gravimetric method – simplest, most common employed blood loss estimate by
are complicated by occult bleeding into measurements of gain in weight of swabs and towels, together with measurement
wound or under surgical drapes, accuracy of contents of suction bottle. 1ml of blood weighs 1g.
is importance to guide fluid therapy Weighing of swabs underestimates blood loss by 25%.
transfusion. 4) Dilutional methods:!
a) colorimetric method
• Most commonly used method for b) use of radioactive tracer
estimating blood loss is measurement of
a. Calorimetric method – swab + towel mixed thoroughly with large known volume
blood in surgical container and visually
of fluid which is then estimate calorimetrically. Error may occur due to
estimating blood on surgical sponges and
incomplete extraction or contamination with bile. patient hemoglobin must be
laparotomy pads.
known.
• A fully soaked sponge (4x4) said to hold 10 Blood loss = Calorimeter reading X Volume of Solution/200 X % of Pt Hb
ml of blood; where as soaked lap holds In operations involving complex exchanges of blood (extracorporeal circulation). It
100-150 ml. may be useful to weigh whole patient before and after operation.
• More accurate estimates are obtained if
sponges and laps are weighed before & b) Use of radioactive tracer dilution methods:
after use. When measuring the volume of anybody compartment by this method, it is
important that the tracer used remain within that compartment.
• Serial hematocrit / hemoglobin
concentration reflect ratio of blood loss to In the case of blood volume, either the patientʼs own red blood cells (labelled with
plasma, not necessarily blood loss. Cr51 following incubation with the isotope or pooled human albumin (labelled with
Hematocrits may be useful during long I125 or I131) are used. All 3 isotopes are gamma emitters, but I125 is the isotope of
procedure or when estimates are difficult. choice because it emits less energy. The activity of the tracer is first measured and
then injected intravenously.
53

Assessment of blood Loss during Surgery Dr Azam’s Notes in Anesthesiology 2013
• The activity remaining in the empty syringe is measured and Exact point is based on patientʼs medical condition & surgical
deducted from the amount of the isotope injected. After 10-15 procedure.
minutes, a sample of blood is withdrawn from the opposite arm. 1. Estimate blood volume.
This is to ensure there is no contamination of the sample from any 2. Estimate RBC volume at pre operative hematocrit.
isotope remaining at the injection site. The activity of this sample is 3. Estimate RBC volume at hematocrit 30% assuming
then measured and the dilution volume calculated from the result. normal blood volume is maintained.
Repeated measurements can be made to estimate the change in 4. Calculate red cell volume lost when Hematocrit is 30%.
blood volume with allowance made for residual radio activity from 5. RBC volume lost =RBC preoperative – RBC volume 30%.
the previous measurements. 6. Allowable blood loss = RBC volume (lost) x 3
• In a shocked patient, the time taken for mixing throughout the total
blood volume may be in excess of the 10-15 minutes usually Hemorrhagic Shock:
allowed. So the measurement is a better indication of the effective Class I Class II Class III Class IV
circulating volume than it is of the total blood volume errors may
Blood loss 750 750-1500 1500-2000 ≥ 2000
also arise from loss of the injected isotope by vigorous hemorrhage
before mixing is complete. % or volume 15% 15-30% 30-40% ≥40%
Average blood volume. Pulse rate < 100 > 100 > 120 ≥ 140
Neonates: Premature 95 ml/kg, Full term 85 ml/kg, Infants 80 ml/kg BP Normal Normal Decreased Decreased
Adults: Men 75 ml/kg Women 65 ml/kg Pulse Normal / Decrease Decrease Decrease
Replacing blood loss: increase
pressure
• Ideally blood loss should replace with crystalloid or colloid to Capillary Normal Positive Positive Positive
maintain intravascular volume (normovolemia) until danger of
refilling (3 -4
anemia outweighs risks of transfusion.
seconds)
• At that point further blood loss is replaced with transfusion of RBCs
Respiration 14-20 20-30 30-40 > 35
to maintain Hb concentration or hematocrit at that level for most
rates
patients it corresponds to Hb between 7-8 g/dl.
Urine output ≥30 20-30 5-15 Negligible
• Hb < 7gm/ dl à cardiac output ↑ to maintain O2 delivery.
( ml)
• Hb – 10gm/dl à for patients with cardiac / pulmonary disease / CNS mental slightly anxious Mild anxious Anxious Confused&
elderly.
status &confused lethargic
Replace:
Fluid Crystalloid Crystalloid Crystalloid & Crystalloid &
• 1 ml of Blood = 3 ml crystalloid
replacement blood blood
• 1 ml of Blood = 1 ml colloid
• Patients with normal hematocrit should generally be transfused
only after losses greater than 10-20% of their blood volume.
54

23. Sickle Cell Anemia & Anesthesia Dr Azam’s Notes in Anesthesiology 2013
• Sickle cell anemia was first noted clinically by Pathophysiology:

J.B. Herrick in 1904. in 1927 Hah and Gellespie Low PaO2
↓
induced hypoxia and acidotic sickling and Deoxygenation of Hb-S
incriminated haemoglobin as the cause, by ↓
demonstrating them in ghost erythrocyte Sickle shaped RBC
• Sickle cell disease is a hereditary ↓
hemoglobinopathy in which the red cells contain Sickled Hb-S has 2 reactive sites
Hb-S instead of Hb-A. Hb-S differs from normal ↓
Hb-S molecules bind with each other
adult Hb-A by the substitution of valine for
↓
glutamic acid at β-6 of Hb molecule. Long aggregates / tactoids (rigid, less soluble)
Types - Two Types ↓
• Sickle cell trait (heterozygous) Increased viscosity of blood
• Sickle cell anemia (homozygous) ↓
• Sickle cell trait – asymptomatic carrier state for Stasis of blood flow
Hb-S ↓
Localized / generalized vascular occlusion
• Incidence in American blacks – 8-10% ↓
• RBC have Hb-S concentration < 50% Infarction crisis
[38-45%] Vaso-occlusion common in liver and kidney where portal circulation PO2 is usually
• Sickle cell anemia – incidence in American low.
blacks – 0.2% Aplastic crisis – Characterized by bone marrow depression – cessation of
• RBC have Hb-S concentration 70-98% erythropoesis
↓
• Characterized by Rapidly declining hematocrit Often associated with viral infection
– Chronic hemolysis Sequestration crisis –Is due to depletion of circulating RBC by virtue of
– Acute episodic vaso-occlusive crisis pooling of these cells in liver and spleen. Mainly affects children and infants –
• Sickle cell crisis–Life threatening complication may need immediate transfusion.
in contrast to anemia Diagnosis -
1) Hb – 6-9g/dl
• Peripheral smear – normocytic normochromic anemia
2) Sickle test – Precipitation reaction
3) Sickle test
4) Haemoglobin electrophoresis – definitive test
55

Sickle Cell Anemia & Anesthesia. Continuation: Dr Azam’s Notes in Anesthesiology 2013
Treatment: Clinical manifestations:

Principles of Treatment of sickle cell crisis 1. Those due to infarctive events due to occlusion of
• To keep the patient warm blood vessels with sickle cells.
• To alleviate pain 2. Those due to chronic hemolytic anemia (Hb 6-8 gm/dl).
• To rehydrate Infarctive events are responsible for wide spread organ
• To treat infection, hypoxia, acidosis damage.
• Pain – Treatment with an opioid Cardiovascular system: Cor-pulmonale due to repeated
• The use of epidural analgesia using local anesthetic / opioid may be pulmonary emboli, and also, secondary to high output failure.
useful if pain is in lower extremities. Central nervous system: Cerebrovascular accidents are
• Partial exchange transfusion – with fresh normal RBC Containing Hb-A- common especially in children. Stroke is significantly reduced
leads to decreased HbS concentration by transfusion programme of 2 units every fortnight. Stroke
Goals: may be induced by hyperventilation, severe anemia, infection,
• To ↑ HbA conc. To close to 50% sickle cell crisis.
• To keep hematocrit below 35% Respiratory system: Total Lung Capacity (TLC) and vital
• Oral bicarbonate (up to 20 g/day) to produce mild Alkalization capacity (VC) are frequently decreased. Pulmonary embolism
and respiratory infection are common in post operative period.
Management of anesthesia Genitourinary system: Renal abnormalities are established by
• Pt with sickle cell trait – Not at increased risk during perioperative period the age of five to either years. The hypertonic medulla
• Pt with sickle cell anemia – Increased risk concentrates Hb and with its low oxygen partial pressure
• Orthopedic conditions are frequent in these patients. promotes sickling. This produce papillary necrosis, hematuria
• Ex. Necrosis of head of femur, Leg ulcers, Gall stones, Priapism and inability to concentrate urine and renal failure. Priapism is
a common occurrence.
FACTORS CAUSING SICKLING
Hepatic and splenic infracts: May be focal or diffuse. Sever
1) Low PO2 liver dysfunction can result in pseudo-cholinesterase
! In sickle cell anemia PaO2< 40 mm Hg deficiency.
! In sickle cell trait PaO2< 20 mm Hg Skeletal system: Aseptic necrosis of femoral head and
2) pH salmonella infection of small bones of the hand.
! Decreased pH – Acidosis – Favors sickling
! Sickling – greater in veins than in arteries
3) Decreased body temperature
Exposure to cold – Vasoconstriction
↓
Stasis of blood Clow
↓
Sickling
4)Dehydration – increases viscosity – stasis – sickling 56

Goals of preoperative RBC transfusion

Chronic hemolysis of erythrocytes is reflected by:
1. To increase HbA conc. Close to 50%
1. Elevated levels of plasma bilirubin leading to cholelithiasis and 2. To achieve hematocrit of 35%
cholecystitis.
2. Periodic transfusion increases risk of viral hepatitis. Premedication:
3. Hemochromatosis ensues with iron overload following repeated • Avoid drugs that causes respiratory depression.
transfusions. It leads to cirrhosis of liver and left ventricular • Pre-oxygenate well; induction with thiopentone sodium and
dysfunction also. succinylcholine followed by tracheal intubation and
4. White cell function is depressed with increased susceptibility to controlled moderate hyperventilation with nitrous oxide and
infection. oxygen. 30% oxygen is adequate and judicious doses of
halothane to promote vasodilatation
Infarctive crisis:
! This is triggered off by infection, trauma or associated Intraoperative management
elevations in temperature. It is characterized by acute onset of pain • Avoidance of acidosis due to hypoventilation
usually abdominal with fever and vomiting. • Maintenance of optimal oxygenation
Treatment: • Prevention of circulatory stasis due to
! - Improper body positioning
1. Adequate hydration. ! - Use of tourniquets
2. Partial alkalization of blood • Maintenance of normal body temperature
3. Partial exchange transfusion with erythrocyte containing • Pre-oxygenate with high inspired O2 tension
haemoglobin A. • Because to maintain normal to increased PaO2
4. Antibiotics.
In infants – splenomegaly children (6 yrs) – autosplenectomy. Regional anesthesia preferred to G.A.
• Administration of supplemental O2
Pre operative assessment and preparation:
• Epidural / spinal – Produce compensatory vasoconstriction
1. Existing organ dysfunction should be assessed. and decreased PaO2 in non blocked areas – sites of
2. Aggressive pre-operative hydration is essential. infraction. There may be decrease in number of circulatory
3. Prophylactic antibiotic cover. sickle cells during and immediately after G.A.
4. Systemic preoperative alkalization which on one hand confers
an anti-sickling effect and on the other hand shifts the oxy- Prevention of circulatory status requires.
Haemoglobin curve to left. - Maintenance of cardiovascular stability by adjustment
Correction of co-existing infection. of depth of anesthesia.
Preoperative transfusion – Depend on severity of anemia and - Anticipation and Rapid correction of hypotension.
magnitude of planned surgery - Maintenance of I.V. fluid volume by crystalloids
57

Post operative management: Post operative period:

• Continue oxygenation up to 8 hrs.
• Early mobilization of patient.
• Chest physiotherapy.
• Adequate antibiotic cover to control chest infection.
• Careful watch for infarction crisis; bone pain usually heralds bone
infarcts. Heparin and Magnesium Sulfate should be given immediately.
• Maintenance of intravascular volume.
58

24. Anemia & Anesthesia. Dr Azam’s Notes in Anesthesiology 2013
! ! ! Pathophysiological Classification
Definition:
!
Anemia is a condition in which there, is
decreased oxygen carrying capacity of the
blood, because of reduced concentration of !"#$%&&'#%&((## !!"#!34520-'#6$.#40&'+*,2&1## !!!"#;<*-((2=-##6$.#'-(,0+*,2&1##
haemoglobin in the presence of a normal or )"#)*+,-## )"#7+,02,2&15%## !" !"#$%"&%'()*+*'#&(%"(,-.##
near normal blood volume for the age and sex !"#$%&'()'$$ '5$6&21$7+8./.+1/9$$ '5$A<?$)+):&'1+$7+8+/-@#$$
of the individual. It is not a primary disease but $"#./0&12*## :5$;.-').1$<=>$'17$820./$'/.7$ !"F$G#$H,3+&2/9-2@.@$$
a manifestation of some other underlying !"#$*+,-./$(0/+&$ 7+8./.+1/9$$ $ G#$!00.,-2/9-2@.@$$
disease. )+12&&3'4.'$$ /5$*&2-+.1$+1+&49$)'01(-&.-.21$$$ :5$A<?$+1I9)+$7+8./.+1/9$$
<5$8-40-((2&1#&9#-0:,/0&4&-2(2($$ !"F$JK*L$7+8./.+1/9$$
Normal haemoglobin levels: '5$?3&21./$7.@2&7+&@$$ /5$L.@2&7+&$28$G:$@91-3+@.@$$
• Men = 13 – 18 g/dl !"#$618+/-.21$$ !"F$H./E0+$/+00$'1+).'$-3'0'@@'+).'$$
• Women = 11.5 – 16.5 g/dl - %#<$ <#$;<,021(2*#-99-*,#&1#6$.$
• Full term infant = 13.5 – 19.5 g/dl - ?#2@-+2)9+0--.@$$ '5$B1-.:279$)+7.'-+7$$
• Children = 11-14 g/dl A3+()'-2.7$'&-3&.-.@$$ !"#$%&'1@8(@.21$&+'/-.21$$
• In India, usually Hb concentration of less :5$?3&21./$&+1'0$8'.0(&+$$ B(-2'1-.:27.+@$!$HD!M$L&(4@$
than 10 g/dl is taken is anemia. /5$B,0'@-./$'1+).'$$ :5$618+/-.21$!$C'0'&.'$$
75$C'0.41'1/.+@$ /5$?3+)./'0$N$0+'7$,2.@21.14$$
Etiology and classification of anemia:
Classification: !"#$D+(E+).'$$
• Pathophysiological C9+02)'$$
• Etiological $
! ! ! Morphological classification
!
!"#$"%&'(%)*"#$"%+#"$(%)) ,-./0.12-.)) ,5%#"%&'(%)5*6$(5))

!"#$%&''($&'))$$ 3140.3/0,-.)) !"#$?+@3&'>&3)./0$37+,/3$$$
- *+,'&-./0$$ !":$;6'7$(+8/0/+70-$37+,/3$$
- 12&3)./0$$ - <53&3))3+,/3$$
- 456'7/0$6+73&$83/&96+$$ - =/(+6'>&3)./0$37+,/3$$
- 17+,/3$'6$056'7/0$
/78+0./'7$$$
59

Anemia & Anesthesia.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Compensatory mechanisms in anemia: Clinical features of anemia

I. Increased blood flow to the tissues (Decreased Viscosity, increased Mild Moderate Severe
Cardiac output & redistribution of tissue blood Flow):
Asymptomatic Dyspnoea on exertion Dyspnoea at rest
Tiredness Palpitations Angina pectoris in older
Decreased blood viscosity
Weakness Giddiness patients
↓
Easy fatigability Tinnitus ! murmurs
Fall in peripheral vascular resistance
Lassitude Spots before eye Cardiomegaly
↓ anorexia Congestive cardiac
Increased blood flow in microcirculation Lack of concentration Failure
↓ JVP
Increased venous return Edema
↓ High output state
Increased cardiac output (Collapsing pulse)
clouding of conscious
II. O2 transport capacity is 100% at hematocrit of 40% but physiological koilonychias
supply of O2 to tissues is optimum at hematocrit of 30%
III. Redistribution of tissue blood flow in metabolically active tissue à
+Brought about by
1. Auto-regulation 1. Haemoglobin à decreased
2. By input from autonomic nervous system 2. RBC count à decreased (N à 4.5 – 5.5 million / mm)
3. Increased cardiac output 3. Total WBC count à increased if infection
4. Increased tissue oxygen extraction 4. Differential count
5. Peripheral smear:
Effect of anemia on myocardial O2 consumption: I.D.A Megaloblastic Aplastic
At a Hematocrit of 20-25%.
↓ Microcytic Macrocytic RBC Normocytic
Tachycardia and increased contractility hypochromic Hypersegmented Normochromic
Anisocytosis Neutrophils Leucopenia
↓
Poikilocytosis Thrombocytopenia
• Increased cardiovascular work and increased O2 demand by the heart:
• Heart: ↑ O2 extraction normal 65-70% in heart,↑ coronary blood flow
• In anemia O2 extraction quickly reaches maximum. C.O doubled (2
times),CBF trebled (3 times)
• In healthy persons – if Hb decreases by 50%
60

VI) Anesthetic management:

6. Red cell indices: Preoperative evaluation:
• MCV = PCV/RBC Count 1) To search for cause and correction of anemia
• Normal 75 to 100 femtoliters (fl) 2) To assess the nature and degree of compensation/
• ↑megaloblastic 3) To evaluate the amount of reserve available for intraoperative
• ↓ in IDA compensation.
• MCH = total Hb/RBC count • History à weakness / dyspnoea / palpitation / chronic blood loss / jaundice /
• Normal 24 – 33 pg parasthesia / smoking / pain abdomen.
• ↓IDA • Examination à Build, nourishment, pallor, icterus, GPE oedema, clubbing,
lymphadenopathy.
• MCHC = Total Hb/PCV • Pulse, B.P. UVP, Shift of apex beat.
• Normal 30 -‐36 g/dl • CVS à Tachycardia, apex beat, auscultate for murmur in L+ 2nd ICs,
Blood Normal Fe Def. Folate / cardiomegaly, carotid bruit
Indices B12 Def • R.S. à Breath sounds infections.
• P.A à Organomegaly à Liver, spleen
MCV (fl) 75 - 100 < 75 140/110 • LAB INV à Hb%, TC, D.C, peripheral smear.
• B/U, S.Creatinine, S/Bilirubin, ECG, CXR, urine – routine
MCH (pg) 24 - 33 < 25 33/40
• Elective surgery: Major surgeries postponed and treated with iron, vitamin
MCHC(%) 30 - 36 < 30 32/38 B12, folic acid if Hb < 7 g/dl.
• Biochemical INV ! Megaloblastic IDA • Blood transfusion considered it should be completed 48 hrs prior to surgery.
Serum iron ! Serum vitamin B12 assay • Packed RBC preferred to whole blood.
T.I.B.C.! ! Serum folate assay • Transfusion of RBC à to ↑O2 carrying capacity, not for volume expansion.
S. ferritin ! ! Schilling test • Fresh blood preferred to stored blood (2, 3 DPG less) transfusion of 1 unit
whole blood à increases Hb by 1 g/dl/ Hct by 3%.
• Packed RBC produce twice increase in Hb compared to whole blood basis for
decision for preoperative transfusion à duration and etiology of anemia
intravascular fluid volume urgency of surgery.
• Likely blood loss co-existing diseases à myocardial ischemia, lung disease,
cerebrovascular disease.
• Emergency surgery: No time to correct anemia patient scheduled for surgery
without delay.
• Premedication à Benzodiazepines – Ex: Diazepam 0.01-0.2 mg/kg.
• Narcotic drugs low dose (because Respiratory depression) avoid atropine.
61

General anesthesia:
Aim: To minimize significant changes which interfere with O2
Preoxygenation:
delivery. To tissues.
1. Inspired O2 tension à adequate à for full saturation • Using high FIO2 (100%).
2. Avoid all drugs which induce fall in cardiac output • To optimize PaO2
Induction:
3. Avoid a shift to left of ODC à Eg. Hyperventilation
• If normovolemic à propofol à 1.5 – 2.5 mg/kg , thiopentone 3-5 mg/kg
4. Careful positioning à avoid peripheral pooling
for intubation à scoline 1-2 mg/kg midazolam à 0.1 – 0.3 mg/kg.
5. Quick blood transfusion
• Maintenance à with very low levels of inhalational anesthetic s (because
6. Slow and smooth induction
depression of myocardial). Less soluble in plasma of anemic patient (↓
7. Use of tourniquet à to ↓ operative blood loss
lipid rich RBC).
8. Avoid hypothermia, acidosis, hypoxia and dehydration Nitrous oxide avoided in megaloblastic and aplastic anemia:
• Oxygen à FiO2 – 50%
Monitoring:
• Controlled ventilation with non depolarizing relaxant.
• Pulse,
• Vecuronium à cardiostable avoid drug causing tachycardia like
• B.P. pancuronium
• pulse oximetry
• Extubation à after complete reversal and fully awake patient
• ECG, glycopyrrolate preferred to atropine.
• ABG,
• CVP,
urine output. Postoperative management:
•
• Avoidance of hypoxemia à O2 given in first 24 hr with FiO2 30-50%
Regional anesthesia : • Avoidance of hypovolemia à correct with blood transfusion,
• Spinal if patient is normovolaemic & has no tachycardia, crystalloids 3:1, colloids 1:1
precaution during preloading, epidural anesthesia • Avoidance of hypothermia, hyperthermia, convulsion.
preferred to spinal, local blocks preferred for limb surgery • Affect O2 supply / demand ratio. Patient kept warm.
supplement with O2 and adequate sedation. • To avoid shivering
• Avoid regional blocks if Hb < 8 gm/dl • Avoidance of pain, as pain à tachycardia à increased O2 demand à
• Avoid regional anesthesia in megaloblastic anemia with adequate postoperative analgesia.
neurological changes. • N2O inhibits the activity of methionine synthetase by oxidizing the
cobalt atom of vitamin B12 from an active to inactive state.
• Even relatively short exposures to N2O may produce megaloblastic
changes methionine synthetase is needed for cell division.
62

24. Autologous Blood transfusion. Dr Azam’s Notes in Anesthesiology 2013
• Autologous blood transfusion is one in which both donor as Patients with cardiac disease:
well as recipient are the same. 1. Absolute contraindications to pre-deposited are
• There are 4 types of autologous transfusion. The 2. Significant aortic stenosis
advantages and disadvantages, applications and 3. prolonged and / or frequent unstable angina
complications vary with the techniques being used. It is often 4. Significant narrowing of the left main coronary artery.
appropriate to employ more than one technique for patients 5. Cyanotic heart disease
undergoing surgical procedures associated with significant 6. Uncontrolled hypotension
blood loss. Loss of consciousness:
• Patients who have previously been blood donors and have had a
Types of autologous blood transfusion: prolonged fainting attack should not be accepted.
I. Preoperative blood donation Impaired placental blood flow:
II. Intraoperative blood salvage • Pregnant patients should not pre-donate if they are suffering from a
III. Postoperative blood salvage disease, such as hypertension; pre-eclamptic toxemia or diabetes
IV. Isovolumic haemodilution mellitus, which is associated with impaired placental flow and / or
I. PREOPERATIVE BLOOD DONATION: intrauterine growth retardation.
• In suitable cases, approx. 70% of patients can have their
total surgical blood requirement satisfied using pre- Method:
deposited donation. • Patients can donate 450ml of blood at weekly intervals; the last
i) Patient selection: donation being at-least 4 days and preferably 1 week prior to surgery.
• The criteria for pre-deposited donations are less strict than • They should commence oral iron prior to their first donation and
those for normal homologous blood donors. The continue until the day of surgery. Adults weighing less than 50kg and
haemoglobin concentration should normally be greater than pediatric patients require special consideration.
11gm/dl and never below 10gm/dl. • The volume withdrawn at any one time should not exceed 12 percent of
the Pts estimated blood volume.
ii)Contraindications: • They should have blood drawn into pedipack containing 35ml of
! !"#$%&'()"#&*$)+'$,-&"#$.,'' anticoagulant and which are suitable for collection of up to 250ml of
/)*0$)"'0$1&)1&'' blood.
2.11'.-'".,1"$.31,&11'' • The physiological response in patients taking β-blockers and / or ACE
inhibitors is compromised by their treatment, they should therefore be
456)$*&0'6+)"&,#)+'(+..0'-+.7'8'9:;<'=>:<'?@''
given isovolumic crystalloid replacement to minimize the hazardous
sequelae, which may follow a sudden reduction in blood volume, when
Active bacterial infection:
donating late in pregnancy; patients should be in the lateral position
• Patients who have active infections septic, if such blood is because of the weight of the uterus impedes the venous return when
drawn, the bacteria may proliferate during storage, leading
the patients is lying on her back.
to fatal reactions.
63

Autologous Blood transfusion.Continuation: Dr Azam’s Notes in Anesthesiology 2013
INTRAOPERATIVE BLOOD SALVAGE: 1) Disposable reservoirs: Shed blood is aspirated using a vacuum
• Pre-deposit donation is limited by the time that the blood can pressure of less than 150mm Hg into a single- use self contained
be stored and by the ability of patients to donate at frequent disposable reservoir. Unless the patient has been anticoagulated prior to
intervals. Isovolumic hemodilution or acute normovolemic surgery, the blood should be anticoagulated using citrate. When the
hemodilution (ANH) is limited by the patients total blood reservoir is full, the blood can either be immediately re-infused by gravity
volume and by hemodynamic considerations. Postoperative using a standard given set and microaggregate filter, or stored until room
salvage is limited by mechanical problems and possible temperature, until required.
bacterial contamination intraoperative cell salvage (ICS) in Advantage – being cheap and requiring no specialized equipment or
contrast, can be used throughout the surgical procedure and specially trained personnel.
is able to replace blood in proportion to the amount lost. Disadvantage – slow, only suitable for small volumes and the product is
Methods and equipment: unwashed and has a low hematocrit.
• The basis of ICS is to collect shed blood from the operative 2) Canister collection: The blood is aspirated, via a double lumen sucker
field; into a sterile container where the blood may or may not that allows anticoagulant to be mixed at the sucker tip, through a 170µm
be further processed; prior to returning it to the patient. To filter into a rigid reservoir containing a disposable liner. When the canister
prevent the blood clotting; either the patient has to be is full, the liner is removed and the blood re-infused through a standard
anticoagulated prior to the operation, or anticoagulant has to transfusion set and microaggregate filter. Prior to reinfusion the blood can
be added to the blood at the sucker tip. Anticoagulation be washed using a standard cell washer which is usually situated in the
cannot be delayed until the blood has arrived in the container blood bank.
because, unlike the situation in normal blood donation, the 3) Semi continuous flow centrifugation: Blood is aspirated, using a double
coagulation factors have been activated in the operative lumen sucker, into a reservoir. The blood is washed, with saline prior to
field. being re-infused. There are two varieties of equipment available, the so
The main steps of this technique are called slow flow machines which produce one unit every 7-10 mins and
1. Salvaging the blood from the operative site. the fast flow system which produce a unit in less than 3 mins.
2. Anti-coagulating the whole blood – prior to surgery during To avoid hemolysis the following precautions should be taken
suction. 1. Blood should be aspirated by placing the tip below the surface of the
3. Re-infusing whole blood as such after filtering or re-infusing blood. The surgeon must avoid skimming, as aspiration of air with the
the red cells after washing. blood will lead to turbulence and hemolysis.
2. The sucker should have a plastic tip with multiple holes. This is
There are three basic methods for ICs: especially important during orthopedic surgery as aspirated debris
I. Semi continuous flow centrifugation may occlude some of the holes, thereby increasing turbulence.
II. Canister collection
III. Single use disposable reservoirs
64

Anticoagulant:
• Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration of 30,000
units per lt of saline, with 15ml of heparin / saline being added to each
100 ml of blood (ratio heparin to blood, 1:7).
Wash solution:
• The volume of saline wash solution should be three to four times that of
the volume of the blood, although for orthopedic cases this may be
increased to six to seven times with a minimum volume of 150ml.
Re-infusion:
• The blood must be re-infused using a standard blood filter with or
without a microaggregate filter.
INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
1) Cardiovascular:
• The canister collection method should be used when the anticipated
blood loss is less than 1500ml when greater loss is expected, a semi
continuous flow centrifugal method is preferred.
2) Vascular surgery:
• Both in the reconstruction of an aortic aneurysm and in the treatment of
aortic rupture there is requirement for rapid salvage and returns of
blood. In these cases, fast flow instruments are usually best.
3) Orthopedic: Hip and spinal surgery
• In hip and spinal surgery, the use of ICS, especially when combined
with pre-deposit elevation can usually avoid the need for homologous
blood.
4) Liver transplantation
5) Neurosurgery – AVM: ICS is used during the refashioning of
arteriovenous malformations.
65

6) Trauma Washed saline suspended red cells:

7) Ectopic pregnancy: • Typically 10% of the red cells are hemolyzed and lost in the washing
• Thorough washing of the blood is required to prevent the procedure. The level of free Hb in the salvaged blood will be between
reinfusion of amniotic fluid leading to emboli and DIC. 200 and 500mg/dl although washing removes 50-70% of this. The
8) Plastic surgery MCV, MCH, MCHC are normal and the majority of the cells are
9) Jehovahʼs witnesses morphologically normal. The hematocrit to re-infused product is
10) Serological antibodies: between 45 and 65%. Platelet numbers are reduced and their function
• Patients with rare and / or multiple serological antibodies is grossly impaired, probably due to the release of β-thromboglobulin.
and / or other cross-match problems can be candidates for Washing removes all the plasma proteins, including most of the clotting
ICS. factors as well as most of the anticoagulant. Although complement
Contraindications: activation occurs during cell salvage the washed product is complement
1. Retrieval of blood from infective sites and from abdomen free.
with fecal soiling is to be avoided. This should be done only Unprocessed salvaged blood:
as a last resort as it carries a high risk of bacteremia and • As this blood is not concentrated, the Hb level is between 7 and 9g/dl
septicemia. This can be minimized to a certain extent by and is sometimes as low as 4g/dl. The plasma Hb is normally in the
prophylactic antibiotics. range of 60-250 mg/dl but may be upto 2000 mg/dl. There is marked
2. Blood containing significant amounts of amniotic fluid increase in fibrin degradation products and D-dimers. Anticoagulant is
should not be auto transfused. added to the shed blood as it is aspirated from the operative field and
3. Blood containing wound irrigants such as Betadine; this is not removed during processing. Concentrations of heparin of 3
methylmethacrylate, antibiotics not meant for parenteral iu/ml and higher have been found in the re-infused blood.
use and topical haemostatic agents should not be
salvaged. COMPLICATIONS:
Product: 1) Air embolism
• The product is immediately available at body temperature. 2) Reinfusion of hemolyzed red cells:
Blood collected by ICS has a high 2, 3 DPG content so that • If the vacuum pressure on the sucker is too high or excess turbulence
the haemoglobin can easily offload oxygen. The ODC is has been caused by improper aspiration technique, hemolyzed red
normal or even slightly right shifted, in contrast to that of cells can be re-infused into the patient.
homologous banked blood which is markedly left shifted and 3) Coagulation disorders
normal oxygen release is not achieved for 6-12 hours post 4) Thrombocytopenia
transfusion. ICS red cells have increased osmotic resistance 5) Hypocalcaemia
with an excellent 24-hour post transfusion survival, and a 7) Toxic antibiotic effects
normal cell life (T ½ - 24 days). This may be because only 8) Microfibrillar collagen haemostatic material
the younger and fitter cells survive the collection and These products promote platelet adherence and aggregation leading to
washing procedure. local hemostasis.
66

POST OPERATIVE BLOOD SALVAGE: ACUTE NORMOVOLAEMIC HEMODILUTION:

• This method is mainly used after cardiothoracic surgery and • Haemodilution is defined as a dilution of all blood constituents resulting
sometimes after joint replacements. The suction drain is from a limited exchange of the patientʼs whole blood for cell free plasma
connected either to a disposable collection device or to a like fluid.
cardiotomy reservoir. Anticoagulation is seldom required as • The phrase “isovolemic hemodilution” indicates dilution of the blood
the blood is defibrinated within the mediastinum, but if the while keeping the circulating blood volume constant. Hematocrit is the
bleeding is brisk, citrate should be added to the container. parameter used to define the degree of haemodilution.
The vacuum pressure should be between 0 and 40 mm Hg. • Limited or moderate preop haemodilution means an intentional
Because of the dangers of bacterial contamination the time reduction of the Hct from its normal value of 0.30-0.25 immediately prior
between the start of collection and reinfusion should be less to surgery and is used to minimize the loss of autologous red cells and
than 6 hours. The product contains no clotting factors, plasma components during surgery.
including fibrinogen, has a hematocrit of 15-20% and Contraindications to acute normovolaemic hemodilution:
contains considerable free haemoglobin and products of clot 1. Hematocrit less than 24%.
lysis when volumes greater than 800ml of unwashed blood 2. Patients with limited ability to increase cardiac output such as valvular
are re-infused. It has been shown that platelet function is heart disease and intra or extra cardiac shunting.
deranged and the patient develops a mild coagulopathy. 3. Patients with respiratory insufficiency needing mechanical ventilation.
Others complications include prolongation of thrombin time; 4. Patients with haemostatic defects.
upper airway oedema requiring intubation; non-cardiogenic Compensatory mechanisms during hemodilution:
pulmonary oedema due to platelet and complement a) Blood Rheology:
activation leading to the capillary leak phenomenon. • According to the Poiseuilleʼs-Hagen law, the resistance to laminar flow
of a fluid is inversely proportional to the fourth power of the radius but
POST TRAUMATIC SALVAGE: directly proportional to the viscosity of the fluid and length of the tube.
• Following chest or abdominal trauma, blood collected in • According to the Poiseuilleʼs-Hagen law, the resistance to laminar flow
aerosal cavities is devoid of fibrinogen and hence does not of a fluid is inversely proportional to the fourth power of the radius but
clot. This can be salvaged and auto transfused and maybe a directly proportional to the viscosity of the fluid and length of the tube.
life saving procedure in many situation. Q = (P1 - P2) X π r4 / 8 nl
• Q = flow; (P1 – P2) = pressure drop across the tube; l = length of the
tube; r = radius of the tube ; η = viscosity of the fluid. However this
law deals only with laminar flow in a straight rigid tube.
67

• Initial losses of energy may be considerable when flow is Effect on organ systems:
constantly changing and these losses do increase with i) Cardiac: The heart must increase its output as this is the main adaptive
extensive hemodilution which leads to an increased bulk flow mechanism of hemodilution compensation is achieved mainly by an
and an augmented kinetic energy of the blood. Turbulence is increase in coronary flow rates. Coronary vasodilatation is also important
more likely to occur if the linear flow rate is increased and to meet the increased demand.
viscosity of blood is lowered; both of which are changes ii) Cerebral: Cerebral blood flow increases during hemodilution and
initiated by hemodilution. normal oxygen delivery is maintained without cerebral vasodilatation.
• In hemodilution, there is a decreased red cell aggregation Hyperventilation results are hypocapnia which decreases cerebral blood
and dilution of proteins like fibrinogen, hence the viscosity is flow and thus should be avoided during hemodilution.
reduced. iii) Hepatic and gastrointestinal: Hepatic blood flow increases during
• In summary, haemodilution decreases the oxygen carrying acute isovolumic haemodilution in proportion to the cardiac output. As the
capacity of blood and decreases the resistance to flow. An liver receives some of its blood supply, as desaturated blood, it
optimal hematocrit for tissue oxygen delivery has been found compensates for this by an increased oxygen extraction. If intestinal
to be around 30%. ! blood flow decreases and oxygen extraction increases, hepatic oxygen
b) Utilization of oxygen: supply via the portal vein decreases. Centrilobular hepatic necrosis has
• Aerobic metabolism is maintained in a tissue despite a been reported at hematocrit value below 20%.
decrease in the circulating red cell mass as a result of two iv) Renal: Hemodilution causes renal vasoconstriction resulting in
compensatory mechanisms. redistribution of blood flow to the inner cortex and a reduction in the
1. Increased blood flow to the tissue fraction of cardiac output to the kidney. The large renal arteriovenous
2. Increased oxygen extraction oxygen content reserve prevents impairment of tissue oxygenation.
c) Autonomic effects: v) Pulmonary: Hemodilution does not alter pulmonary function or
• During hemodilution, there is peripheral to central ventilation / perfusion distribution. The alveolar to arterial oxygen tension
redistribution of blood mediated by alpha adrenergic difference decreases during hemodilution indicating better arterial
mechanism. This is basically a capacitance vessel response. oxygenation.
Contradictory results have been obtained regarding cardiac vi) Pregnancy: Hemodilution should be used with caution in pregnant
autonomic function in haemodilution. Hence this technique patients. This is primarily due to the fact that a low maternal
should be performed in caution in patients treated with hematocrit can result in inadequate oxygen content in the blood
autonomic blocking agents and in patients under spinal or perfusing the placenta.
epidural anesthesia.
Methods of producing isovolaemic haemodilution:
The diluent chosen must
1. Maintain the circulatory volume
2. Not adversely affect the Oxygen Dissociation Curve
3. Not affect the rheological properties of blood.
68

Crystalloids: • The above formula is applicable when blood is lost during surgery and
• Only a 3:1 crystalloid to blood replacement ratio is is substituted with an erythrocyte free fluid after the bleeding has
associated with an increased cardiac output with no change stopped. However, in haemodilution, the blood loss is being
in mean arterial pressure. simultaneously replaced by a cell free infusion. Hence during the
Colloids: constant exchange, the washout of the red cell decreases with time,
Composition Distribution this is described by the equation.
Distribution
and mean Intra Adv. Blood loss = estimated blood volume x In (H0/H1)
Colloid Interstitial half life
mol. Wt. vascular reactions Where H0 is the initial hematocrit, H1 is the final hematocrit and ʻInʼ is the
(vol%) (hours)
(Daltons) (vol%) natural logarithm. Since this is not very practical, a reasonable accurate
Albumin Albumin 20% 80% > 24 hrs Least equation is:
(69,000)
Dextran 70 Polysaccharid 0 100% 6-12 hrs Few if treated
e (70,000) with dextran
1 Blood loss =
Dextran40 Polysaccharid 0 100% 2-3 hrs Few if
e (40,000) pretreated The average hematocrit during haemodilution is calculated as the
Hetastarch Amylopectin 0 100% > 24 hrs Few
(450,000)
Gelatin Polypeptide 50% 50% 2-4 hrs Few average of critical hematocrit and final hematocrit is .
(polygeline) (35,000) • Blood can be drawn either under anesthesia or prior to induction of
anesthesia. Blood withdrawal rate must parallel the administration of
The amount of blood loss during isovolaemic hemodilution can appropriate diluent volumes to assure normovolaemic and circulatory
be calculated from the following equation- stability. Hematocrit measurement midway throughout surgery prevents
over dilution. It is also measured at the end of haemodilution.
Blood loss =
• The estimated blood volume is generally taken as 70ml/kg in

females of normal body habitus. The decrease in hematocrit
is calculated as the difference between the initial hematocrit
and the final hematocrit after isovolumic haemodilution. The
haemoglobin concentration can be substituted for the
hematocrit values in the above equation.
69

Advantages of autologous transfusion: Disadvantage of autologous transfusion:

• Eliminates the risk of transfusion reaction. • Complex logistics for collection; storage and transfusion of the correct
• Eliminates the risk of disease transmission. unit to the appropriate patient.
• Eliminates the risk of alloimmunization to red cells, white • Only suitable for certain operative procedures.
cells, platelets or plasma proteins. • Tendency to over transfuse.
• Eliminates the risk of transfusion transmitted graft VS host • If the surgical procedure is delayed; the blood may become outdated.
disease. • Bacterial contamination
• Allows safe transfusions in patients with multiple • Patient is made grossly anemic by either too frequent pre-deposit
alloantibodies or with rare blood groups. donation or over hemodilution.
• Pre-deposit donation “stimulates” erythropoeisis prior to • Coagulation defects
surgery. • Incorrect techniques can cause red cell hemolysis.
• Hemodilution improves tissue oxygen perfusion by lowering • Equipment for intraoperative blood salvage is expensive and requires
the blood viscosity. trained staff.
• Provides blood cover for some Jehovahʼs witnesses. • Tends to give a misguided impression that normal homologous
• Provides readily available blood in cases of major donations are unsafe.
hemorrhages.
• Reduces the demand on homologous blood supply in remote Precautions:
areas or developing countries. • Agents such as atropine and pancuronium which cause tachycardia are
• Gives patients the psychological benefit of activity best avoided. Monitoring should include ECG: urine output;
participating in their treatment. temperature, central venous pressure and preferably invasive arterial
pressure. Ventilation should be adjusted to prevent acidosis or a left
ward shift of the ODC caused by alkalosis resulting from
hyperventilation.
• Blood is drawn into standard bags containing acid citrate dextrose
(ACD) solution and stored at room temperature. Reinfusion of the
patientʼs blood should ideally be undertaken when operative bleeding
has ceased. Units of blood which were drawn last should be transfused
first. A filter should not be used in the administration set.
70

25. Massive Blood Transfusion. Dr Azam’s Notes in Anesthesiology 2013
Definition: • Needles and sharp objects should be handled and disposed of carefully
• Massive blood transfusion may be defined either as the to avoid needle stick injury.
acute administration of more than 1.5 times the patients total • Wearing of gloves is recommended, to prevent contamination of hands
blood volume by homologous blood in less than 24 hours. with spilled blood.
• Also defined as transfusion of one pint of blood with in 5 • Use of 3-way taps with or without extension tubing reduces the need to
minutes; or transfusion of 5 units within 1 hr or transfusion of use needles for drug administration or blood sampling.
10 units within 6hrs, or transfusion of >10% of blood volume
within 10 minutes. Pressure bags, blood warming and rapid infusion devices:
Precautions: • Major haemorrhage may require the transfusion of blood at fast flow
• At least 2 large gauge venous cannula (12 gauge) should be rates (upto 500ml/min) and at temperatures greater than 35 °C.
secured; solely for the purpose of blood transfusion. • This can be achieved by using a constant pressure infusion device
• If peripheral venous access is difficult, cannula may be combined with an efficient blood warmer and a purpose designed
inserted into a large, central vein such as the subclavian, double length blood warming coil.
internal jugular or femoral vein. A venous cut down may also • Efficient counter current aluminum heat exchanges have been
be alternatively performed in the saphenous vein at the investigated under conditions of high flow and have been found to be
ankle. effective.
• In addition an arterial catheter and triple lumen central • Priming or flushing blood through the system with fluids containing
venous catheter may be useful in allowing rapid blood calcium (such as compound sodium lactate and haemacel) should be
sampling and direct measurement of arterial and central avoided, as this may result in blood clot formation in the tubing. This is
venous pressures respectively. The triple lumen catheter due to the reversal of the anticoagulant effect of citrate by calcium ions.
also provides access for intermittent bolus administration of • The hematinics rapid infuser device has a 3 litre reservoir into which
drugs or drug infusions. cell saved or banked blood and FFP can be stored, warmed and
• Alternatively (or in addition) a sheath introducer (8 French infused at rates of upto 2l/min.
gauge) may be inserted into the central vein; providing a • If such equipment for rapid transfusion is not available the speed of
large cannula for transfusion and means whereby a transfusion can be increased by simple maneuvers for e.g. increasing
pulmonary artery catheter can be inserted, when indicated. height of fluid above the patient or using intermittent manual
• Unless contraindicated by pelvic or urethral injury; a urethral compression of the lower chamber of the giving set when full of fluid.
catheter should be passed and urine output measured Alternatively using a large syringe and a 3-way tap in line; fluid can be
(intermittently) hourly. drawn rapidly into the syringe from the giving set before being
• Central and peripheral temperature should be recorded. administered to the patient through the 3-way tap.
• Pulse oximeter – for heart rate and oxygen saturation. • A manually operated Martinʼs rotatory pump may be used (not available
now)
71

Massive Blood Transfusion.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Complications: 2) Citrate toxicity:↓ in ionized calcium

1) Coagulation changes: • Each unit of blood contains approx. 3gms of citrate as an anticoagulant.
• In situations other than those of liver transplantation and in In normal circumstances the liver metabolizes this rapidly. Liver
patients with a pre-existing coagulopathy; it is unusual for a metabolism must be impaired before citrate metabolism becomes
significant reduction of plasma coagulation factors to occur overwhelmed.
solely as a result of massive transfusion of stored whole • Citrate binds to ionized calcium fraction in blood and causes a
blood. decrease in myocardial function, hypotension, small pulse pressure and
• Stored whole blood contains adequate amounts of increased diastolic and central venous pressures.
coagulation factors I, II, VII, IX, X, XI and XII. Concentrations • Transient changes in ionized calcium concentrations causes little
of factors V and VII are reduced in stored blood. hemodynamic disturbance and the routine use of calcium with blood
transfusion is not recommended unless hepatic function is
Causes of coagulopathy after massive blood transfusion; compromised. This may be caused by a low cardiac output;
1. Preexisting defects caused by the underlying disease or hypothermia; liver d/s; or liver transplantation and in these situations,
drugs used. chances of developing a decreased calcium concentration and citrate
2. Dilution by replacement therapy. toxicity is increased.
3. Artificial plasma expanders e.g. dextran and hydroxyethyl • Calcium also plays a role in both extrinsic and intrinsic coagulation
starch. pathways. A bleeding diathesis associated with hypocalcaemia is
4. Stress uncommon as cardiac arrest is said to occur before the plasma
5. Tissue injury concentration decreases to a value that affects coagulation.
6. Shock
7. Bacteremia Treatment:
• In patients with severe liver disease; the pre-existing • The adverse effects of hypocalcaemia can be treated by administration
coagulopathy consists of a decrease in platelet count and all of calcium chloride if the patients become hypotensive and is not
coagulation factors except factors I and V (because of a hypovolemia; or on the basis of a measured decrease in plasma
decrease in synthetic ability of liver). This leads to increased concentration of ionized calcium.
prothrombin time (PT) and APTT. • Calcium gluconate is less effective than calcium chloride because it
Treatment: must be metabolized to be effective.
• Administration of platelets and FFP
• Dose: 1 Unit of FFP for every 10 kg
• 2 unit FFP for each 10unit of blood transfused
• 6 unit Platelet concentration for every 20u of blood
transfused
• Basic screening tests for bleeding after operation-- Platelet
count; prothrombin time; APTT; plasma fibrinogen
concentration and fibrinogen degradation products when
indicated.
72

3) Potassium: Treatment:
• K+ in stored blood increases to almost 30mmol/l after 3 I. Placing patient on a heated “ripple” mattress
weeks of storage. After transfusion, viable RBC establishes II. Warming IV fluids
their ionic pumping mechanism and intracellular reuptake of III. Covering patient with thermally insulating drapes.
K+ occurs. IV. In small children, an overhead infra-red heater minimizes heat loss
• Transient hyperkalemia has been observed during massive from radiation.
blood transfusion and correlates strongly with the rate of V. The ambient temperature of the theatre may be increased.
transfusion. Therefore ECG monitoring is advisable during
massive blood transfusions. 6) Pulmonary dysfunction: TRALI
4) Acid-base disturbances: • Pulmonary dysfunction after transfusion is caused or exacerbated by
• 3 week old stored blood (citrated) contains an acid load of the formation and subsequent administration micro-aggregates formed
upto 30-40 mmol/l and this originates mainly from the citric in stored blood.
acid of the anticoagulant and lactic acid generated by red • They are composed largely of degenerating platelets; granulocytes;
cells during storage. denatured proteins; fibrin strands and other debris and their rate of
• Citrate is metabolized to bicarbonate and may produce a formation and size (10-200μm in diameter) vary according to the
profound metabolic alkalosis after transfusion because of this different types of storage solutions.
it is not necessary to correct minor degrees of metabolic • Blood filters have been designed to remove micro-aggregates and are
acidosis. of 2 types.
• Shocked patients more likely to develop metabolic acidosis. • Depth filters: which remove particles by impaction and adsorption
5) Hypothermia: • Screen filters: which operate on a direct interception principle and have
• The problems attributable to hypothermia include reduction an absolute poor size rating of 40µm (the standard blood administration
in citrate and lactate metabolism (thereby increasing the set has a pore size of 170µm).
probability that patient will develop hypocalcaemia and BLOOD TRANSFUSION REACTIONS
metabolic acidosis during transfusion); an increase in the • Major life threatening complications following blood transfusion are rare
affinity of Hb for O2; impairment of red cell deformity; platelet and human error remains an important etiological factors in many.
dysfunction and bleeding and an increased tendency to • Complications that can accompany administration of blood / blood
cardiac arrhythmias. components include
• Therefore core temperature measurement is important I. Transfusion reactions
during massive blood transfusion and can be measured with II. Metabolic abnormalities – H+, K+, citrate
a temperature probe at the midpoint of the oesophagus. III. Transmission of diseases – hepatitis, HIV, viral, bacterial protozoal
• Body temperature may decrease because of administration IV. Microaggregate infusion – post transfusion pulmonary dysfunction.
of large volumes of cold fluids and blood (which is stored at
40C) or because of loss of radiant heat and latent heat of
evaporation of body fluids from the open abdominal or
thoracic cavity or skin (especially in burn patients).
73

I. Transfusion reactions: 2) Febrile reactions:

Immediate reactions: • Are the most common non hemolytic reaction. This is due to interaction
1. Febrile reactions (due to ab. to donor, leukocyte Ag) between Abs and Agʼs present in leucocytes and or platelets of the
2. Hemolytic (red cell incompatibility donor. Fever results from the release of pyrogenic substances from
3. Anaphylaxis (Ab to IgA of donor) injured cells.
4. Urticaria (allergic – due to Ab to plasma proteins) • Body temperature may increase within 4 hrs after starting the
5. Non-cardiogenic pulmonary oedema (donor antibodies transfusion. Headache, nausea, vomiting and chest or back pain may
to pt. leucocytes) accompany the elevation of body temperature. Treatment of mild febrile
6. Fever with shock (bacterial) reactions is by slowing the rate of infusion of blood and by
7. CCF (fluid overload) administration of paracetamol. Pethidine 25mg iv to adults, is useful for
Delayed reactions: the treatment of shivering which may accompany the reactions –
1. Hemolysis severe febrile reactions may require discontinuation of the blood
2. GVHD infusion.
3. Purpura 3) Hemolytic reactions:
4. Alloimmunization Hemolytic reactions are almost mainly due to ABO incompatibility.
1) Allergic reactions: Although rare, they are a major cause of transfusion associated mortality.
• Can occur in 3% of correctly typed and cross matched blood • The quantity of antibody in acute hemolytic reactions appear to
transfusion. Incompatible plasma proteins (Haptogens) are determine the resultant morbidity and mortality.
the probable cause. Manifestations include pruritis, erythema • Group O recipients have both anti A and B in their plasma. If group O
and urticaria often accompanied by increase in body recipient, receive type A, B or AB blood, the biological consequences of
temperature and eosinophilia. Rarely laryngospasm and this incompatibility to the patient are greater than after a small volume
bronchospasm are also present. Under anesthesia the first of donor plasma containing antibodies directed against the recipient
manifestation of allergic reactions due to blood transfusion cells is transfused (i.e. group O to a recipient of group A, B or AB).
may be the appearance of erythema along the pathway of • The Ag-Ab interaction activates the complement cascade and this
the vein receiving the blood plus urticaria particularly on the results in lysis of donor cells – intravascular hemolysis.
chest, neck, face. • Complement activation results in release of complement fragments (C3,
• Serious anaphylactic reactions are most likely to occur in C5) and histamine which are potent vasodilating compounds and
patients who lack IgA. These patients have an anti IgA and enhance capillary permeability. This leads to hypotension.
can develop severe allergic reactions when they are • DIC is initiated by material released from hemolyzed erythrocytes,
administered serum containing IgA such patients should leading to thrombocytopenia and increased circulatory concentrations
receive transfusion only from IgA deficient donors. of fibrin degradation products.
• Elevation of unconjugated fractions of bilirubin in plasma are maximal
3-6 hrs after the onset of hemolytic reactions.
• Renal damage resulting in acute renal failure is a consequence of
multiple factors including:
74

1. Glomerular deposition of fibrin. • As little as 50ml of incompatible blood may exceed the binding capacity
2. Reduced renal blood flow, due to histamine induced of haemoglobin, which is a protein that can bind about 100mg of
vasomotor changes. hemoglobin per 100ml of plasma. When hemoglobin not exceeding this
3. Precipitation of stromal and lipid contents and erythrocytes amount is injected or liberated into the blood stream, the Hb circulates
in distal renal tubules. as a complex with the haptoglobin, which is cleared by the
4. Free Hb does not directly damage the kidneys but can reticuloendothelial system. A sample of plasma that contains 2mg/dl of
contribute to renal failure if it is precipitated in the renal haemoglobin is faintly pink or light brown. When the level of Hb reaches
tubules and blocks the tubules. 100mg/dl, then the plasma is red. When the plasma hemoglobin
5. Acute tubular necrosis – results from Ag-Ab reactions à reaches 150mg/dl, hemoglobinuria occurs. In general, the quantity of
release of tonic substances from RBC à vasoconstriction. free haemoglobin in the plasma is correlated with the volume of
In the anaesthetized patient, the immediate signs and incompatible blood transfused.
symptoms of hemolytic reactions are masked. Hypotension Lab tests that should be performed if hemolytic transfusion reactions are
and abnormal bleeding may be the only finding. suspected include
• Serum haptoglobin
Schematic representation of what happens to hemolyzed • Plasma and urine haemoglobin
erythrocytes as a result of the administration of incompatible • Bilirubin
blood:
• Direct antiglobulin-confirms the presence of hemolytic transfusion
! reaction because it shows that there is antibody attached to transfused
!
"#$! "#$! donor red blood cells.
h) Signs and symptoms of hemolytic transfusion reaction:

• Fever and chills
%&''!()'*+,-+./0!
• Chest pain
• Hypotension
• Nausea
1)'*+,-+./02()34+,-+./0! </=0'>!! • Flushing
5+*3-'6!! • Dyspnoea
!!!!!!!!!!!!!!!7899*,:;! • Hemoglobinuria
!
"'4/5?-+2'0=+4('-/)-!
@>@4'*!!
75

The treatment of a hemolytic transfusion reaction: II. Metabolic abnormalities:

• Stop transfusion Metabolic abnormalities produced by administration of blood are related
• Maintain the urine output at a minimum of 75-100ml/hr by the to changes that occur during storage.
following methods: • Hydrogen ions: 30mmol/L after 3 weeks
1. Generously administer fluids intravenously and possibly • Hydrogen ion content of stored blood is initially increased by the
mannitol 12.5 to 50gm given over a 5 to 15 min period. addition of ACD (pH. 5) or CPD (pH 5.5) causing the pH of freshly
2. If intravenously administered fluids and mannitol are drawn blood to decrease to 7-7.1. Continued metabolic function of
ineffective then administer furosemide 20-40 mg/hr. erythrocytes results in additional production of hydrogen ions.
3. Alkalinize the urine, because bicarbonate is • Furthermore CO2 partial pressure increases between 150mmHg and
preferentially excreted in the urine; only 40-70mEq/70kg 200mmHg since this gas cannot diffuse through glass or plastic
of body wt. Sodium bicarbonate is usually required to containers.
raise the urine pH to 8. Where upon repeat urine pH • Despite these changes, metabolic acidosis is not a common,
determinations indicate the need for additional occurrence, even with the rapid infusion of large volumes of stored
bicarbonate. blood.
4. Assay urine and plasma Hb concentrations. • Metabolic alkalosis, rather than metabolic acidosis, is a frequent
5. Determine platelet count; partial thromboplastin time accompaniment of massive blood transfusion. This alkalosis is
and serum fibrinogen level. preserved to be partly due to metabolism of infused citrate to
6. Return unused blood to blood bank for re-cross match. bicarbonate, which could further be exaggerated by administration of
7. Send patient blood and urine sample to blood bank for lactated ringerʼs solution.
examination. Potassium:
8. Prevent hypotension to ensure adequate renal blood • Potassium content of ACD blood reaches about 14mEq/l by 7 days of
flow. storage and increases further to 21mEq/l to 24 mEq/l after 21 days.
9. Maintain IV line, O2 therapy; resuscitative measures. Potassium levels of blood stored in CPD are about 20% lower. Still,
10. Antihistamine – diphenhydramine 0.5-1mg/kg IV. nevertheless, massive transfusions of stored blood rarely increase
11. Steroid – hydrocortisone – 2-4mg/kg IV. plasma concentration of potassium.
12. Antibiotics. • The metabolic alkalosis produced by massive transfusions of whole
blood favor transfer of K+ from extracellular fluid into intracellular
spaces, offsetting any tendency toward hyperkalemia. However, in
patients with impaired or absent renal function, transfusion of blood
could produce hyperkalemia.
76

Decreased 2, 3 diphosphoglycerate: III. Transmission of diseases:

• Normal storage of blood results in progressive reductions in a) Hepatitis:
concentrations of 2, 3 DPG in erythrocytes resulting in • Remains the infection most frequently transmitted by blood and its
increased affinity of Hb for oxygen. This results in the shift of products. Icteric hepatitis develops 50-180 days after a blood
ODC to the left which could jeopardize tissue O2 delivery, transfusion and has a variable clinical course, ranging from being
particularly in the presence of anemia. The high pH of CPD asymptomatic to being fatal.
anticoagulant, as compared to ACD anticoagulant, prevents Diagnosis by:
rapid depletion of 2,3 DPG concentration in erythrocytes. • Observation between 14 to 180 days transfusion of 2 consecutive
The P50 of CPD preserved blood is maintained at near elevations (minimum of 14 days apart) of recipients ALT.
normal levels for 1st 2 weeks of storage. • Diagnosis of hepatitis B includes appearance of hepatitis B surface
antigen; the hepatitis B surface or core antibody.
Citrate intoxication: • The absence of serological markers indicative of acute hepatitis A or B
Hypocalcaemia: in the presence of liver enzymes abnormalities are taken as
• Citrate intoxication is not caused by the citrate ion per se, but presumptive evidence of “non-A-non B” viral hepatitis, now called
because citrate binds calcium. hepatitis ʻCʼ, the most common causative agent of post transfusion
• Manifestations of hypocalcaemia due to citrate intoxication hepatitis.
include hypotension and prolonged Q-T intervals in ECG; - Precautions taken to avoid hepatitis transmission are exclusion of
reflecting mobilization of Ca2+ stores in bone and the ability blood with elevated serum alanine aminotransferase (ALT) or
of liver to metabolize citrate to bicarbonate rapidly. presence of Abs to hepatitis B is antigen. !
• The rate of whole blood transfusion in adults has exceeded b) Acquired immunodeficiency syndrome (AIDS):
150ml/70kg/minute or 1 unit of whole blood in 5 mins before • Risk of AIDS from blood transfusion is very low, owing to the treating of
reduction in plasma ionized calcium can be documented. donor units for the Ab to the human immunodeficiency virus. However
Therefore arbitrary administration of calcium is not indicated. the infections period does occur during the 12 weeks necessary for HIV
• Although hypocalcaemia due to citrate intoxication is unlikely seroconversion. Some infected individuals have a much greater latency
in adults the same is not true of neonates receiving blood period (35 months).
transfusion and supplemental calcium may be necessary.
• In the presence of hypothermia or marked liver dysfunction
the ability to metabolize citrate to bicarbonate may be
reduced.
• The usual dose of calcium chloride is 3-6mg/kg administered
over 5-15 mins with continuous ECG monitoring.
77

7.
6.
5.
4.
3.
2.
1.
Viral:
HIV-2
HIV-1
Brucella !
Parasitic:
Bacterial:
HTLV I/II
Trypanosoma
Microfilaria ! !
Salmonella ! !
!
Herpes simplex !
Cytomegalovirus !
HIV Ag (P&H Ag)

!
!
!
!
!
Hepatitis (antibody)
IV. Micro-aggregate infusion

Ab to hepatitis B core Ag
through blood transfusion are;
Serological tests for syphilis

- Shigella
- Measles
- Plasmodium
Accumulation of these microaggregates
necessary for whole blood < 3 days old.

remove particles with diameter in the 10
• Micropore filters have been developed to
become significant after 2-5days and can
- Pseudomonas
The other infections that can be transmitted
Massive Blood Transfusion.Continuation:
• Microaggregates consisting of platelets and

- Epstein barr virus
micron to 40μ range. Micropore fitters are not

cause post transfusion pulmonary dysfunction.
leucocytes form during storage of whole blood.
Infectious disease testing for blood transfusions:
Table 3—Elemental Calcium Concentrations in Calcium Chloride and Calcium Gluconate
Solution Elemental Calcium Unit Volume Total Elemental Calcium Osmolarity

10% Calcium chloride 27 mg (1.36 mEq)/mL 10 mL Ampule 270 mg/ 10 mL 2000 mOsm/L
10% Calcium gluconate 9 mg (0.46 mEq)/mL 10 mL Ampule 90 mg/ 10 mL 680 mOsm/L
10% Calcium chloride continuous infusion 2.45 mg/mL 5 Amps/500 mL NS 1,350 mg/ 550 mL 200 mOsm/L
10% Calcium gluconate continuous infusion 0.82 mg/mL 5 Amps/500 mL NS 450 mg/ 550 mL 200 mOsm/L
Amps 5 ampules; NS 5 normal saline. (Adapted with permission from Stratta et al.42)
It is important to recognize the differences in ele- polymerization with a decrease in pH from 7.4
mental calcium that calcium chloride and calcium to 6.8.47
gluconate provide (Table 3).42 As elemental calcium is A notable impairment of hemostasis arises with
replaced intravenously, it is important to continue to severe metabolic acidosis. Thus, in cases of severe
monitor serial arterial ionized calcium concentrations. hemorrhage, buffering toward physiologic pH values
Prolonged QT interval during MT may also be (arterial pH ! 7.2) is recommended, especially with
related to hypomagnesemia, and therefore both blood massive transfusion of older RBCs displaying
calcium and magnesium concentrations must be moni- exhausted RBC buffer systems.5 Patients with liver
tored during MT. Low levels of magnesium during failure who require massive transfusion may manifest
MT can be due to the infusion of large volumes of a metabolic acidosis that is more severe and difficult
magnesium-poor fluids as well as the binding of mag- to treat as they do not metabolize lactate, nor do they
nesium to citrate.43 convert the citrate in blood products to bicarbonate.
The impaired liver may also produce lactate, thus com-
Acidosis and Alkalosis pounding the problem.48
The storage of blood in citrate phosphate dextrose Blood Transfusion and Postinjury
adenine solution leads to a pH of 7.0 of most fresh Multiple Organ Failure
PRBC units. Blood pH decreases to 6.6 to 6.8 with
storage for 21 to 35 days, in part related to an Blood transfusion was first identified as an inde-
78
increased CO2 concentration.44 As citrate is metabo- pendent risk factor for multiple organ failure (MOF)
lized to bicarbonate, it is common that patients who in a 3-year single-institution study (n 5 394) aimed at
require MT frequently develop a metabolic alkalosis. finding a predictive model for postinjury MOF.49
Therefore the presence of a metabolic acidosis in Trauma patients (n 5 394) with an injury severity
25. Coagulation & Anesthesia. Dr Azam’s Notes in Anesthesiology 2013
COAGULATION SYSTEM AND PATHWAY ! !"#$%&'()'*+,,+-'

• The process of blood coagulation is of paramount
importance to survival. The blood clotting and subsequent !"'-/$3-*"'(( !"##$%&'(( )*++,&(-./"01"2#$+-*'(
dissolution of clot following repair of the injured tissue is
termed hemostasis.
4#$-&#&-+(( 53-*6$-*"'("7(3"$%,#$-*"'((
• Hemostasis has 4 major events
1. Vasoconstriction – This causes obliteration of vessel A""+&(2#$-&#&-($%%/&%$-&+((
)./"01*'(((
lumen caused by serotonin and vasoconstrictors from
platelets.
2. Platelet activation to form platelet plug 8*1/*'((((
3. Fibrin mesh formation due to coagulation pathway )&02"/$/D(.&0"+-$-*3(2#,%(((
9:8;<;):(=:>?@)5);!(
activation.
4ABC((
4. Clot dissolution by plasmin after tissue repair.
Platelet and Platelet activation: Platelet aggregation inhibition: PGE2, PGI2 and NO
• Vascular injury disrupts single layer of endothelial cells lining Coagulation cascade:
blood vessels exposing subendothelial proteins consisting of Essential features:
collagen, von Willebrand factor (vWf) and fibronectin. 1. Cascade system where precursor zymogen is converted to active
• These act as sites for attachment of platelets. Glycoprotein enzyme
1b on the surface of platelets makes adhesion of platelets to 2. Rapid response due to amplification of response.
vWf possible. 3. Limited in response in terms of location and duration due to
• Platelets are activated by collagen and thrombi. Activation of 1. Quiescent vascular endothelial cells
platelets causes release of arachidonic acid by 2. Negative feedback loops
Phospholipase A2. This is converted to thromboxane A2 3. Decrease in substrate
(TXA2) by Cyclooxygenase. Activated platelets also secrete Concentration by consumption
ADP, TXA2 and ADP also activate platelets. • Inhibition of coagulation enzymes after they are formed.
• These causes platelet to change shape to form long • Coagulation pathway (Fig.2) lead to fibrin clot formation through the
pseudopodia. Integrin α11β3 on the surface along with intrinsic pathway or extrinsic pathway. These finally converge into
pseudopodia fibrinogen and vWf links adjacent platelets common pathway.
together to form platelet plug.
Inhibition of platelet aggregation

• PGE2, PGI2 and Nitric oxide secreted by the vascular
endothelium inhibits platelet aggregation.
• Prevention of linking of platelets by internalization of α11 to
β3.
79

Coagulation & Anesthesia.Continuation:
Coagulation 1769 56
Intrinsic Pathway Extrinsic Pathway

Vascular endothelial
XII XIIa injury
XI XIa Tissue factor/

VIIIa VIIa complex
IX IXa
Section IV Anesthesia Management

X Xa “Prothrombinase complex”
Va
II IIa
XIII
Va/VIIIa XIIIa
Fibrinogen Fibrin monomer Cross-linked fibrin
Figure 56-1 Depiction of the classic coagulation cascade incorporating extrinsic and intrinsic pathways of coagulation. (From Slaughter TF: The coagulation
system and cardiac surgery. In Estafanous FG, Barash PG, Reves JG [eds]: Cardiac Anesthesia: Principles and Clinical Practice, 2nd ed. Philadelphia, Lippincott
Williams & Wilkins, 2001, p 320, with permission.)
Coagulation
plasma forminvolves different proteins
phospholipid-bound activation complexes
INTRINSIC inhibitor, tissue factor pathway inhibitor (TFPI).23 However, small
withPATHWAY:
tissue factor, factor X, and calcium to promote conversion
1. Zymogens of quantities
• It is so called because of all
thrombin generated protein
the necessary before neutralization
componentsofare the present in plasma. This can
21
factor X to Xa. Recently, the tissue factor/factor VIIa
2. Cofactors complex
occur withoutextrinsic
tissuepathway activate
injury (e.g. factor XIvessel
abnormal and thewall).
intrinsic pathway.
has
3. been demonstrated to activate factor IX of •the
Fibrinogen The intrinsic
first partThe
is intrinsic
called the pathway
contactsubsequently amplifies out
phase, carried and by
propagates
Factor the
XII, Prekallikrein and High
pathway, further
4. Transglutaminase demonstrating the key role of tissue factor in hemostatic response to maximize thrombin generation (Fig.
molecular weight kininogen (HMW Kininogen). Activation of factor XII to XIIa in vivo is by
initiating hemostasis.22 56-2). Although factor XII may be activated by foreign surfaces
exposed collagen and negatively charged phospholipids and in vitro by negatively charged
(i.e., cardiopulmonary bypass circuits or glass vials), the intrinsic
particles likepathway
kaolin,appears
glass,todextran sulphate,
play a minor role in etc.
initiation of hemostasis.
Intrinsic Pathway of Coagulation • Factor XIIa aProteins of the intrinsic pathwayfactor
serine protease, activates XI to XIa
may, however, and prekallikrein
contribute to to kallikrein.
Kallikrein in inflammatory
turn activates factor XII
processes, to XIIa. This
complement is called
activation, reciprocal activation.
fibrinolysis,
22,24
Classically, the intrinsic or contact activation system was
• described kinin generation, and angiogenesis.
Factor XIa activates factor IX to IXa which requires Ca2+, Factor IXA, Ca2+, X and factor
as a parallel pathway for thrombin generation by way of factor
VIIIa from a complex known as tenase complex, which converts factor X to Xa which forms
XII. However, the rarity of bleeding disorders resulting the entryfrompointCommon Pathwaypathway.
into common of Coagulation
Here factor VIIIa acts as a receptor for IX and X and is
contact activation factor deficiencies led to our current under-
called cofactor. The final pathway, common to both extrinsic and intrinsic coagu-
standing of the intrinsic pathway as an amplification system to lation cascades, depicts thrombin generation and subsequent
propagate thrombin generation initiated by the extrinsic pathway.22 fibrin formation. Signal amplification through both extrinsic and
Recent cell-based models of coagulation suggest that thrombin intrinsic pathways culminates in formation of prothrombinase
generation by way of the extrinsic pathway is limited by a natural complexes (phospholipid membrane bound activation complexes)
80
Dr Azam’s Notes in Anesthesiology

Blood 2013
Coagulation & Anesthesia.Continuation: Dr Azam’s Notes in Anesthesiology 2013
EXTRINSIC PATHWAY: Vitamin K dependent clotting factors:

• Initiation of fibrin clot formation in response to tissue injury is • They are factors, II, VII, IX, X. They are synthesized in the liver and
called extrinsic pathway. Tissue factor or factor VII is undergo post translational modification by γ carboxylation. This is
responsible for extrinsic pathway, so called because tissue carried out by vitamin K dependent γ glutamyl carboxylase. Coumarin
factor (TF) is not present in plasma, but supplied by vascular anticoagulants block this.
endothelial cells and leukocytes. After release of tissue factor Anti clotting mechanism:
it binds with factor VII which is then activated to TF-VIIa by Two ways:
thrombin, XIIa, IXa. TF – VII a complex converts factor X to 1. Limiting coagulation cascade
Xa. 2. Fibrinolytic system
FINAL COMMON PATHWAY: Control of coagulation cascade
• Factor Xa formed by extrinsic and intrinsic pathways activate It is by anti coagulant proteins. These include:
prothrombin to thrombin. This is prothrombinase complex i) Protein C
which consists of platelet surface complex which consists of ii) Protein S
platelet surface complex which consists of platelet surface iii) Antithrombin III
phospholipids, Ca2+, Factor Va factor Xa and prothrombin. iv) Thrombomodulin
Thrombin a serine protease converts fibrinogen to fibrin v) A2 macroglobulin
monomer. The fibrin monomers undergo polymerization vi) Heparin cofactor II
which leads to fibrin clot. Thrombin also converts factor XIII vii) Tissue factor pathway inhibitor
to XIIIa which cause cross linking of fibrin monomers to form • Antithrombin III (ATIII) is the important inhibitor of thrombin, factor IXa,
stable fibrin clot. Xa, XIa, XIIa. It is greatly augmented by heparin and heparin sulphate
• In the revised model of coagulation factor VIIa – TF complex present in vascular endothelium. AT III is called heparin cofactor.
is thought to initiate coagulation rather than contact phase. • Protein C (Fig. 3) together with thrombomodulin (TM) and protein S act
After an initial burst of Xa and thrombin, tissue factor as an important negative feedback loop. TM is a protein present on the
pathway inhibitor dampens VIIa/TF pathway. VIIa – TF also surface of quiescent vascular endothelial cells. TM binds with thrombin.
activates factor IX to IXa. So it is now thought that VIIa – TF This activates protein C. Activated protein C (APC) inactivates VIIIa and
complex is the principal initiator of coagulation, whereas in Va. Protein S potentiates protein C.
the intrinsic pathway is necessary to sustain coagulation ! !"#$%&'()) *) !"#$%&$%$+,-'())
response. This is because, no bleeding was observed in
contact factor deficiencies (factor XII, Prekallikrein, HMW
kininogen) but bleeding was observed in Factor XI deficient .#$/0'()1) ) ) 23/'45/0+)6#$/0'()1)))
patients.
78885)) ) 8(53/'40)78885)) 75)) ) 8(53/'40)75))
Regulation of protein C
81

• Heparin Cofactor II- This inhibits thrombin. It is potentiated 1. Zymogens of serine Activation Function
many fold by heparin. protease
• Tissue factor pathway inhibitor or lipoprotein associated Factor XII By binding to collagen, XIIa activates factor
coagulation inhibitor (LAC1) inhibits VIIA-TF. also to glass, kaolin, XI and prekallikrein
Fibrinolytic system: dextran.
• Degeneration of fibrin clot is a function of plasmin a serine Factor XI By XIIa Converts factor IX to IXa
protease that circulates as a proenzyme plasminogen. Need Ca2+
Conversion of plasminogen to plasmin by plasminogen Factor X Activated on surface of Activates prothrombin to
activator. activated platelets by thrombin
Plasminogen activation occurs through tenase complex or by TF-
1. Intrinsic system: Here plasminogen interacts with intrinsic VIIa in presence of Ca2+
pathway of blood coagulation to generate plasmin. Factor II Activated by Converts fibrinogen to
Accounts for 15% of fibrinolysis.
Prothrombinase complex fibrin
2. Extrinsic system: Consists of tissue type plasminogen
(Platelet phospholipids,
activator (t-PA) and urokinase type plasminogen activator
Ca2+, Va & Xa)
(u-PA). Endothelial cells release T-PA by the action of
Factor VII Activated by thrombin, Xa, Activates factors IX & x
thrombin, histamine, bradykinin, shear stress or
vasocclusion. VIIa and IXa
2. Co factors
! !"#$"%&'($)*+"(%&*%,&& Factor VIII Thrombin & Xa VIIIa is a cofactor for
& activating factor X by IXa
0.*/)"%(1-%&&
)-+*#(."/*+"(%& Factor V Thrombin & Xa Cofactor for the activation
23+$"%/"4&*4+"5*+"(%&6*+78*9&&&
=%+$"%/"4&*4+"5*+"(%& 23(1-%(</&*4+"5*+"(%& of Prothrombin by factor
6*+78*9&&&& 6*+78*9&&&& Xa
+:0;&&& <:0;&&& Factor III Cofactor for factor VIIa,
!*4+($&>=*&
D+$-6+(@"%*/-& Ca2+ dependant
!*4+($&>==*&
?*.."@$-"%&& 3. Fibrinogen
ABC&@"%"%(1-%&&&&& 0.*/)"%&&& Factor I Thrombin in presence of Forms Fibrin
!"#$"%&&,-1$*,*+"(%&4.(+&.9/"/&&& Ca2+
4. Transglutamase
0.*/)"%(1-%&*4+"5*+"(%&6*+78*9&&&&
Factor XIII Thrombin in presence of Stabilizes fibrin clot by
Ca2+ convalent cross links
Table 2: Functional classification of clotting factors.
82

NAME FUNCTION History:

Protein C Activated by thrombin bound to • History with regard to previous bleeding, petechiae, ecchymoses,
hemarthrosis, family history of bleeding disorders, drug history of use of
thrombomodulin, degrades VIIIa and Va
aspirin, non steroidal anti-inflammatory drugs, coumarin, heparin or
Protein S Cofactor for protein C
thrombolytic. History of uremia, liver disease, leukemia.
Thrombomodulin Protein on the surface of endothelial cells, • A recent uneventful tooth extraction or a minor surgery will virtually rule
binds thrombin which activates protein C. out the possibility of coagulation disorder in the patients.
vWf Present in plasma, subendothelial tissue and • If you get a positive history from a patient, then guidelines to your
endothelial cells. Carrier of factor VIII and approach are as given in Table 4. !
prolongs its half life, adhesive protein which Enquiry Action to be taken if response is positive
binds platelet to subendothelial tissue.
Past or recent history of Blood count, coagulation screen
HMW Kininogen Carries prekallikrein and factor XI and deliver
bleeding or bruising
them to anionic surfaces
Family history of Blood count, coagulation screen
Prekallikrein Activated by XIIa to Kallikrein which
bleeding
activates XII to XIIa
Drug history
Table 3: Regulatory and other proteins
Warfarin Discontinue 72h preoperatively. Use heparin if
ASSESSMENT OF COAGULATION FUNCTION AND necessary. In emergency reverse with FFP + vit
ANESTHETIC MANAGEMENT OF A PATIENT WITH Aspirin K
COAGULATION DISORDERS: Discontinue 72h preoperatively. Give platelets if
• Successful surgery depends, in part on adequate hemostatic Non-steroidal anti- bleeding excessive
ability of the patient. Haemorrhage and thrombosis are two inflammatory drug Discontinue 24h preoperatively. Watch for GI
major problems which affect the outcome of surgery. haemorrhage if anticoagulants used
Hemostasis depends on vascular integrity, platelet function postoperatively.
and coagulation. Assessment of coagulation function prior to Past history or family If positive or doubtful discuss thrombophilia
Surgery is of utmost importance for successful outcome of history of thrombosis screening with hematology laboratory. LMW
surgery. But doing all the tests of coagulation prior to surgery heparin should be used in all high risk
is not cost effective. So we have to approach every patient in situations.
a stepwise systematic manner and order appropriate tests Oestrogen containing Stop 4 weeks prior to elective surgery. For
whenever necessary. contraceptive pill emergency surgery use LMW heparin
• As with any patient, approach to a patient with possible prophylaxis.
coagulation disorder should start with a detailed history, as Hormone replacement Adhere scrupulously to normal prophylactic
many a time detection of potential problems in hemostasis therapy measures.
becomes evident in the history itself. Table 4 – Enquiries relevant to hemostasis to be made preoperatively
83

Test Normal Abnormalities Common causes

range indicated by of disorder
INR = ISI
prolongation
Thrombin time 14-16S Deficiency or Heparin therapy. • Where ISI is the international sensitivity index which is the calibration
(TT) abnormalities of DIC factor of the lab thromboplastin used for the test against a WHO
fibrinogen. reference preparation.
Inhibition of Integrity of intrinsic pathway:
thrombin by • Activated partial thromboplastin time (aPTT or PTT) measures the
heparin or EDPs integrity of the intrinsic pathway including factors VIII, IX, XI, XII as
Prothrombin 10-14S Deficiency or Warfarin therapy. well as V, X prothrombin and fibrinogen.
time (PT) inhibition of V, VII, Liver disease, Integrity of final common pathway:
X, prothrombin, Heparin, DIC, • It is measured by thrombin time. It is prolonged in functional
fibrinogen Vitamin K abnormality of fibrinogen and to inhibitors of thrombin activity including
deficiency the presence of fibrin degradation products.
Partial 30-40S Deficiency or Heparin therapy, Integrity of vascular endothelium, platelet function and number:
thromboplastin inhibition of V, VII, DIC, Hemophilia, • Measured by doing a bleeding time.
Thromboelastogram:
time with IX, X prothrombin, Christmas
fibrinogen disease, von • Even though this cannot be used as a screening test due to the costs
Kaolin (PTTK) involved, this gives a rapid complete assessment of all pathways, factor
Willebrandʼs
disease, liver abnormalities, platelet function and thrombolysis.
disease. • If you find an abnormality in the screening tests, individual factor
assays may indicate which factors are deficient and appropriate
Bleeding time 3-8 min Abnormal platelet Inherited disorders
replacement materials can be made available before surgery.
formation, of platelet function.
Reduced platelet Drug induced renal • Even though we know how to correct the coagulation abnormality, there
is no definitive answer as to when to correct the laboratory
number failure. Von
abnormalities in coagulation tests. The laboratory abnormalities should
Willebrandʼs
be corrected if there is potential risk of severe haemorrhage; keeping in
disease
mind that the blood products are expensive and can transmit diseases
Table 5: Screening test for coagulation disorders
and that transfusion to correct the coagulation abnormality may end up
in fluid overload.
Integrity of extrinsic pathway
• Prothrombin time (PT) measures the integrity of the extrinsic
pathway including factors VII, the common pathway factors
V, X, prothrombin and fibrinogen. It is expressed in terms of
international Normalized Ratio (INR) which is a method to
standardize the prothrombin time assay.
84

• Table 6 shows which coagulation factors are present in which Blood product Main coagulation Uses Comments
blood products and Fig.5 shows an outline to the approach factors
towards a patient with a possible bleeding disorder. Fresh frozen Fibrinogen, Correction of ABO compatible
plasma (FFP) prothrombin coagulation only should be given
Common conditions and guidelines to correct the coagulation factors, V, X, XI,disorders in liver (contains anti-A.B.
abnormalities. Some factor VIII, disease antibodies) stored at
1) Liver disease IX, VII Replacement of < - 300C Potential
factors in DIC or source of HIV,
• In liver disease with coagulation abnormalities, there will be
following major hepatitis viruses
prolongation of the prothrombin time. The consensus now (to
trauma should be used
correct the coagulation abnormality) is that if platelet count is Replacement within 30 min of
greater than 80 x 109/L (80,000/-mm3), and bleeding time is during massive rapid thawing
normal, administration of fresh frozen plasma (FFP) is transfusion
unnecessary if the INR is < 1.6. These patients can be Cryoprecipitate Fibrinogen Additional source No ABO antibodies
managed by giving 10mg Vit. K IM daily x 3 days and (50-80g/dl) of fibrinogen and present
availability of FFP should be ensured in the per operative Factor VIII (2-5u/ factor VIII in Single donor but
period. ml) massively potential source of
• If the INR is greater than 1.8 or if there is thrombocytopenia transfused patients. virus transmission.
or platelet dysfunction, FFP or cryoprecipitate should be Source of factor Useful addition to
given within 6 hours of the start of surgery. VIII for mild FFP if volume
hemophiliacs or overload is a
heterozygotes at problem
risk Stored at -200C
To correct bleeding Stable for 6 months
time and permit
surgery in patients
with platelet
storage disease
Albumin solution No coagulation Volume Small risk of virus
factors replacement transfusion
Platelet Platelets In disorders of ABO compatible
concentrates platelet production. should be used can
In platelet storage transmit viruses
disease including CMV
In massively (unless white cell
transfused patients depleted)
Not effective in
immune
thrombocytopenia.
85
Table-6: Blood products used for hemostasis
Read Patient with possible bleeding disorder - Chart from old • For conditions due to increased destruction of platelets – like in immune
notes: thrombocytopenic purpura (ITP), intravenous immunoglobulin and
2) Patients on anticoagulants steroids should be given to raise the platelet count.
• Oral anticoagulants should be stopped at least 72 hours • Exposure to antiplatelets drugs will increase the risk of surgical
preoperatively and maintained on heparin during the haemorrhage whatever the route of anesthesia. Aspirin should ideally
perioperative period especially if the oral anticoagulants were be stopped one week before surgery and definitely 72 hours prior to
started for prosthetic cardiac values or for recent surgery and non steroidal and inflammatory drugs two days prior to
thromboembolism. Ideally the therapeutic dose of heparin is surgery. If for emergency surgery, if aspirin cannot be stopped, bleeding
adjusted to maintain aPTT at about double the normal value can be controlled by transfusing platelet rich plasma.
of 25 to 30 seconds. Disorders of Hypercoagulability:
3) Hemophilia • Patients who undergo prolonged abdominal surgery or surgery to the
• For major surgery, in a patient with hemophilia A, a target legs particularly if they require a period of reduced mobility
concentration of 100% factor VIII is set, to be maintained for postoperatively are at a high risk from venous thrombosis and
the first 5-7 postoperative day, whereas minor procedures embolism. The risk is increased if they have one or more risk factor
may be adequately covered by concentration of 50% after given in table 7. These patients require anticoagulant measures during
the first day. and / or after surgery with subcutaneous heparin.
• For hemophilia B, factor IX concentrate is given to maintain a Related to venous stasis Thrombophilic states
plasma concentration of 30% of normal during the
• Immobility • Hereditary
perioperative period.
• Dehydration • Ant. Thrombin III,
4) Platelet disorders
• Cardiac failure • Protein C deficiency
• Patients with platelet counts above 50 x 104/L (50,000/mm3)
• Stroke • Protein S deficiency
do not need prophylactic platelets. If it is less than 50 x 109/
• Pelvic obstruction • Acquired
L, prophylactic platelets may be advisable, particularly if the
• Nephrotic syndrome • Lupus anticoagulant
patient requires transfusion of red cells intraoperatively – as
• Varicose veins • Paroxysmal nocturnal
transfusion of red blood cells lowers the platelet count
• Hyper viscosity hemoglobinuria
probably by increasing the consumption of platelets through
• Sickle cell disease • Pregnancy and Puerperium
complement activation. If platelet count < 30 x 109/L (30,000/
• Multifactorial • Estrogens
mm3), then it is advisable to raise the count to 30x109/L pre
• Age • Hormone replacement therapy (?)
surgery and then to give platelets in theatre according to
• Obesity • Surgery-abdominal and hip
bleeding tendency and to maintain the count above 30 x 109/
• Sepsis • Malignant disease
L pre surgery and then to give platelets in theatre according
• Major trauma
to bleeding tendency and to maintain the count above 30 Table-7 Risk factors of Thromboembolism
x109 L in the postoperative period.
86

Points to remember before giving anesthesia Property Unfractionated Low molecular

• I/M medication are best avoided whenever possible. heparin weight heparin
• Choice of regional anesthesia especially central neuraxial Mean molecular weight 15 KDa 4.5KDa
blockade is avoided in patients with coagulation failure.
Anti XA / Anti IIa activity 1:1 3:1
• In general anesthesia, nasal intubation is avoided.
• Drugs like Warfarin are highly protein bound drugs and can Inhibition of platelet function Yes No
displace protein bound anesthetic drugs. Bioavailability in low dose 50% 100%
• Patients may have coexisting liver disease and drug Elimination Hepatic and Renal Renal
metabolism would be affected.
• These patients may have received previous blood t1/2 of anti Xa activity
transfusion and so universal precautions should have to be Intravenous 1hr 2hrs
taken to avoid transmission of HIV and Hepatitis B. Subcutaneous 2 hrs 4hrs
With this knowledge, a patient with coagulation abnormality Thrombocytopenia High Low
can be efficiently managed during the peri operative period. Risk of hemorrhage + Decreased
Osteoporosis with prolonged Yes Yes
ANTICOAGULANTS AND REGIONAL ANESTHESIA: therapy
• Increasing number of patients now receive oral anticoagulant Neutralization with protamine Full Anti lla fully
therapy to reduce the risk of stroke from atrial fibrillation and neutralized. Anti Xa
other cardiac disorders. It is generally accepted that some partial.
regional anesthetic techniques will be hazardous in the Table 8: Comparisons of properties of Unfractionated and low molecular
presence of coagulopathies and anticoagulants. In particular weight heparin
during central neuraxial blockade (intrathecal, extradural,
caudal anesthesia), bleeding is contained in a space Anticoagulants commonly used are:
restricted by bone. Heparin
• Un-fractionated heparin
Anticoagulants are used for • Low molecular weight heparin
1. Established venous thromboembolism Coumarins
2. Prophylaxis against deep vein thrombosis. Aspirin
3. Patients with prosthetic heart valves
4. To prevent extension of an arterial thrombus
5. As a long term anticoagulation to prevent arterial thrombo-
embolism in patients with large left atrium or atrial
fibrillation.
6. Antiplatelets therapy to reduce the incidence of fatal and
non-fatal myocardial infraction in patients with unstable
angina.
87

HEPARIN: • In presence of blood during needle or catheter placement, heparin

• Unfractionated heparin and low molecular weight heparins therapy is delayed for 24 hours.
are commonly used. Their properties are given in Table 8. • Single shot spinal anesthesia carries the least risk in central neuraxial
• Heparin is now used increasingly to blockade.
- Reduce the risk of deep vein thrombosis • If the patient is on a standard dose regimen of heparin, anesthesia
- Reduce the risk of venous thromboembolism. must be delayed for 12 hours following last dose if possible.
• In orthopedic surgery, without prophylaxis, deep vein • If on a high dose anesthesia is delayed for > 24 hours.
thrombosis occur in 50-70% of patients undergoing total hip
replacement, total knee replacement, or hip fractures. DICOUMAROLS
Regional anesthesia and heparin: • Dicoumarol are Vitamin-K antagonists and inhibit the formation of
• Spinal bleeding following epidural catheters occurs in factors II, VII, IX and X. Dicoumarol are stopped about 3-5 days before
approximately 1:200,000 cases, more common in elderly surgery and converted to heparin.
women (75%) • Prothrombin time (PT) is monitored for dicoumarol activity, and
• Removal of epidural catheter is a significant risk factor of activated partial thromboplastin time (aPTT) is monitored for activity of
spinal bleeding. 30-60% of clinically important hematomas heparin.
occurs in this circumstance. • When PT is less than 1.5 times the normal and aPTT is about 55-70
RECOMMENDATIONS: sec. it is considered to be effective weaning from dicoumarol and
• Smallest possible needle used for regional anesthesia. effective anticoagulation by heparin.
• Smallest effective dose of aspirin used preoperatively Regional anesthesia and dicoumarol:
• Low molecular weight heparins should be delayed as long as • As all patients on dicoumarol are converted to heparin preoperatively,
possible postoperatively, in case of neuraxial anesthesia (12 all the recommendations for heparin holds true for patients on
hours minimum, preferably 24 hours). dicoumarol too.
• For central blockade, avoid preoperative administration. • Postoperatively dicoumarol are started but, before starting dicoumarol,
• First dose of subcutaneous heparin is administered after or before the drug gets effective, catheter introduced epidurally has to
establishment of block be removed.
• In post operative period, catheter removal should take place ASPIRIN AND OTHER NON STERIODAL ANTI INFLAMMATORY DRUGS
in a period 1 hour before dose of heparin is administered to (NSAIDS)
just before the administration of next dose i.e., when • Low dose aspirin therapy about 75mg daily is given for most patients
anticoagulant activity is at the lowest. with coronary artery disease to decrease the risk of platelet aggregation
• One dose may be stopped after removal of catheter. and embolism.
• Frequent evaluation of neurological status is done. If
continuous infusions are used for postoperative analgesia,
dilute solutions will be preferable as with them the motor
block will be low and may not affect the neurological
examination.
88

• Aspirin irreversibly acetylates platelet cyclooxygenase, the Manifestations of complications of regional anesthesia in anti coagulated
enzyme that converts arachidonic acid into prostaglandin patients
endo-peroxidases, which is needed for platelet aggregation. • Hematoma formation and nerve compression are common
• Because cyclooxygenase is not regenerated in circulation complications, which occur in these patients.
within the life span of platelet, one aspirin affects platelet • In central neuraxial blockade, hematoma is restricted by spinal canal
function for a week. and permanent damage to spinal cord or nerves occurs.
• Warning signs include localized back pain and signs of nerve
• Other NSAIDS and drugs that inhibit platelet function e.g. Vit compression. These signs may be masked by blockade, especially if
E, sulphinpyrazone, dipyridamole, antidepressants, the technique is used in postoperative analgesia
phenothiazines, furosemide, steroids etc, inhibit platelet
function reversibly and for about 24-48 hours.
• If emergency surgery is needed, before 8 day period of
stopping aspirin or 2 day period of stopping other drugs
mentioned other than aspirin, 2-5 units/70Kg of platelet
concentrate will bring platelet concentration to a normal. This
may also reduce the risk of hematoma formation after
regional anesthesia.
• Low dose aspirin < 650 mg/day allows aspirin to be gone
from the body 24 hours after administration of the last dose.
Because the body makes about 70,000 platelets /ml/day, a
48 hour period is sufficient for platelet aggregation to
become normal and regional anesthesia becomes safe.
• Considerable controversy exists in the area of stopping
aspirin before anesthesia. Bedside platelet function test (Ivy
bleeding time) may provide guidance as to safety, should be
< 10 minutes. According to some workers, there are practical
difficulties with standardizing and reproducibility of test and
wide normal range
89

26. Hemophilia. Dr Azam’s Notes in Anesthesiology 2013
Bleeding Disorders: Preoperative evaluation and preparation

Hereditary Acquired • Ask history of unusual bleeding
• History of hemostatic responses to prior operations (tonsillectomy,
Hemophilia A,B DIC
dental extractions)
Von willebrands Perioperative anticoagulation • History of drug ingestion (aspirin, oral anticoagulants)
disease • On physical examination petechial which suggests thrombocytopenia/
Afibrinogenemias Dilutional thrombocytopenia abnormal platelet function/defects in vascular integrity
• Coagulation tests to be done: BT, CT, PT, APTT, platelet count
Factor V deficiency Massive blood transfusion thromboelastography, thrombin time.
Protein C Deficiency Drug induced hemorrhage/platelet • History of coexisting diseases (hepatic, renal) or scheduled surgery
(CPB, liver transplantation) which may alter coagulation.
dysfunction
Antithrombin III ITP, TTP
Premedication:
deficiency Ideally given orally
•
Vitamin K deficiency Im injections avoided
•
Type of surgery (CPB) • Anticholinergic given iv if necessary
Clinical Features of hemophilia • Correct the factor level up to normal or 100% using desmopressin
0.3µg/kg iv
• Easy bruising, prolonged bleeding after trauma/surgery
• Factor VIII concentrates and infusion of 1U/kg which increases plasma
• Bleeding into joints and skeletal muscle hemorrhages factor VIII level by 0.02U/ml
• Bleeding into closed spaces can result in compression of • 0.3U/ml factor level gives minimal hemostasis.
peripheral nerves or vascular or airway obstruction. • 0.5U/ml factor level necessary for serious bleeding disorder.
• Intracranial bleed may lead to death
Diagnosis: Hemophilia and Coagulation Disorders:
• History of unusual bleeding Classification:
• Laboratory test • Hemophilia: Type ʻAʼ (X linked recessive disorder) (85%) 1:5000
- Normal platelet count and PT incidence à Factor VII deficiency
- Prolonged activated PTT • Hemophilia: Type ʻBʼ (14%) (X linked recessive pattern) à
- Specifically factor VIII/IX/XI deficiency deficient or defective factor IX
• Hemophilia: Type ʻCʼ (1%) (autosomal disorder) à deficiency in
factor XI
90

Hemophilia.Continuation: Dr Azam’s Notes in Anesthesiology 2013
• Coagulant factor VIII is a plasma protein that has two • Localization of coagulation and control of primary hemostasis are
components, factor VIII; VWF and factor VIII: C each of controlled by factor thrombosis A2, PG and prostacyclins.
which is under separate genetic control. • TxA2 released at the site of injury and stimulates vasoconstriction ADP
• VWF components serves to adhere platelets to collagen in release and platelet aggregation.
the sub-endothelial lower of blood vessels during primary • Prostacyclin is produced by intact endothelial cells and prevents
hemostasis and to carry the factor VIII molecule. platelet aggregation and clot formation.
• In hemophilia A this factor VIII: C is deficient in quantity or • Clot localization is maintained by dilution of procoagulants flowing in the
quality. blood the removal of activated factors by the liver the action f circulating
• Physiologic events after endothelial interruption in the blood procoagulant inhibitors such as antithrombin III and protein C and
vessel. The small size of platelets relative to other blood release of serine protease tissue plasminogen activator (TPA). TPA
components results in slower transit in the blood vessel with digests fibrinogen as well as factors V and VIII, initiating the physiologic
resultant margination the process in which the faster mving, process of fibrinolysis and resulting in fibrin degradation (split) products,
larger components push the platelets toward the walls of the which are removed by the mononuclear phagocyte system.
blood vessel. As a result platelets are in contact with the
surface of the blood vessel and can immediately detect any Extrinsic Coagulation Pathway:
break in endothelium. Any endothelial break exposes ! $/--34! 6'(('0!*,.%7,8-!'9!
platelets to subendothelial structures including collagens and
.&,3(,! :',;3+,./'0!!
other activating proteins, which cause the glycoprotein <&'.%&'()/0!1""2!!
$%&'()'*+,-./0!1"""2!#""!!!!"#!
! !
receptors on the platelets to rapidly adhere to these
substances. This adhesion begins the process of platelet ! !
"#!
activation, in which the shape of the platelet is changed and 5! =/)&/0';40!
! !
#! !
the contents of the cytoplasmic granule are released. These #"""! ! "#!
substances include factors such as ADP, which further ! $%&'()/0!
stimulate platelet aggregation. The platelet plug that is 5"""!!!5"!!!"5! ! "#!
1"#2!! !
formed in this process provides initial hemostasis. ! !
! >'+3)+4!9/)&/0!
• Activation of factor XIII produces cross polymerization of !
loose fibrin to produce firm clot. "#!
5"""!
6'++,;40!! !
!
! =/)&/0!:+'.!!
"0.&/0-/:!6',;3+,./'0!*,.%7,8! !
!
91

The levels of factor VIII necessary for hemostasis: • ACT also is an accelerated version of PTT and activated by
Clinical Presentations Factor eight concentrations diatomaceous earth, but less sensitive than aPTT to specific factor
deficiencies.
(%) of normal
• Thrombin time measures conversion of fibrinogen to fibrin, a useful test
Spontaneous hemorrhage 1 – 3% to determine both inadequate amounts of fibrinogen as well as
Moderate trauma 4 – 8% inadequate fibrinogen molecules.
Hemarthrosis and deep 10 – 15% • Thrombodiastogram measures both speed of clot formation as well as
clot firmness and helpful following transfusion of large quantities of
skeletal muscle hemorrhage blood products.
Major surgery > 30%
Preoperative evaluation and preparation:
Specific components measured by different coagulation tests:
1. Correct the patients coagulation status before surgery.
Laboratory tests Normal values Components
measured • Factor VIII levels of 30% of normal will usually provide adequate
Bleeding time hemostasis. For a major orthopedic procedure, the level should be
3 – 10 minutes Platelet count, corrected to 100% of normal approximately 1 to 2 hours before
vascular integrity procedure. A repeat dose should be given if surgical procedure lasts
Prothrombin time 10 – 12 seconds I, II, V, VII & X more than 1.5 hours or if measured factor VIII levels falls below 40% of
Partial 25 – 35 seconds I, II, V, VII, IX, X, normal.
Thromboplastin time
XI, & XII • One unit of factor VIII: C clotting activity is defined as the amount
(PTT) present in 1ml of fresh normal, pooled plasma.
Thrombin time 9 – 10 seconds I, II • A single unit of factor VIII clotting activity per kilogram of baby weight
ACT 90 – 120 seconds I, II, V, VII, IX, X, will increase plasma factor VIII levels approximately 2%.
• Factor VIII concentrates are very stable at room temperature after
XI & XII reconstitution and thus are appropriate for infusion use.
• PT is measured by adding tissue from thromboplastin (TP) to • But approximately 10-20% of hemophilics will develop an antibody
a blood specimen and measuring the time until clot inhibitor against factor VIII and do not achieve the anticipated response
formation. A normal PT could occur with an abnormal following factor VIII infusion. But some patients who do not respond
fibrinogen level. Because the PT is only prolonged if the well to bolus injections, a continuous infusion can be effective because
fibrinogen level <100mg/dl. appropriate level of missing factor can be achieved relatively easily by
• PTT is performed when partial thromboplastin is added to a infusion, because complete inhibition of factor only occurs after 1-2
test tube of blood and time is measured until clot forms. This hours. If the factor is continuously infused, there will always be some
test can be modified by the addition of the surface activating that is circulating, unneutralized and hemostatically active.
factors XII and XI before the addition of the partial
thromboplastin, creating the activated partial thromboplastin
time (aPTT). The aPTT is a faster test than PTT and is a
standard test used in clinical practice .
92

2. Factor VIII activity is present in FFP and cryoprecipitate: • In addition factor VIII: C and vWF are released from endothelial cells.
FFP: • The half time of this released factor is approximately 12 hours and
• Prepared from single donor repeated administration of DDAVP will deplete the storage capacity in
• Contains all plasma proteins and factor VIII the endothelial cells.
• After blood donation, approximately 200ml of FFP are • If DDAVP is to be used preoperatively the release of plasminogen
extracted. activator by DDAVP mandates the use of EACA as well which is a
• Factor VIII activity is between 0.7 – 0.9 units of clotting antifibrinolytic.
activity per ml of FFP.
• FFP may carry AIDS and hepatitis B, C etc., Advantages of Factor III :
Advantages Disadvantages
Indications for FFP
Cryoprecipitate • Readily available Allergic reaction
• Isolated factor deficiency
Volume expands/massive blood transfusion • Long shelf life Hyperfibrinogenmias
•
Reversal of antithrombin III deficiency • Low risk of AIDS and
•
hepatitis
• Selected immune deficiencies
Factor VIII concentrates • Easily stored and High risk of infection
• Thrombocytopenic purpura
reconstituted long life,
Cryoprecipitate: known potency
• It is fraction of plasma that precipitates when FFP is thawed. Monoclonal purified • Stability, biologic Cost (?)
• It contains ! safety
factor VII
- Factor VIII: vWF
- Factor XIII, fibrinogen
• 5-12 units of factor VIII clotting activity/ml
Indications:
• Hemophilia, VWF disease, hypofibrinogenemia uremic
platelet dysfunction
• It may sensitize the Rh –ve individuals to Rh antigens if the
donor is Rh +ve because of presence of small amounts of
red cell frequents in cryoprecipitate.
• Synthetic analog of ADH is used to prepare mild and
moderate hemophilias for minor surgery.
• Intravenous DDAVP will rapidly release preformed. Factor
VIII complex, which leads to a two to threefold increase in
circulating factor VIII within 30-60 minutes of administration.
93

Intraoperative Management: • If there is blood loss during surgery, whole fresh blood should be
1. Iron injections can be safely administered if factor VIII preferably transfused because it increased O2 carrying capacity and
activity is greater than 30% provides all components of coagulation and also expands the
2. Sedatives or anticholinergic drug should be given iv routes intravascular volume.
3. Regional anesthesia is contraindicated because of concern • If there is acute hemolytic transfusion reaction occurs during intra
of hematoma formation at the regional site. But with proper operative during blood transfusion, immediately stop transfusion and
management of the coagulation status, regional techniques draw blood from the patient and send to blood bank for further cross
can be used successfully. matching. An additional tube of blood should be collected and allowed
• But in a patient with full stomach, regional technique might to sit undisturbed for 5-10 minutes allowing separation of red cells from
be more appropriate because relative risk of aspiration plasma. The presence of free plasma Hb in the serum is diagnostic of a
• For a completely elective procedure in hemophiliac patient hemolytic reaction.
GA is better. • If life threatening hemorrhage occurs and patient is having high titre of
• Manipulation of airway during intubation should not be antibodies (IgG) against factor VIII, then massive doses of factor VIII
performed until appropriate replacement factors have been concentrates and plasma pheresis with replacement of factor VIII
administered. should be given and it may be of temporary benefit.
• Elective laryngoscopy should only be attempted following • Porcine factor VIII may provide hemostasis because of its distinct
preoperative factor correction and achievement of complete antigenecity even in presence of circulating inhibitors.
muscle relaxation. • Alternatively APC activated prothrombin complex concentrates which
• A smaller than predicted small well lubricated ETT well contain vitamin K dependent enzymes as well as recombined factor
lubricated ET Tube to be used for intubation. VIIIa can be given. These activated coagulants enter coagulation
• Avoid nasal intubation because of increased chance of cascade distal to level of factor VIII and bypass the effects of inhibitor
epistaxis. thrombosis is a possible complication.
• Carefully face mask is applied to avoid trauma to lips, tongue • During extubation gentle oropharyngeal suction to be done under direct
or face. vision.
• Strict asepsis to be maintained.
• Gentle face mask application and ventilation. Post operative Management:
• Coexisting liver diseases is a common complication in 1. Analgesics, containing aspirin/NSAIDs avoided
hemophiliac patients because of hepatitis acquired from 2. Antihistamines and antitussives can be inhibit platelet aggregation
previous blood or factor transfusion. So, drugs which are and prolong bleeding time. So to be used continuously.
metabolized by liver should be used with caution. 3. Narcotics paracetamol in titrated dose can be used for pain
• A balanced intravenous technique is preferable to an inhaled 4. If regional blockade with catheter was used for anesthesia, analgesics
anaesthetics because of reduced hepatic blood flow can be given through this route.
observed in inhaled technique. Halothane is avoided. 5. Factor VIII are supplemented for at least 2 – 4 weeks following
surgery.
6. Postoperatively some surgeries maintain factor VIII level at 80% of
normal for first 4 post operative days, whereas others feel that levels
at least 40% of normal are adequate. 94
7. Home infusions of factor VIII concentrates can also be used.
Correction of factor VIII level:

Single unit of factor VIII clotting activity per kilogram of body
weight will increase plasma factor VIII level s approximately
2%.
E.g., to correct a 70kg hemophilia patient with 5% factor VIII
activity to 95% of normal will be
95

27. Coagulation Factors. Dr Azam’s Notes in Anesthesiology 2013
Table 24.1 The coagulation factors.
Factor number Descriptive name Active form

I Fibrinogen Fibrin subunit
II Prothrombin Serine protease
III Tissue factor Receptor/cofactor*
V Labile factor Cofactor
VII Proconvertin Serine protease
VIII Antihaemophilic factor Cofactor
IX Christmas factor Serine protease
X Stuart–Prower factor Serine protease
XI Plasma thromboplastin antecedent Serine protease
XII Hageman (contact) factor Serine protease
XIII Fibrin-stabilizing factor Transglutaminase
Prekallikrein (Fletcher factor) Serine protease
HMWK (Fitzgerald factor) Cofactor*
HMWK, high molecular weight kininogen.

* Active without proteolytic modification.
Table 24.2 The coagulation factors.
Factor Plasma half-life (h) Plasma concentration (mg/L) Comments
}
II 65 100 Prothrombin group: vitamin
K needed for synthesis;
VII 5 0.5
require Ca2+ for activation
IX 25 5
X 40 10
}
I 90 3000 Thrombin interacts with 96
them; increase in
V 15 10
inflammation, pregnancy,
VIII 10 0.1 oral contraceptives
28. Artificial BloodBlood Substitutes Dr Azam’s Notes in Anesthesiology 2013
ARTIFICIAL BLOOD CELLS DISADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS

• Artificial blood or blood surrogates is a substance used to mimic • Often causes flu-like symptoms.
and fulfill some functions of biological blood, usually in the • This is often caused by phagocytosis of the perfluorocarbons emulsion by
oxygen-carrying sense. the recipient organism's immune system.
• The main aim is to provide an alternative to blood transfusion. • Unable to remain mixed as aqueous solutions – thus, they must be prepared
• Artificial blood does not contain the plasma, red and white cells, as emulsions for use in patients.
or platelets of human blood, but functions to transport and • A decrease in blood platelet count.
deliver oxygen to the body's tissues until the recipient's bone • PFC products cannot be used by the human body, and must be discarded.
marrow has regenerated the missing red blood cells. This takes approximately 18-24 months.
• Artificial blood can be produced in different ways using synthetic • PFCs absorb oxygen passively, patients must breathe at a linear rate to
production, chemical isolation, or recombinant biochemical ensure oxygenation of tissues.
technology.
• Current blood substitutes are either haemoglobin-based oxygen ADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS (HBOCS)-
carriers (HBOCs) or perfluorocarbons (PFCs). • Available in much larger quantities.
• While HBOCs utilize haemoglobin, an actual component of red • Can be stored for long durations.
blood cells, PFCs rely solely on synthetic chemical processes. • Can be administered rapidly without typing or cross-matching blood types.
Can be sterilized via pasteurization.
COMPOSITION OF ARTIFICIAL BLOOD
• Perfluoro-octyl bromide - 28% DISADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS
• FO-9982 - 12% (HBOCS)-
• Yolk lecithin - 2.4% • Reduced circulation half-life
• DSPE- - 0.12% • Disrupts certain physiological structures, especially the gastrointestinal tract
• Distilled water - 57.48% and normal red blood cell haemoglobin.
• They release free radicals into the body.
ADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS
• PFCs do not react with oxygen. IDEAL CHARACTERISTICS OF ARTIFICIAL BLOOD
• PFCs allow easy transportation of the oxygen to the body. 1. Safe to use.
• They allow increased solubility of oxygen in plasma. 2. Compatible in human body.
• PFCs minimize the effects of factors like pH and temperature in 3. Able to transport and release oxygen where needed.
blood circulation. 4. Storable and durable for longer time periods.
5. Is free of pathogens and toxins which would produce an immune system
response in the human body.
97

Artificial BloodBlood Substitutes Dr Azam’s Notes in Anesthesiology 2013
• Perfluorocarbons (PFC) based- Perfluorochemicals cannot mix

with blood, therefore emulsions must be made by dispersing
small drops of PFC in water.
• This liquid is then mixed with antibiotics, vitamins, nutrients and
salts, producing a mixture that contains about 80 different
components, and performs many of the vital functions of natural
blood.
Artificial blood Blood substitute
• The main purpose of artificial • The main purpose of a blood

blood is to act as normal substitute is to provide
blood in the body, providing temporary support to the
a long-term solution to blood circulatory system when
loss or distortion. No working necessary.
artificial blood has been • Blood substitutes generally
created in the status quo. are focused on the role of
transporting oxygen for
short-term cases such as
blood transfusions or
surgeries.
• Blood substitutes are
generally simpler since they
are only focused on one of
the several functions of real
blood. Several types of
blood substitutes have been
found including:
• Hemoglobin-based oxygen
carriers Perfluorocarbons
emulsion
98

29. What is recombinant factor VIIa? Describe the clinical usage of it? Dr Azam’s Notes in Anesthesiology 2013
• Recombinant human coagulation Factor VIIa (rFVIIa), A summary of the structure and properties of coagulation factor VII is as follows:
intended for promoting hemostasis by activating the I. Synthesis and localization - Synthesized in the liver and circulates in the
extrinsic pathway of the coagulation cascade. plasma as a zymogen
• Factor VII (formerly known as proconvertin) is one of II. Half-life - 3-6 hours
the proteins that causes blood to clot in the coagulation III. Molecular weight - 50,000
cascade. It is an enzyme of the serine protease class. A IV. Structure - Amino-terminal (light chain), carboxy-terminal (heavy chain)
recombinant form of human factor VIIa . catalytic domain, 2 epidermal growth factor domains
• Administration approval for uncontrolled bleeding in V. Cofactor - Tissue factor
hemophilia patients. VI. Substrate - Factor VIIa/tissue factor complex activates factors X and IX
• It is often used unlicensed in severe uncontrollable
bleeding. • Replacement therapy for persons with factor VII deficiency depends on the site
and severity of bleeding and the baseline factor VII activity.
Physiology:
• Spontaneous hemorrhage or mild trauma, therapeutic factor VII levels of 5-10%
• The main role of factor VII (FVII) is to initiate the process are sufficient to stop bleeding.
of coagulation in conjunction with tissue factor (TF/factor • This level may be achieved by administering plasma at a dose of 5-10 mL/kg of
III). body weight and repeating the dose every 8-12 hours for 1-2 days or major
• Tissue factor is found on the outside of blood vessels - hemorrhage or surgery, plasma may be administered in a loading dose of 15-20
normally not exposed to the bloodstream. Upon vessel mL/kg and followed by 3-6 mL/kg every 8-12 hours until the surgical wound
injury, tissue factor is exposed to the blood and heals.
circulating factor VII. • This may require 5-7 days of treatment.
• Once bound to TF, FVII is activated to FVIIa by different Dose: 20 - 90 µg/Kg
proteases, among which are thrombin (factor IIa), factor
Xa, IXa, XIIa, and the FVIIa-TF complex itself. FDA Approved Indications of Factor VII A:
• The most important substrates for FVIIa-TF are Factor X • Hemophilia A/B with inhibitors - 90 µg/kg every 2 hours
and Factor IX.
• Congenital factor VII deficiency - 15 0 30 µg/kg every 4 to 6 hours.
• The action of the factor is impeded by tissue factor • Acute Hemophilia - 70 - 90 µg/kg every 2 - 8 hours
pathway inhibitor (TFPI), which is released almost
immediately after initiation of coagulation. RCTʼS:
• Factor VII is vitamin K dependent; it is produced in the • Body trauma - 200 µg/kg then 100 µg/kg BD
liver. Brain Trauma 40 - 100 µg/kg
•
• Use of warfarin or similar anticoagulants decreases • CVS surgery - 50 - 160 µg/kg
hepatic synthesis of FVII. ICh - 15 - 160 µg/kg
•
• Liver transplant 100 - 200 µg/kg
99

100

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Dr.

To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for

Dr Azam’s Notes in Anesthesiology 2013

A NOTE TO THE READER

Dr Azam’s Notes in Anesthesiology 2013

1. Blood & Blood Products - 6 25. Coagulation & Anesthesia - 79

Dr Azam’s Notes in Anesthesiology 2013

History: • Only in pathological situations significant hematopoietic activity occur in

Dr Azam’s Notes in Anesthesiology 2013

White Cells: Blood Volume:

Dr Azam’s Notes in Anesthesiology 2013

Blood group systems: Storage of Blood:

Dr Azam’s Notes in Anesthesiology 2013

CPD (citrate phosphate dextrose) 6) Frozen storage:

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

COMPATIBILITY TESTING: b) Incubation phase:

Dr Azam’s Notes in Anesthesiology 2013

="2)0"'-E(&#"-#&(F#"2)0"'$2)#&(( Bombay Blood group:

Dr Azam’s Notes in Anesthesiology 2013

There are two Systems: ABO & Rh.

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

BLOOD TRANSFUSION: Recommendations:

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

iii) Washed red cells: II. Leukocytes:

Dr Azam’s Notes in Anesthesiology 2013

ii) Single donor platelets: IV. PLASMA FRACTIONS:

Dose of FFP: 1 unit for every 10 kg.

Dr Azam’s Notes in Anesthesiology 2013

2) Cryoprecipitate: Replacement therapy for coagulation factor deficiency:

Dr Azam’s Notes in Anesthesiology 2013

VII. Antithrombin III concentrates: Blood substitutes:

Dr Azam’s Notes in Anesthesiology 2013

ii) Polyfluoro-octobromide (Perflubron):

Dr Azam’s Notes in Anesthesiology 2013

Complications of Massive Blood transfusion:

Dr Azam’s Notes in Anesthesiology 2013

• Clotting abnormalities (after • Citrate toxicity:↓ in

A massive transfusion of red blood

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

• Guidelines based on literature, case studies, and consensus statements .

Regional anesthesia in a patient on anticoagulants - ASRA

Dr Azam’s Notes in Anesthesiology 2013

• Anti-thrombotic effect through factor Xa

Dr Azam’s Notes in Anesthesiology 2013

Disseminated intravascular coagulation (DIC), also known as disseminated intravascular coagulopathy

Thrombosis Clotting factor Bleeding

RBCʼs Tissue Ischemia Fibrinolysis Decreased

Fibrin degradation products (inhibit

Dr Azam’s Notes in Anesthesiology 2013

Infection: Obstetric: Malignancy: Traumatic: Intravascular Hemolysis:

Treatment & Management of DIC: Peri-operative Anesthetic implications & Management:

Dr Azam’s Notes in Anesthesiology 2013

A. Packed Red Cells: FFPʼs Continued:

!"#$"%&'(%)"#$"%+#"$(%)) ,-./0.12-.)) ,5%#"%&'(%)56$(5))