Volume 60, Number 12

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright © 2005
by Lippincott Williams & Wilkins CME REVIEWARTICLE 36
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total
of 36 AMA/PRA category 1 credit hours can be earned in 2005. Instructions for how CME credits can be earned appear on
the last page of the Table of Contents.

Massive Blood Loss and Transfusion in

Obstetrics and Gynecology
Joseph T. Santoso, MD,* Brook A. Saunders, MD,†
and Ken Grosshart, MD‡
*Associate Professor and Director, Division of Gynecologic Oncology, The West Clinic, University of
Tennessee Health Science Center; Memphis, Tennessee; †Resident Physician, University of Tennessee Health
Science Center, Department of Obstetrics and Gynecology, Memphis, Tennessee; and ‡Clinical Assistant
Professor, University of Tennessee Health Science Center, Baptist Memorial Hospital, and Medical Director
of Blood Bank, Department of Pathology, Memphis, Tennessee

Massive perioperative or periparturitional bleeding occasionally occurs in obstetric and gyne-

cologic patients. Placenta previa, uterine atony, and ectopic pregnancy are just a few examples of
many conditions that could predispose patients to significant blood loss. Therefore, it is important
for physicians specializing in obstetrics and gynecology to be proficient in managing episodes of
massive hemorrhage and the practice of the most commonly used blood components. We review
and update the management of massive hemorrhage for obstetrics and gynecologic patients. In
addition, we explore blood component therapy, its risks and benefits.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Learning Objectives: After completion of this article, the reader should be able to explain the necessity
of being proficient in managing episodes of massive hemorrhage, list the indications for use of various
blood components, and summarize the risks and benefits of blood component therapy.

MASSIVE HEMORRHAGE PROTOCOL minimal changes in pulse, blood pressure, or respi-

ratory rate in most healthy patients. A blood loss of
The definition of massive hemorrhage is subjec-
15% to 30% (class II hemorrhage) produces symp-
tive. However, many agree that it can be practically
defined as symptomatic bleeding that requires an toms of tachycardia, tachypnea, and narrowing of
emergency intervention to save the patient’s life or pulse pressure. This decrease in pulse pressure
acute loss of more than 25% of the patient’s blood mainly is the result of a rise in diastolic pressure from
volume (1). The physiology of bleeding and re- catecholamine-induced vasoconstriction. In addition,
sponses to hemorrhage are well known (2). The nor- subtle mental status changes and mild decrease of
mal blood volume is approximately 8% of body urine output may be observed. A blood loss of 30%
weight (4.8 L in a 60-kg adult). A blood loss up to to 40% (class III hemorrhage) causes increasing car-
15% of blood volume (class I hemorrhage) results in diovascular instability with marked hypotension and
clouded sensorium. A blood loss of more than 40%
The authors have disclosed that they have no financial relation-
ships with or interests in any commercial companies pertaining to (class IV hemorrhage) is a life-threatening situation
this educational activity. with marked depression of mental status, severe hy-
Wolters Kluwer Health has identified and resolved all faculty potension, minimal urine output, and severe periph-
conflicts of interest regarding this educational activity. eral vascular constriction. Patients presenting with
Reprint requests to: Joseph T. Santoso, MD, Associate Professor
and Director, Division of Gynecologic Oncology, The West Clinic,
class III or IV hemorrhage can die of multiorgan
University of Tennessee Health Science Center, 100 North Hum- failure unless resuscitation is accomplished in the
phreys, Memphis, TN 38120. E-mail: jsantoso@westclinic.com. first 1 to 1.5 hours.
827
828 Obstetrical and Gynecological Survey

It is very important that a rapid, organized, and taining a hemoglobin (Hb) of ⬎10 g/dL is rarely
systematic protocol be adopted to handle major hem- indicated. Furthermore, Hb ⬍7 g/dL is probably a
orrhage. It should be similar to a cardiac arrest pro- good indication for red cell transfusion as concluded
tocol (Advanced Cardiac Pulmonary Resuscitation by the NIH consensus statement (3). Thus, the target
Protocol). We recommend a Hemorrhage Protocol of Hb during resuscitation is probably between 7 and
similar to the one outlined in Figure 1 for massive 10 g/dL depending on the patient’s condition (age,
bleeding in obstetrics and gynecologic patients. At cardiac status, type of bleeding, acuteness of hemor-
the onset of massive bleeding, the situation must be rhage, and so on). Even after achieving the target
recognized as an emergency and the resuscitation Hb, scrupulous attention to intravascular volume
protocol initiated. Hospital staff and physicians measurement and maintenance is critical because ac-
should quickly designate a team leader who will curate measurement of a patient’s blood volume con-
direct and coordinate the resuscitation. Good com- tinues to be challenging during the resuscitation.
munication between team members and with outside Estimated blood loss is well known to be very inac-
consultants is very important. The team leader should curate (4). In acute blood loss, the baseline Hb may
obtain a quick history and instruct others to secure be normal in the face of a severely depleted blood
the airway, obtain intravenous access with 2 large- volume. In contrast, measured Hb level may be in-
bore venous catheters, collect appropriate initial lab- accurately lower than the actual red blood cell vol-
oratory tests, inform the blood bank, and initiate ume in a patient who received an excessive amount
intravenous fluid boluses. Good teamwork with a of crystalloid. Having serial Hb levels may help
knowledgeable, practiced, and well-led team is more reduce this potential inaccuracy; testing post-PRBC
likely to result in a successful outcome than a frantic, infusion can be done with reliable incremental
disorganized response to massive blood loss. change at 15 minutes after completion of a transfu-
The team leader should try to diagnose the under- sion episode (5).
lying disorder. A decision to go to surgery needs to The team needs to monitor the response of the pa-
be made early because the underlying bleeding sites tient. Persistent cardiovascular instability (tachycardia,
may need to be stopped surgically. Additional per- narrowing of pulse pressure, hypotension) after fluid
sonnel and appropriate equipment need to be re- boluses indicates an underestimated volume loss or
quested. If indicated, the operating room should be ongoing significant hemorrhage requiring further resus-
notified. The team should also anticipate the need for citation. Widespread bleeding from intravenous and
blood and components (fresh-frozen plasma [FFP], incision sites at the outset suggests the presence of
cryoprecipitate) early because it may take approxi- disseminated intravascular coagulation (DIC), which
mately 30 minutes to 1 hour to type and cross blood can be confirmed by the baseline hemostatic parameters
and to thaw FFP and cryoprecipitate. Thus, an early (platelet count, fibrinogen, prothrombin time, activated
call to alert the blood bank will help to ensure an partial thromboplastin time, antithrombin III, and fibrin
adequate supply of blood products. split products/D-dimer, if available). Early DIC may be
Studies have reported no difference in survival for related to a labor-induced amniotic fluid embolism,
trauma patients treated with crystalloid versus colloid sepsis from a significant bacterial infection, or retained
(1). Similar studies have also suggested that colloid products of conception. FFP, which has all coagulation
resuscitation might have a harmful effect of delayed factors, should be infused. DIC-type parameters appear-
postresuscitation diuresis and higher incidence of ing in later laboratory assessments must be promptly
postresuscitation hypertension. Crystalloids are more distinguished from hemodilution (dilutional coagulopa-
readily available and are less expensive. In practice, thy) principally by clinical comorbidities and compari-
crystalloids are infused in volume boluses calculated sons of baseline with follow-up prothrombin times and
at 3 times the estimated blood loss. Colloid indeed platelet counts. True late DIC is invariably the result of
can achieve a higher intravascular oncotic pressure sustained tissue hypoxia and hypothermia from inade-
with a smaller volume than crystalloid. quately resuscitated hemorrhagic shock.
Red blood cell transfusion is mainly in the form of During massive bleeding, clotting factors and
packed red blood cells (PRBCs) (see component platelets are lost as well as red cells. Rapid transfu-
therapy subsequently). It is not indicated in the first sion of PRBC and crystalloid may further result in
stages of resuscitation when volume repletion is the dilution of clotting factors and platelets. However,
key. It is indicated to improve O2-carrying capacity. infusion of FFP, cryoprecipitate, and platelets should
Indirectly, this is translated to achieve a target he- be based on laboratory testing and clinical findings
moglobin level. Most literature confirms that main- rather than a set formula. FFP should be given in a
Massive Blood Loss and Transfusion in Ob/Gyn Y CME Review Article 829

Fig. 1. Treatment algorithm for massive bleeding.

830 Obstetrical and Gynecological Survey

TABLE 1
Blood component summary
Component Indication Notes
Packed red blood cells To improve O2-carrying capacity Raise Hb 1 g/dL
Fresh-frozen plasma Replace clotting factors PT and/or PTT ⬎1.5 ⫻ Start with 2 U FFP or 15–20 mL/kg ideal body
upper normal weight
Cryoprecipitate Fibrinogen ⬍75–100 ␮g 1 U/10-kg body weight with fibrinogen ⬍75
Platelets Platelets ⬍50,000 Increase platelets 5000 –10,000/mm3 per unit
Albumin Volume replacement, bind bilirubin in newborns Use 5% albumin
albumin ⬍1.0 g/dL (total protein ⬍4.0)
PT indicates prothrombin time; PTT, partial thromboplastin time; Hb, hemoglobin; FFP, fresh-frozen plasma.

patient who is clinically showing widespread capil- The circle of resuscitation and reassessment of the
lary bleeding and/or abnormal international normal- patient’s response to treatment is crucial. As vital signs
ized ratio results. Hemostasis is usually maintained stabilize, the resuscitation is going in the right direction.
when coagulation protein is approximately 25% of However, destabilization of vital signs requires a more
normal. Because one unit random donor FFP (in an aggressive resuscitation. An invasive diagnostic line
adult) will increase the clotting protein levels by 8%, such as a central venous pressure or pulmonary artery
2 units FFP is a good starting number to transfuse. A catheter should be inserted to evaluate the adequacy of
routine practice of infusing FFP after a certain units fluid resuscitation. If the catheter suggests that intravas-
of PRBC may lead to excess transfusion and wastage cular fluid is adequate but hypotension persists, the next
of FFP. Platelet transfusion is indicated in a bleeding step is to use vasopressors. Most clinicians start with
patient with a platelet count of ⬍50,000. Usually 6 dopamine 4 to 5 ␮g/kg/min intravenously and titrate to
units are given and the platelet count rechecked 15 achieve adequate blood pressure (ie, mean arterial pres-
minutes later. In nonbleeding patients, prophylactic sure of 80 mm Hg). Once dopamine has been titrated to
platelet infusion is rarely indicated until the platelet the maximum of 20 ␮g/kg/min, persistent hypotension
counts are less than 10,000 (6,7). will require the addition of norepinephrine or epineph-
Permissive hypotensive resuscitation has been pro- rine. The use of vasopressors must be done with great
moted by some instead of conventional aggressive caution in hypovolemic shock. The vasopressors may
fluid resuscitation (8). The underlying premise is that lead to higher blood pressure but at the expense of
higher blood pressure in uncontrolled hemorrhage diminished organ perfusion. It cannot be overempha-
results in more blood loss. Aggressive crystalloid sized that control of the bleeding site combined with
infusion may cause further dilution of clotting fac- fluid and blood resuscitation should be the primary
tors, thus more blood loss. Although the goal in means of treatment of hypovolemic shock.
animal studies is the difference in blood product use
and dilutional coagulopathy between the 2 situations,
BLOOD COMPONENT THERAPY
this is still a very controversial subject in humans and
awaits further studies before its adoption to clinical Many bleeding patients only require fluids and red
practice. The present standard of therapy continues to cell transfusion. Thus, whole blood transfusion,
use aggressive crystalloid and blood product therapy which has red cells, clotting factors, and protein, is
in severely bleeding patients. usually not indicated. Obstetricians and gynecolo-
Another common complication of massive bleed- gists should be prepared to order the appropriate
ing is hypothermia. Hemorrhagic shock impairs per- blood component therapy for each individual patient.
fusion and metabolic activity. Further loss of heat is In this section, we explore individual commonly used
through conduction because of wet clothing or be- blood components, risks, and benefits (see Table 1).
cause clothing has been removed. When core body
temperature drops below 32°C, patients are prone to
Packed Red Blood Cells
cardiac arrhythmias and defective coagulation. Con-
sequently, infused fluid and blood should be warmed Packed red blood cells are the component of choice
to the body temperature. Warm blankets and dry for anemic hypoxia in most clinical situations. A
clothes should cover the patient at all times after single unit of PRBCs contains 300 mL of volume
examination is completed. consisting of mostly red cells mixed with preserva-
 Massive Blood Loss and Transfusion in Ob/Gyn Y CME Review Article 831

tives and anticoagulant (citrate, phosphate, dextrose, one currently being used in the United States. These
and adenosine). In larger hospitals, group O PRBCs methods of treatment are effective in inactivating
are usually available within 5 minutes and group- lipid-encapsulated viruses (hepatitis B and C, HIV,
specific PRBCs in 10 to 15 minutes; however, cross- human T-cell lymphotrophic virus, cytomegalovirus,
matched PRBCs require 45 to 50 minutes if there are Epstein-Barr virus). However, neither method is ef-
no antibody problems. Because of the viscosity of fective for viruses that do not have a lipid-based
concentrated red cells (hematocrit around 70%), capsule (hepatitis A, parvovirus) or prions (9,10).
PRBCs can be diluted with 100 mL normal saline
when a rapid transfusion rate is needed. Ringers Cryoprecipitate
lactate solution should not be mixed with PRBCs Cryoprecipitate is prepared by thawing a unit of
because its calcium content may precipitate when it FFP at 4°C and collecting the formed precipitate in a
interacts with citrate preservative. In the absence of concentrated volume of 10 to 15 mL/bag. Each bag
ongoing bleeding, a single unit of PRBCs should or unit contains 200 to 300 mg of fibrinogen and 100
raise the hematocrit by 3 percentage points. Although units of factor VIII (80–100 IU), von Willebrand
more expensive, PRBCs can be leukoreduced for factor (vWF; 80–100 IU), factor XIII (50–100 IU),
use in patients who have experienced a prior febrile and 55 mg fibronectin in a final volume of 15–20
transfusion reaction. PRBCs have no platelets mL/bag. It carries the same infectious risk as a unit of
present and only approximately 10 to 15 mL of red cells.
residual plasma. Cryoprecipitate is used most often in the treatment
Fresh-Frozen Plasma of congenital and acquired deficiencies of fibrinogen
and factor XIII and is often used in patients with von
Fresh-frozen plasma is the component of whole Willebrand disease and uremic platelet dysfunction.
blood that remains once the platelets and cellular In massive transfusion, it is used mainly to comple-
elements are removed. FFP is prepared from single ment FFP infusion when the patient’s fibrinogen
units of whole blood (random-donor FFP with a
level is very low. Ten bags of cryo (obtained from 10
volume of approximately 250 mL) or from plasma
units of plasma) contain approximately 2 g of fibrin-
collected by apheresis techniques (jumbo FFP with
ogen, and will raise the fibrinogen level at least 65 to
volume approximately 800 mL, available only from
70 mg/dL in a 70-kg recipient.
blood centers). It is frozen at ⫺18° to ⫺30°C.
FFP contains all of the coagulation factors and Because of viral transmission risk, cryoprecipitate
other proteins present in the original unit of blood. It should not be used in the treatment of hemophilia.
is used to replenish multiple clotting factors in mas- Pasteurized factor VIII concentrates with and without
sive transfusion, DIC, and coumadin effect reversal. von Willebrand factor and factor VIII from recom-
FFP should not be used as a source of albumin or binant DNA techniques are now the recommended
other nutrients or as a volume expander. FFP should treatments. Cryoprecipitate does contain large von
be ABO-compatible, but does not have to be cross Willebrand’s components, and it may be used to treat
and typed or RH-specific. vWF deficiency if no other therapies are available.
Hemostasis can be achieved when the activity of Platelets
coagulation factors is at least 25% of normal, in the
absence of other coagulopathies. A prothrombin time Platelets are obtained from whole blood from mul-
and/or partial thromboplastin time of 1.5⫻ the upper tiple donors or by apheresis collection (6–9 single-
limit of normal indicates the need for FFP. Because unit equivalents). Transfusion of one single unit of
the plasma volume in adults is approximately 40 platelets will increase the platelet count approximately
mL/kg, this requires a dose of FFP of approximately 5000 to 10,000/mm3 in the average individual. The
15 ml/kg. One unit of FFP/20 kg body weight is a increase will be less in a patient with antiplatelet
good starting number to use for initial treatment. FFP antibodies, and single-donor or HLA-matched platelet
has about the same infectious, allergic, and volume transfusions will provide a better response in these
overload risks as PRBC. patients. ABO typing of platelets for transfusion is
Attempts are underway to increase the safety of not essential. However, ABO-incompatible platelets
FFP with regard to virus inactivation with one of 2 may have a shortened survival. In women of child-
methods. The first uses a solvent–detergent method, bearing age, Rh-negative patients should receive Rh-
and the second uses the use of methylene blue and negative platelets, if available. If none are available,
visible light. The solvent–detergent method is the they should be transfused with Rh-positive platelets
832 Obstetrical and Gynecological Survey

and given Rh immune globulin to compensate for the toms associated with the benign and serious reactions
amount of RBC contamination within the platelets. are often similar. Complications to blood transfusions
Platelet transfusions are indicated for correction of occur between 1% and 6% of the time and are more
spontaneous bleeding from thrombocytopenia, in the frequently associated with patients with underlying he-
presence of severe thrombocytopenia, or a dysfunc- matologic and oncologic disorders (13,14). We review
tional platelet disorder before an invasive procedure transfusion complications in 3 subsections: infectious,
(11). The goal of transfusion should reach platelet immunologic, and miscellaneous risks.
count approximately 100,000/mm3. A platelet count
of 50,000/mm3 is usually adequate if the platelets
are normal. However, platelet dysfunction is com- Infectious Risks
mon in massive transfusion and hypothermic patients Viral
(1). Platelet dysfunction may also be the result of a
rapid destruction such as idiopathic thrombocyto- The primary concern among the public regarding
penia purpura (ITP-platelet autoantibodies), drug- viral contamination of blood is related to the human
related thrombocytopenia, hypersplenism, DIC, sepsis/ immunodeficiency virus (HIV); however, other vi-
fever, immune complex diseases, and allosensiti- ruses play a role. These include hepatitis B and C
zation (transfusion-related platelet alloantibodies). (HBV/HCV), human T-cell lymphotrophic viruses
Platelet transfusions also are ineffective in cases (HTLV-I/II), Epstein-Barr virus (EBV), cytomegalo-
of uremia resulting in platelet dysfunction and in virus (CMV) and now West Nile virus (see Table 2).
thrombotic thrombocytopenia purpura (TTP) and HIV has been the major fear among the public with
hemolytic-uremic syndrome (HUS) unless the patient regard to blood transfusions. The risk has not been
is experiencing life-threatening bleeding. Platelet eliminated, but it has been substantially decreased
transfusion in patients with TTP/HUS can induce over the past few years with the introduction of
further platelet destruction. nucleic acid amplification tests (NAT) and the addi-
In the nonbleeding patient, there is debate over the tion of antibody testing. The current risk for acquir-
lower platelet limit at which a patient should be ing HIV from transmission of blood or blood
transfused. Many physicians use a level of 20,000/ components is one in 2.3 million (15). Transfusion-
mm3 before platelet transfusions are initiated; how- transmitted hepatitis has also undergone a dramatic
ever, recent studies have found that there is very little reduction as a result of the implementation of mul-
difference clinically if a patient is not transfused until tiple antibody tests and NAT. HCV, the genetically
a platelet count of 10,000/mm3 is reached (6,7). diverse RNA virus, has decreased over the last 14
years from one in 3000 to one in 1.9 million for
Albumin repeat donors and one in 1.4 million in all donors in
Albumin is used for volume replacement and to the United States. Likewise, HBV, the DNA virus,
bind bilirubin in hemolytic disease of the newborn. It averages one in 205,000 in repeat donors and one in
comes in 5% and 25% solution. It does not carry an 144,000 in all donors (16).
infectious risk because its preparation involves heat Epstein-Barr virus, a herpes-group virus, is the
treatment. Low perioperative serum albumin levels primary pathogen associated with infectious mononu-
correlate with a poor prognosis; however, infusion of cleosis. The majority of the donor population has the
albumin has not been shown to improve the outcome
(12). Albumin should not replace feeding to improve TABLE 2
a patient’s nutritional status. It is expensive and less Infection risks associated with transfusions (16,39)
efficacious than parenteral nutrition. Other human Infection Associated Risk
protein products have cytokine/kinin-related side ef- Hepatitis A 1:1 million
fects and are no longer used. Hepatitis B 1:144 –205 thousand
Hepatitis C 1:1.4 –1.9 million
HIV 1:2.3 million
TRANSFUSION COMPLICATIONS Human T-cell lymphotropic 1:250,000 –2 million
virus I/II
Most reactions that occur during transfusions of West Nile virus Rare
blood components are benign. However, some reac- Parasitic diseases (babesiosis, Rare
tions during the infusion of blood products can be Chagas, Lyme disease,
serious, and these reactions may not be immediately malaria)
Creutzfeldt-Jakob disease Rare
recognized as a result of the fact that the initial symp-
 Massive Blood Loss and Transfusion in Ob/Gyn Y CME Review Article 833

antibody for EBV. Because EBV transfusion-related the United States is very rare. Immigrants and visi-
infection is often asymptomatic, blood donors are not tors to the United States are the main source for
routinely screened for EBV. However, people with ac- malaria contamination. When they are excluded from
tive EBV are discouraged from donating blood. donating blood for 6 months unless they had received
West Nile virus (WNV) first appeared in 1999 in antimalarial prophylaxis, the transmission of malaria
North America, forming the first outbreak affecting is extremely rare. Transmission of Lyme disease is
66 patients in New York City. With rapid develop- theoretically possible; however, it has not been re-
ment of nucleic acid testing, 9388 patients were ported to our knowledge. Gram-negative bacteria
identified with WNV infection and 246 of deaths such as P. fluorescens and Y. enterocolitica thrive at
were attributed to WNV. During that year, 6 blood the cool storage temperature of blood and use citrate
recipients were confirmed of getting transfusion- as an energy source. Their contamination of blood is
related WNV (16). The American Red Cross then rare. Approximately 8 to 10 deaths are reported as a
implemented WNV testing in high-incidence areas, result of septicemia per 10 million blood transfusions
resulting in removal of 1000 potentially WNV- (platelets 1:1000–3000 with mortality 1:140,000;
infected blood components. No cases of transfusion- PRBCs 1:5 million with mortality 1:8 million) (18).
related WNV were recorded among recipients of the
tested blood (17).
Immunologic Risks
HTLV I/II are retroviruses that live in human T-cells
and can be transmitted through blood transfusions. Immunologic reactions to transfusions are acute he-
HTLV-I can cause T-cell leukemia and tropical spastic molytic reactions, delayed hemolytic reactions, febrile
paraparesis (TSP). Until recently, HTLV-II had not reactions, allergic reactions, transfusion-related acute
been linked to any known illness, but it has now been lung injury (TRALI), and posttransfusion purpura.
shown that HTLV-2 is related to some type of myelop-
athy and TSP as well.
Acute Hemolytic Reactions
CMV is a member of the herpes virus family and
also causes a mononucleosis-type illness. It is be- Acute hemolytic reactions are an uncommon oc-
lieved that the virus remains in the white blood cells currence associated with transfusions and occur as a
for life. It is not possible to identify which CMV- result of the recipient having preformed antibodies
positive donor blood is infectious, thus providing the and subsequently destroying the donor red blood
recommendation that CMV antibody-negative blood cells. Fatal transfusion reactions are rare but can
or so-called “CMV-safe” (CMV-seronegative or leu- occur with as little as 30 mL of incompatible blood
koreduced) blood be transfused to immunocompro- and usually occur as a result of clerical errors result-
mised patients and infants. CMV does not usually ing in the transfusion of the wrong blood or, less
cause serious infection in healthy adult blood recip- commonly, blood that has been improperly typed and
ients. However, transfusion-transmitted CMV may crossmatched (risk 1:12,000) (19).
potentially cause complication and death in immu- The classic triad of fever, flank pain, and reddish-
nocompromised patients such as premature low- brown urine is rarely seen. Some early signs and
birth-weight (⬍1500-g) babies born to seronegative symptoms for an acute hemolytic reaction include
mothers, seronegative transplant recipients, and pa- pain at the infusion site, fever, chills, back/substernal
tients with AIDS. pain, mental status changes, dyspnea, cyanosis, and
DIC. Shock, acute renal failure, and death can ensue
if the reaction is not recognized and treated; if
Bacterial and Other Infectious Risks
a hemolytic reaction is suspected, the transfusion
The risk of complications secondary to a bacte- should be stopped immediately, and the patient as
rial infection from blood products is small. The well as the blood being transfused should be exam-
etiologies include unrecognized, asymptomatic in- ined. Blood should be sent for hemoglobin, bilirubin,
fections (Yersinia enterocolitica, malaria, Lyme haptoglobin, creatinine, and Coombs testing; the
disease, Pseudomonas fluorescens), introduction urine should be examined for hemoglobin products.
of skin flora at venipuncture (Gram-negative and The patient should be supported with intravenous
Gram-positive organisms), and entry of contami- fluid replacement to maintain urine output greater
nants during processing. than 150 mL/hour (3000 mL/m2 per day). Treatment
Malaria is common in Central America, Asia, and with mannitol (initial dose 100 mL/m2 of 20% solu-
Africa; however, its presence in the blood supply in tion over 30–60 minutes; maintenance dose 30 mL/m2
834 Obstetrical and Gynecological Survey

per hour ⫻ 12 hours), Lasix pulses, dopamine & Specialty Pharmaceuticals, New Brunswick, NJ) is
(3–5 ␮g/kg per hour), and urine alkalinization should efficacious in prophylaxis.
be considered to protect against nephropathy.
Allergic Anaphylactic Reactions
Allergic reactions result from the infusion of a
Delayed Hemolytic Reactions blood product to which the patient has preexisting
Delayed hemolytic reactions occur more frequently antibodies. This can occur without any history of a
and occur following reexposure to an antigen previ- transfusion. The symptoms can range from mild ur-
ously encountered as a result of transfusion, trans- ticaria and pruritus (risk 1:250) to severe anaphylaxis
plantation, or pregnancy (risk 1:4000–12,000). The (risk 1:26,000–47,000). Symptoms of shock, hypo-
antigen is usually a member of the Kidd or Rh class. tension, angioedema, and respiratory distress in a
On reexposure to the antigen, the antibodies increase patient receiving a transfusion call for an immediate
rapidly in titer. Usually a gradual, extravascular-type and aggressive response, because they may represent
hemolysis of the donor erythrocytes occurs; but, de- a life-threatening emergency.
pending on the antigen group, hemolysis may be If an allergic reaction occurs, the transfusion should
immediate. Clinicians may notice increasing anemia, be stopped. Supportive care should be initiated first
spherocytosis on blood smear, mild fevers, increas- with airway control and oxygenation along with H1-
ing unconjugated bilirubin levels, jaundice, hemoglo- blockers such as 25 to 75 mg diphenhydramine hy-
binuria, and decreased haptoglobin. The diagnosis is drochloride (Benadryl; Pfizer Inc., New York, NY)
typically made when blood for further transfusions is (if severe, add H2-blockers and hydrocortisone intra-
ordered, and antibodies are noted in the antibody venously). Intravenous fluids should be given for vol-
screen. The extravascular reactions are more indolent ume control and vasopressors (epinephrine) should be
in nature and usually require no further treatment, initiated with sustained hypotension or wheezing.
whereas the immediate reactions are treated like Further transfusions should consist of washed red
acute hemolytic reactions. However, it should be cell and platelet products if simple H1-blocker treat-
noted that future transfusions can be more harmful in ment fails. Recurrent symptoms should prompt eval-
nature, and the offending antigen should be recorded uation for IgA deficiency.
(The Blood Bank has extensive historical data and
can be consulted.). Transfusion-Related Acute Lung Injury
TRALI is not a rare complication, occurring in
approximately one in 2000 to 5000 transfusions, and,
Febrile Reactions
in the past 2 years, it is the leading cause of trans-
Febrile reactions are the most common reaction fusion-related death in the United States (22,23). It
and occur in approximately 1%. Febrile reactions has been reported in patients between the ages
occur in response to the transfusion of PRBCs and of 9 days and 73 years of age and occurs equally in
result from antileukocyte antibodies derived from both sexes (24–26). The symptoms associated with
previous blood exposures and from the cytokines TRALI are acute respiratory distress, hypoxemia,
such as IL-1, -8, and TNF-␣, which accumulate in hypotension, fever, and pulmonary edema without
the stored blood (14,20,21). Febrile reactions are the presence of left-sided heart failure (24). Symp-
self-limiting, and patients may or may not be at risk toms are evident within 6 hours after the initiation of
for a recurrence of a febrile reaction. Hemolysis from the transfusion, usually within 1 to 2 hours. Central
a hemolytic reaction must be excluded first in the venous pressures associated with TRALI are normal,
diagnosis of a febrile reaction, because fever is a distinguishing it from volume overload associated
common symptom associated with acute hemolytic with the transfusion. TRALI is clinically similar to
reactions. Chills can be treated with meperidine (De- acute respiratory distress syndrome (ARDS); how-
merol; Wyeth, Madison, NJ). Because of the difficulty ever, TRALI has a much better prognosis. Death
in quickly excluding bacterial contamination or early occurs in less than 10% of patients, and recovery is
transfusion-related acute lung injury (TRALI; Vida in- usually complete within 96 hours.
fra), it is our policy to discontinue the transfusion. Use The pathogenesis associated with TRALI is associ-
of leukocyte-reduced products and premedication ated with perhaps 2 nonoverlapping mechanisms. The
with 1 g acetaminophen (Tylenol; McNeil Consumer first event is the clinical condition (incubating infection,
 Massive Blood Loss and Transfusion in Ob/Gyn Y CME Review Article 835

stress of shock, coronary artery bypass grafting, im- excess citrate may bind to plasma calcium and causes
mune complex/compliment activation) of the patient severe hypocalcemia. Additionally, each millimole
that results in at least some pulmonary endothelial ac- of citrate generates 3 mEq of bicarbonate; thus, ap-
tivation and neutrophil priming producing an interac- proximately 23 mEq of bicarbonate can be generated
tion. The second insult is the transfusion of a biologic per unit of blood. If the patient’s renal function is
agent (including lipids from stored buffy coat and compromised, excess bicarbonate cannot be excreted
leukocyte-specific antibodies), which is believed to and metabolic alkalosis may ensue.
contain leukocyte antibodies (HLA-I, HLA-II, anti-
granulocyte), which further activates the neutrophil and
restricts its nonspecific toxicity to the endothelium, Metabolic Alkalosis
producing ARDS through a limited intrapulmonary, Secondary to the presence of the citric acid in the
intravascular, inflammatory reaction (22,27,28). PRBC, the pH of a unit of blood is approximately
The treatment for TRALI is supportive care. Some 7.10. The PRBC pH further decreases during storage
attempts at treatment with high-dose steroid therapy approximately 0.1 unit/week secondary to the pro-
have been tried but generally felt to be unsuccessful duction of lactic and pyruvic acids. However, acido-
(24). The patients improve clinically as the lung injury sis does not occur when the patient is transfused as
resolves. Intubation and mechanical ventilation with long as tissue perfusion is maintained. Conversely,
increased levels of inspired oxygen and positive end- metabolic alkalosis may occur as a result of citrate
expiratory pressure are needed in severe cases. More toxicity, as discussed previously. Metabolic alkalosis
mild cases can often be managed with supplemental may also result in the net movement of potassium
oxygen only. Generally, diuretics are avoided because into the cells in exchange for hydrogen ions resulting
hypotension from intravascular volume depletion can in hypokalemia.
occur with excessive diuresis (29).
The donor responsible for the initial episode of
TRALI should be identified, and the patient should Hypocalcemia
receive no further blood products from that person.
Future transfusions are felt to be safe as long as the Infusion of citrate can also lead to the direct bind-
blood products are from a different donor (30–33). ing of ionized calcium. Massive blood transfusions
can result in clinical hypocalcemia and subsequent
hypotension, tetany, hypotension, and cardiac ar-
Posttransfusion Purpura rhythmias (36). To prevent hypocalcemic complica-
Posttransfusion purpura is rare (risk 1:143,00– tions, serum calcium should be tested for every 5 to
294,000) and occurs approximately 1 week after a 7 units of PRBC. If it is low, the patient should be
transfusion. It is thought to be a type of delayed treated with 10 to 20 mL of 10% calcium gluconate
hypersensitivity transfusion reaction involving the or 2 to 5 mL of 10% calcium chloride. Careful
platelets. Susceptible patients are transfused platelets monitoring of the patient’s ionized calcium should
with the HPA-1a antigen. When the patients lack this also be practiced to avoid excessive calcium infusion
antigen, they develop an alloantibody that destroys the and subsequent hypercalcemia.
transfused platelets and also their own platelets as a
result of an unknown but probably crossreactive
mechanism. The treatment is typically with high Hyperkalemia
doses of intravenous immunoglobulin and pulse cor- The occurrence of hyperkalemia after the transfu-
ticosteroids; plasmapheresis may be useful, but its sion of PRBC is a rare event. Care must be taken
effects are variable and delayed (average 12 days). when transfusing neonates and patients with chronic
Patients should receive HPA-1a-negative blood prod- renal insufficiency. Hyperkalemia can occur as a
ucts, but these are not readily available (family mem- result of passive diffusion of potassium out of the red
bers may be a source) (34,35). blood cells by approximately 1 mEq/L per day. This
potassium is not transported back into the cells and,
Miscellaneous Risks as a result, is transfused to the patient along with the
PRBC. The infused potassium is usually transported
Citrate Toxicity
into the cells, diluted with other volume infusions,
Citrate is used as an anticoagulant preservative for and excreted in the urinary system. If necessary,
red blood cell preparations. In massive transfusion, recently collected blood, whole blood, and blood
836 Obstetrical and Gynecological Survey

washed to remove the potassium can be used for the CONCLUSION

transfusion.
Episodes of massive hemorrhage in the field of
obstetrics and gynecology are not a frequent occur-
Hypothermia rence; however, many patients have conditions and
risk factors potentially requiring transfusions, and
For preservation, blood products are stored in a physicians need to be adept in recognizing the need
refrigerated state usually from 1° to 6°C, and hypo- when it occurs. Clinicians should be able to evaluate
thermia can result secondary to massive transfusions. the hemorrhage associated with degrees of shock and
The core temperature can be decreased quickly re- have a treatment protocol in place to effectively treat
sulting in arrhythmias (37). Coagulation abnormali- their patients. Having a treatment plan, such as ours
ties and peripheral vasoconstriction can result, which in Figure 1, can make the treatment of massive hem-
can lead to decreased tissue perfusion. Therefore, a orrhage and the utilization of blood products much
blood warmer should be used to warm the blood as safer for the patient as well as easier on the physi-
close to the core temperature as possible. cians and housestaff involved.

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