Kuliah Blok Bleeding Disorders

Bleeding Disorder
Sony Wicaksono
Susanto Nugroho
Lab/SMF Ilmu Kesehatan Anak
FK Universitas Brawijaya/RS Dr. Saiful Anwar
Hemostasis
Hemostasis
Hemostasis
ITP: Immune
Thrombocytopenic Purpura
An
autoimmune disorder characterized

by a low platelet count and
mucocutaneous bleeding
The estimated incidence is 100 cases
per 1 million persons per year, and
about half of these cases occur in
children
Classified as primary or as secondary to
an underlying disorder and as acute (of
six months or less in duration) or chronic
ITP: Pathophysiology
ITP: Clinical Features
ITP: Clinical features
Laboratory Findings
The
platelet count is usually 10-50 x

109/L.
The blood film shows reduced numbers of
platelets, those present often being large.
The bone marrow shows normal or
increased numbers of megakaryocytes.
Sensitive tests are able to demonstrate
specific antiflycoprotein GPIIb/IIIa or GPIb
antibodies on the platelet surface or in
the serum in most patients.
Antibody Measurements
Detection of PlateletSpecific Antibodies
with a MonoclonalAntigenCapture Assay
In this test, platelets from
a patient suspected of
having immune
thrombocytopenic
purpura are coated with
an autoantibody in this
case, an autoantibody
against the glycoprotein
IIb/IIIa complex (orange).
ITP: Management
Chronic
Refractory
ITP
Hemostasis
Hemophilia
Hemophilia
is one of the oldest described genetic

diseases & congenital deficiency of factor VIII (FVIII),
and hemophilia B is a consequence of a congenital
deficiency of factor IX (FIX).
This deficiency results in insufficient generation of
thrombin by FIXa and FVIIIa complex through the
intrinsic pathway of the coagulation cascade.
They account for 90-95% of severe congenital
coagulation deficiencies.
Hemophilia A(HA), which comprises approximately
80% of cases,is considered the classic form of
hemophilia, and hemophilia B (HB) is termed
Christmas disease.
Hemophilia:
Epidemiology
Hemophilia
A is approximately 1 case per 5000 male

individuals, with approximately one third of affected individuals
not having a family history
Hemophilia
B occurs in 1 case per 25,000 male individuals and

represents one fourth to one fifthof all patients with hemophilia
Both
forms of hemophilia are sex-linked coagulopathies because

they are inherited as X-linked traits
Female
individuals who carry the affected genes usually do not

have bleeding manifestations
Hemophilia
groups.
A and hemophilia B are found in all ethnic and racial
Hemophilia: Inheritance
Pathophysiology
Pathophysiology
Persons with 1-5% normal factor (0.01-0.05 IU/mL) are considered to have moderately sev
hemophilia. Persons with more than 5% but less than 20% normal factor (>0.05 to <0.20 IU/mL)
considered to have mild hemophilia. Clinical bleeding symptom criteria have been used becau
patients with FVIII or FIX levels less than 1% occasionally have little or no spontaneous bleeding a
appear to have clinically moderate or mild hemophilia. Furthermore, the reverse is true for patie
with procoagulant activities of 1-5%, who may present with symptoms of clinically severe disease.
Hemophilia:
Classification
Table 1. Correlation of Coagulation Factor Activity and Disease Severity in Hemophilia A

Hemophilia B
Coagulation factor activity
(% of normal)
<1
Clinical manifestation
Severe disease
Frequent spontaneous bleeding episodes from early life
Joint deformity and crippling if not adequately treated
15
Moderate disease
Post-traumatic bleeding
Occasional spontaneous episodes
5 20
Mild disease
Post-traumatic bleeding
CLINICAL FEATURES
Approximately 30-50% of patients with severe hemophilia present with manifestations
neonatal bleeding (eg, after circumcision). Approximately 1-2% of neonates have intracran
hemorrhage. Other neonates may present with severe hematoma and prolonged bleeding from
Hemophilia: Clinical
Features
Hemophilia: Clinical
Features
!
!
Usually, von Willebrand factor (vWF) levels are also measured. The combination of low FVIII and
low vWF may indicate vWF deficiency as the primary diagnosis.
Because FVIII and FIX are large molecules that do not cross the placenta, the diagnosis can be
made at birth with quantitative assay of coagulation factors in the cord blood.
Early diagnosis of FIX deficiency is complicated by the physiologic reduction of vitamin K
dependent factors in young infants.
Laboratory Findings
!
Table 2. Main Clinical and Laboratory Findings in Hemophilia A and Hemophilia B

Hemophilia A
Hemophilia B
Inheritance
Sex-linked
Sex-linked
Main site of hemorrhage
Muscle, joints, post-trauma or

postoperative
Muscle, joints, post-trauma or

postoperative
Platelet count
Normal
Normal
Bleeding time
Normal
Normal
Prothrombine time
Normal
Normal
Partial thromboplastin time
Prolonged
Prolonged
Factor VIII
Low
Normal
Factor IX
Normal
Low
vWF
Normal
Normal
Normal
Normal
Ristocetin-induced
aggregation
platelet
Other laboratory evaluations in the patient with hemophilia include periodic screening for the
Bleeding episodes are treated with factor VIII or factor IX (plasma-derived or recombinant)
replacement therapy and spontaneous bleeding is usually controlled if the patients factor VIII or factor
IX level is raised above 20% of normal. For major surgery, serious post-traumatic bleeding or when
hemorrhage is occurring at a dangerous site, however, the factor VIII level should be elevated to
100% and then maintained above 50% when acute bleeding has stopped, until healing has occurred
(Table 3).
Replacement Therapy
Table 3. Replacement Therapy for Hemorrhage in Hemophilia A and B
Joint
Required Factor Level

(%)
30-50
60-100 U/k/d
30-40 U/kg q2d
Muscle
40-50
20-40 U/kg/d
40-60 U/kg q2d
Oral mucosa
50, add EACA
25 U/kg
50 U/kg
Epistaxis
80-100, then 30 until

healed
40-50 U/kg, then 30-40

U/kg/d
80-100 U/kg, then 70-80

U/kg q2d
GI tract
100, then 30 until

healed
40-50 U/kg, then 30-40

U/kg
80-100 U/kg, then 70-80

U/kg q2d
Genitourinary tract
100, then 30 until

healed
40-50 U/kg, then 30-40

U/kg/d
80-100 U/kg, then 70-80

U/kg q2d
CNS
100, then 50-100 for

10-14 d
50 U/kg, then 25 U/kg

q12h or continuous
infusion
100 U/kg, then 50 U/kg/d
Trauma or surgical
site
100, then 30-50 until

healed
50 U/kg, then q12h or

continuous infusion
100 U/kg, then qd
Site of Bleeding
Dose in Hemophilia A
Dose in Hemophilia B
Desmopressin vasopressin analog, or 1-deamino-8-D-arginine vasopressin (DDAVP) is

considered the treatment of choice for mild and moderate hemophilia A. It is not effective in the
Replacement Therapy
Prophylactic
Gene Therapy
Inhibitor?
Vitamin K Deficiency
Bleeding
Vitamin K Deficiency
Bleeding
Hemorrhagic
disease of newborn (HDN) = vitamin K

deficiency bleeding (VKDB)
VKDB is bleeding due to inadequate activities of VK-dependent
coagulation factors (II, VII, IX, X), correctable by VK
replacement.
The frequency of VKDB varies with the use of vitamin K
prophylaxis, the efficacy of prophylaxis programs, frequency
of breastfeeding, and the vitamin K content of locally
available formulas
Late VKDB has fallen from 4.4-7.2/100,000 births to 1.46.4/100,000 births in reports from Asia and Europe after
regimens for prophylaxis were instituted
Intracranial hemorrhage (ICH) is uncommon in classic VKDB
but can be observed in more than 50% of infants with lateonset VKDB
VKDB: Pathophysiology
Vitamin
K is a fat-soluble vitamin
that can be absorbed from the GI
tract in the presence of bile salts
is required for the production of
coagulation factors II, VII, IX, and X
in the liver
Short
half-life of these factors, and

the small amounts of vitamin K that
can be stored in the body,
Pathophysiology
Why does it happen?

Maternal
factor:
Inadequate intake
Not nursing long enough or frequently
enough
Medications taken during pregnancy
Maternal diabetes, toxemia, or placental
problems.
Undue stress during the pregnancy.
Why does it happen?

Newborn
factor
Poor feeding, or not nursing enough.

Gastro-intestinal disease or homeostasis (blockage
of bile drainage ducts in the liver, caused by

hepatitis, undeveloped bile ducts or other congenital
defects, or infection)
Medications that the mother has taken
A particularly difficult birth, resulting in birth trauma.
Prematurity
Hypoxia (lack of oxygen)
Diarrhea
mmediate investigation/treatment of warning bleeds, help prevent the worst consequences of VKDB;
oo often is VKDB the presenting feature of a serious underlying disease which could have been
ecognized earlier.
Classification
Table 1. Forms of VKDB in Infancy
DIAGNOSIS
Clinical Features
VKDB: Clinical Features

VKDB
includes bleeding at any site

and whether spontaneous or
iatrogenic
The common sites for spontaneous
bleeding are the umbilicus, mucous
membranes, skin, gastrointestinal
and urinary tract, and
retroperitoneum
Intracranial bleeding can occur
Laboratory findings
Prothrombin
time (PT), activated partial

thromboplastin time (aPTT), fibrinogen
levels, and a platelet count in the initial
workup for bleeding in a newborn
prolonged PT usually is the first laboratory

test result to be abnormal in VKDB
NO
laboratory test can confirm the

diagnosis of VKDB.
VKDB: treatment
Vitamin
K is the mainstay of
treatment for VKDB
Severe bleeding may warrant the
use of fresh frozen plasma
Surgery when needed
Prevention
Vitamin K after
birth
Diet and
supplementation
Breast feeding
Risks of Giving the Prophylactic

Vitamin K Shot to the Baby
Too
much Vitamin K may be harmful

to baby. Levels remain 1,000 times
higher in the blood for 3-4 days after
the shot
Jaundice
Bleeding may still occur
Anaphylactic shock
Trauma at injection site (pain,
swelling)
Conclusion
3
major factors affecting coagulation

Inherited and acquired
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Bleeding Disorder

autoimmune disorder characterized

ITP: Clinical Features

ITP: Clinical features

platelet count is usually 10-50 x

is one of the oldest described genetic

A is approximately 1 case per 5000 male

B occurs in 1 case per 25,000 male individuals and

forms of hemophilia are sex-linked coagulopathies because

individuals who carry the affected genes usually do not

A and hemophilia B are found in all ethnic and racial

Table 1. Correlation of Coagulation Factor Activity and Disease Severity in Hemophilia A

Table 2. Main Clinical and Laboratory Findings in Hemophilia A and Hemophilia B

Main site of hemorrhage

Muscle, joints, post-trauma or

Muscle, joints, post-trauma or

Partial thromboplastin time

Required Factor Level

30-40 U/kg q2d

40-60 U/kg q2d

50, add EACA

80-100, then 30 until

40-50 U/kg, then 30-40

80-100 U/kg, then 70-80

100, then 30 until

40-50 U/kg, then 30-40

80-100 U/kg, then 70-80

100, then 30 until

40-50 U/kg, then 30-40

80-100 U/kg, then 70-80

100, then 50-100 for

50 U/kg, then 25 U/kg

100 U/kg, then 50 U/kg/d

100, then 30-50 until

50 U/kg, then q12h or

100 U/kg, then qd

Desmopressin vasopressin analog, or 1-deamino-8-D-arginine vasopressin (DDAVP) is

disease of newborn (HDN) = vitamin K

half-life of these factors, and

Why does it happen?

Why does it happen?

Poor feeding, or not nursing enough.

of bile drainage ducts in the liver, caused by

Table 1. Forms of VKDB in Infancy

VKDB: Clinical Features

includes bleeding at any site

time (PT), activated partial

prolonged PT usually is the first laboratory

laboratory test can confirm the

Risks of Giving the Prophylactic

much Vitamin K may be harmful

major factors affecting coagulation

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