Approach to a Case of

Bleeding Disorder

Introduction
Challenge of the Pediatrician in evaluating a
child with a potential bleeding disorder is to
ascertain whether the patients symptoms are
appropriate to the hemostatic stress or
whether further investigations of an
underlying
hemorrhagic
disorder
is
warranted.
Gone are the days of simply pass the FFP, if
somethings missing its bound to be in here.

Hemostasis
Physiological cessation of bleeding:
PRIMARY HEMOSTASIS: Production of
platelet plugs
SECONDARY HEMOSTASIS: Formation
of cross linked fibrin clots.
Regulated by fibrinolytic system and
anticoagulants (Protein C,S, antithrombin III,
platelet inhibitors, prostacyclin)

Platelet adhesion and aggregatio

Abnormal Bleeding
Epistaxis not relieved by 15 minutes of
pressure along the entire site of the nose.
Menstrual period lasting longer than 7
days or associated with passage of clots.
Bleeding from dental procedure lasting
beyond the day of procedure or requiring
blood transfusion.
Ecchymosis of a size or character
inconsistent with the degree of trauma.

History
Clues to a congenital bleeding disorder
1. Questioning
regarding
excessive
bleeding/bleeding disorder after dental
extraction, tonsillectomy or umbilical
stump bleeding
2. Hemophilia (A/B) is suggested when a
toddler who starts walking comes with
bruising and painful swollen joints
3. A history of bleeding disorder in family
member.

 Clues to an acquired bleeding disorder

Apparent well looking child presenting with
petechiae and ecchymosis with history of
preceding viral infection. e.g. ITP, HUS.
Nature of bleeding
1. Sites of bleeding

Mucous membrane bleeding and petechiae are

often seen in platelet related disorders
Soft tissues hematomas, bleeding in joints
without petechiae or mucous membrane
bleeding suggest a defect in the coagulation
cascade.

2. Severity of bleeding
Spontaneous bleeding in severe disorder.
Bleeding after major trauma/surgery suggest
mild bleeding

3. Timing of Episodes
Bleeding uncontrolled from the onset
suggests a defect in primary hemostasis.
History of bleeding after initial apparent
hemostasis is more consistent with a factor
deficiency.

4. Medical history
Malnourished, hospitalized patient with
multiple antibiotics prone for Vitamin K
deficiency
SLE, viral infection and HIV infection are
associated with ITP
Septicemia, shock, incompatible blood
transfusion are associated with DIC

5. Medication
Aspirin: altered platelet function
Drugs: induce thrombocytopenia
Penicillin: factors inhibitors

Physical Examination
1. Petechiae: bleeding at the level
microvasculature and abnormalities
platelet number and function.

of
of

2. Mucous membrane bleeding

Coagulation defect
When mucous membrane are the only
bleeding
sites,
platelet
dysfunction,
thrombocytopenia and von Willebrands
diseases is likely

3. Hemarthrosis, bleeding in facial planes

in severe form of hemophilia
4. Diffuse bleeding from multiple sites both
mucous membrane and sites of trauma
such as venipuncture if often seen in
severe coagulation defects like DIC or
severe liver diseases.
5. Supportive Evidence like splenomegaly,
lymphadenopathy, sepsis

Clinical Clues to differentiate between Platelet Disorder

and Coagulation Disorder
Findings

Bleeding due to
Bleeding due
Platelet and
to Coagulation
Vascular disease

Petechiae

Positive

Negative

Hemarthrosis

Negative

Positive

Ecchymosis/Hematomas Negative

Positive

Onset of bleeding after

trauma

Immediate

Delayed

Sex distribution

Female > Male

90% Male

Family history

Rarely positive

Commonly
positive

Laboratory Studies
PLATELET TEST:
1. CBC with absolute platelet count
Determines primary hemostasis defect
Thrombocytopenia, leukopenia, anemia
suggestive of bone marrow failure

2. General blood picture for platelet count

and platelet morphology
3. PFA (Platelet Function Assessment)- 100
platelet function screen

 Automated device that aspirates small

amount of citrated blood and aperture in a
membrane is coated with collagen and either
epinephrine or adenosine diphosphate (ADP)
The exposure to platelet agonists
Adhesion and aggregation
Occlusion of aperture by platelet plug
Occlusion time is noted

4. Platelet function

Bleeding time: Crude test

Platelet aggregation
Aggregation with ADP, epinephrine or collagen
Uncovers
abnormalities
of
fibrinogen
binding
(thrombasthenia) or of Arachidonic acid metabolism
(Aspirin)
Aggregation with ristocetin is abnormal in von
Willedrands diseases and in Bernard Soulier disease

Platelet Function Defect

Von Willebrand receptor = GP Ib
Fibrinogen receptor = GP IIb IIIa complex

Bernard Soulier syndrome

Autosomal recessive disorder
Normal vWF but decrease/absent GP Ib
receptor
Normal platelet aggregation with all agonists
but no aggregation with ristocetin, i.e.
ristocetin is required for vWF to bind to
platelet via GP Ib receptor

 GP Ib complex is required for cytoskeleton

structure maintenance of platelet whose
absence cause giant platelet
Glanzmann Thrombasthenia
Autosomal recessive disorder
Deficiency of GP IIb IIIa complex which is
required for conformational changes when
platelet is activated and fibrinogen binds to
this for platelet to aggregate.
Normal platelet aggregation with ristocetin
but abnormalities with other agonist
Normal platelet morphology

Immune Thrombocytopenic Purpura

Autoantibodies are produced against the
platelet. These complex are recognized by
the Fc receptor on the splenic macrophages
and destroyed.
Clinical Features
Preceding history of viral infection 3 4 weeks
back
Petechiae, purpura,
splenomegaly < 1%.

epistaxis,

hematuria,

 Clinical course
60% - complete remission in 1st month
80 - 90% resolve by 6 month after diagnosis
10% become chronic
< 1 % intracranial hemorrhage

Incidence
Peaks during winter
Acute ITP refers to thrombocytopenia lasting
for< 6 month and chronic ITP > 6 month

Difference between Acute ITP and Chronic ITP

Features

Acute ITP

Chronic ITP

Peak age incidence

2 6 years

20 40 years

Sex predilection

None

3 : 1 (F : M)

Antecedent infection 1 3 wk before (84%) Unusual

Onset of bleeding

Abrupt

Insidious

Hemorrhagic bulla in Present in severe

mouth
cases

Absent

Platelet count

< 20000/mm3

30 - 80000/mm3

Eosinophilia and
lymphocytosis

Common

Rare

Duration

2 6 weeks

Months to year

Spont. Remission

In 80% cases

Uncommon

 Investigation
Hemoglobin Anemia is proportionate to the
degree of bleeding
APC decreased
PT/APTT normal
Bone marrow megakaryocytes are normal
or increased, shows decreased budding and
intense blue cytoplasm.
Antiplatelet antibodies

Treatment
Corticosteroids
Mechanism of action
Increase vascular stability and ameliorate the
endothelial abnormalities
Decreased production of anti platelet
antibodies from spleen and bone marrow
Decreased destruction of platelet in spleen
and bone marrow
Increased marrow platelet production

 Dose schedule
Oral Prednisolone 2 mg/kg/d or (60mg/m2/d) for
21 days
Oral Prednisolone 4 mg/kg/d for 7 days and
then tapered over 21 days.
IV Methylprednisolone 30 mg/kg/d for 3 days

Intravenous Immunoglobulin

Mechanism of action
Occupation of Fc receptor on
reticuloendothelial cells resulting in survival
of antibody coated platelets
Binding to circulating antibodies and
rendering them ineffective
Suppress B cells auto antibody production

Dose schedule
1 g/kg or 0.8 g/kg single dose
0.4 g/kg/d for 2 days

Anti Rh (D)
Mechanism of action
Blockade of Fc receptor

Dose schedule
25 g/kg/d for 3 days

Vinca alkaloids
Vinblastine 0.1 mg/kg or Vincristine 0.02
mg/kg every weekly for 4 weeks
Danazol
300 400 mg/m2/d orally for 2 3 months
Presumably decreases Fc receptor

Splenectomy
Children where thrombocytopenia persisted
for more than 1 year with clinically important
bleeding
Persistence of disease for more than 1 year
with bleeding symptoms; platelet count <
10,000 without bleeding;10 - 30,000 with
bleeding symptoms.

Mechanism
Spleen is a major site of antibody production
Major site of clearance of antibody coated
platelet