BLEEDING (PLATELET) DISORDER
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APPROACH
The initial set of questions should establish the
following:
(1) the most common site and type of bleeding (e.g.,
mucocutaneous versus articular or deep muscle),
(2) bleeding on hemostatic challenge such as surgeries
or trauma, and
(3) family history of bleeding.
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Clinical Primary Hemostatic Clotting Factor
Characteristic Defect Deficiency
Site of bleeding Skin, mucous Soft tissues, muscles,
membranes joints
Bleeding after Yes Rare
minor cuts
Petechiae present absent
Ecchymosis Small, superficial Large, deep,
palpable
Hemarthrosis Rare Common
Bleeding after Immediate Delayed
trauma/surgery
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PLATELET IN VASCULAR INJURY
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HISTORY
Large bruises without previous significant trauma,
disseminated petechiae,intramuscular hematomas,
hemarthrosis (joint effusion, warmth, and pain with
passive movement) usually indicate a bleeding
disorder
In young children, refusal to walk is often a sign for
an extremity-related bleed and could represent the
first sign of hemarthrosis in a boy with hemophilia
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HISTORY
Symptoms of bleeding disorders, could be easy bruising and
mucosal bleeding(e.g. Epistaxis,menorrhagia,oropharyngeal)
Inflicted trauma is most likely to manifest over the head,
chest, back, and long bones (and may retain the outlines of
the instrument used to inflict harm), whereas bruises
associated with primary hemostasis defects are usually
located over areas of typical childhood trauma, such as bony
protuberances of extremities or spinous processes
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HISTORY
Epistaxis is a frequent presenting sign in children
with hemostatic disorders
Epistaxis is also a common complaint among healthy
children, usually the result of local aggravating
factors (dry nasal mucosa, trauma, allergic rhinitis).
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HISTORY
Menorrhagia is also a frequent presenting sign for mild or
moderate bleeding disorders (including VWD, platelet
function disorders, and other coagulopathies) and can quickly
lead to severe anaemia and decreased quality of life.
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HISTORY
Profuse bleeding into soft tissues or joints suggests
deficiency of a coagulation factor (such as factors VIII
or IX).
Umbilical stump bleeding is typically seen with
factor XIII deficiency, but it may also occur with
deficiencies of prothrombin, factor X, and fibrinogen
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HISTORY
The main categories to be considered should include
anatomic abnormalities, quantitative and qualitative
platelet defects affecting platelet plug formation
(primary hemostasis), and quantitative and
qualitative defects of clot propagation (secondary
hemostasis).
Differentiation also must be made between inherited
and acquired disorders.
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HISTORY
• Information about the patient’s previous response to
hemostatic challenges (e.g., surgical procedures,
invasive dental work, traumatic injuries) is an
essential part of the initial evaluation
• Family history is also a key component in establishing
both the likelihood of an inherited bleeding disorder
and its specific nature.
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The three phases of coagulation occur on different cell
surfaces: initiation on the tissue-factor bearing-cell;
amplification on the platelet as it becomes activated;
and propagation on the activated platelet surface
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HISTORY
A sick child with fever, shock, and mucocutaneous
purpura may have disseminated intravascular
coagulation (DIC) associated with bacteremia.
Hemophilia should be considered in a male toddler
who has just started crawling and exhibits
subcutaneous or joint bleeding, or who bleeds after
circumcision.
A girl who has had severe menorrhagia since
menarche may have VWD.
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HISTORY
A well-appearing child covered with petechiae likely
has immune thrombocytopenia, but if the lesions are
localized to the buttocks, ankles, and feet, and they
present as palpable bruises, Henoch-Schönlein
purpura should be considered
The prevalence of bleeding disorders in women with
menorrhagia is as high as 20%, and menorrhagia is a
common initial symptom in women with VWD
(approximately 90% of female patients)
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HISTORY
Medical disorder that may affect hemostasis, hepatic
or renal disease, Malabsorption syndrome, or
Ehlers-Danlos syndrome (EDS) or another connective
tissue disorder.
Generally, early age of onset correlates with more
severe bleeding and may indicate a congenital cause.
Bleeding that develops later in childhood may
indicate either an acquired problem or a milder
congenital bleeding disorder
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HISTORY
An X-linked recessive inheritance pattern (maternal
cousins, uncles, and grandfather) suggests a
diagnosis of hemophilia A or B,
Autosomal dominant pattern would be more
consistent with VWD or hereditary haemorrhagic
telangiectasia.
Most other clinically relevant clotting factor
deficiencies are inherited in an autosomal recessive
manner
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HISTORY
A number of drugs can cause thrombocytopenia
(e.g., quinine or quinidine, rifampin, trimethoprim-
sulfamethoxazole, carbamazepine, cimetidine,
ranitidine, valproic acid)
platelet dysfunction (nonsteroidal anti inflammatory
drugs [NSAIDs] such as ibuprofen [reversible effect]
and aspirin [irreversible]).
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PHYSICAL EXAMINATION
Signs of severe bleeding-related anaemia or
intravascular volume loss, such as tachycardia (early
finding) or hypotension (late finding).
observe the pattern of bleeding stigmata
the presence of petechiae indicates a defect in
primary hemostasis (platelet number or function or
vascular integrity).
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PHYSICAL EXAMINATION
Ecchymoses are palpable purplish lesions induced by
subcutaneous bleeding and usually indicate a defect
in secondary hemostasis (clot propagation), such as
deficiency of a coagulation factor
Hemarthrosis, associated with severe coagulation
factor deficiency
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PHYSICAL EXAMINATION
Hepatomegaly and splenic enlargement may point
toward coagulopathy associated with systemic
disorders such as leukaemia or hepatocellular
disease.
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LAB
Complete blood count with evaluation of platelet
number, size, morphology, PT, APTT, and thrombin
time (TT) to help in the process of differential
diagnosis
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LAB
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LAB
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PLATELETS
Size: 1-4 μm (younger platelets are larger).
Distribution: one-third in the spleen, two-thirds in
circulation
Average lifespan: 9-10 days
Platelets critical component for the first phase of
hemostasis (formation of the platelet plug), which
can halt the loss of blood from vessels whose
endothelial integrity has been interrupted
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PLATELETS
Typically involve the skin or mucous membranes and
include petechiae, ecchymosis, epistaxis,
menorrhagia, and gastrointestinal hemorrhage.
Intracranial bleeding can occur, but it is infrequent
Inherited platelet disorders can involve a qualitative
and/or quantitative defect and are often broadly
classified according to one of these two categories
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BERNAD SOULIER SYNDROME
Bernard-Soulier syndrome, a severe congenital
platelet function disorder, is caused by absence or
severe deficiency of the VWF receptor (GPIb complex)
on the platelet membrane.
Thrombocytopenia, with giant platelets and
markedly prolonged bleeding time (>20 min) or PFA-
100 closure time.
Platelet aggregation tests show absent ristocetin-
induced platelet aggregation, but normal
aggregation to all other agonists.
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GLANZMANN THROMBASTHENIA
Glanzmann thrombasthenia is a congenital disorder
associated with severe platelet dysfunction that
yields prolonged bleeding time and a normal platelet
count.
Platelets have normal size and morphologic features
on the peripheral blood smear, and closure times for
PFA-100 or bleeding time are markedly abnormal
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GLANZMANN THROMBASTHENIA
This disorder is caused by deficiency of the
platelet fibrinogen receptor αIIb-β3, the major
integrin complex on the platelet surface that
undergoes conformational changes by inside out
signalling when platelets are activated
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• Dense body deficiency is characterized by absence of the
granules that contain ADP, ATP, Ca2+, and serotonin. This
disorder is diagnosed by the finding that ATP is not released
on platelet aggregation studies and ideally is characterized by
electron microscopic studies.
• Gray platelet syndrome is caused by the absence of platelet α
granules, resulting in platelets that appear gray on Wright
stain of peripheral blood. In this rare syndrome, aggregation
and release are absent with most agonists other than
thrombin and ristocetin.
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For both Bernard-Soulier syndrome and Glanzmann thrombasthen
diagnosis is confirmed by flow cytometric analysis of the patient's platelet
glycoproteins.
For individuals with Bernard-Soulier syndrome or Glanzmann
thrombasthenia, platelet transfusions of 1 U/5-10 kg corrects the defect in
hemostasis and may be lifesaving.
Desmopressin 0.3 µg/kg IV may be used for mild to moderate bleeding
episodes.
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WISKOTT ALDRICH SYNDROME
This syndrome has X-linked inheritance and has the
classic features of thrombocytopenia, eczema,
recurrent bacterial and viral infections
WAS has abnormal T cell function and a propensity
to develop autoimmune disorders
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WISKOTT ALDRICH SYNDROME
Recurrent pyogenic infections, including otitis media,
pneumonia and skin infections. There is also lowered
resistance to nonbacterial infections, including
herpes simplex and Pneumocystis jiroveci (formerly
carinii) pneumonia
Thrombocytopenia (platelet count
10,000-100,000/mm3); microthrombocytes; low
mean platelet volume (MPV).
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CAMT
Congenital Amegakaryocytic Thrombocytopenia
(CAMT) is a bone marrow failure syndrome that
presents with isolated thrombocytopenia in the
neonatal period. Inheritance is autosomal
recessive.
The most common age at diagnosis of the
thrombocytopenia is within the first month, because
ofpetechiae and other
The diagnosis bleeding
of CAMT, symptoms.
however, is not usually
made until the infant is several weeks or months old
when the bone marrow is examined.
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TYPE 2 b VWD
Type 2B von Willebrand Disease. Type 2B VWD is due
to a mutant VWF molecule that binds spontaneously
to platelets under physiologic shear.
This results in clearance of the highest-molecular-
weight multimers and usually mild
thrombocytopenia
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ITP
Immune thrombocytopenia is a disorder caused by
antiplatelet antibodies which lead to an accelerated
destruction of platelets and an inhibition of the production of
platelets.
ITP is the most common cause of thrombocytopenia in
children.
Peak occurrence is between 2 and 5 years of age.
In most children the disease is self-limited, with resolution in
80% of patients within 6-12 months from diagnosis
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ITP
Antibody-mediated destruction:
Most of the identified autoantibodies are directed
against GPIIb-GPIIIa, GPIb-GPIX and GPIa-Iia
Impaired megakaryopoiesis
Antibody and cellular cytotoxicity and immune-cell-
derived cytokines have been implicated in impairment
of megakaryocytes
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CLINICAL FEATURES
Typically patients are otherwise well and present
with petechiae, purpura and no palpable ecchymosis
1-3 weeks after a viral infection.
It may also occur after rubella, rubeola, chickenpox
or live virus vaccination.
Occasionally patients may present with mucosal
bleeding (hematuria, hematochezia,
Menometrorrhagia, or epistaxis).
Most often, bleeding symptoms are mild, but rarely
patients may develop severe bleeding including
intracranial hemorrhage
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American Society of Hematology (ASH)
DEFINITIONS
Primary ITP was defined by the IWG as a platelet count less
than 100 X 10 9/L
The IWG also defines ITP as newly diagnosed (diagnosis to 3
months), persistent (3 to 12 months from diagnosis), or
chronic (lasting for more than 12 months).
Complete response (CR) :A platelet count 100 X 10 9 /L
measured on 2 occasions 7 days apart and the absence of
bleeding.
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ASH DEFINITIONS
Response (R) :A platelet count 30 X 10 9/L and a greater than
2-fold increase in platelet count from baseline measured on 2
occasions 7 days apart and the absence of bleeding
No response (NR) :A platelet count 30 X 10 9/L or a less than
2-fold increase in platelet count from baseline or the
presence of bleeding. Platelet count must be measured on 2
occasions more than a day apart.
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Blood smear and bone marrow aspirate from a child who
had ITP showing large platelets (blood smear [left]) and
increased numbers of megakaryocytes, many of which
appear immature (bone marrow aspirate
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TREATMENT
No therapy other than education and counselling of the
family and patient for patients
“A single dose of IVIG [intravenous immunoglobulin] (0.8-1.0
g/kg) 1-2 days
Prednisone. Doses of prednisone of 1-4 mg/kg/24 hr appear
to induce a more rapid rise in platelet count than in untreated
patients with ITP
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TREATMENT
Intravenous anti-D therapy. For Rh-positive patients, IV anti-D
at a dose of 50-75 μg/kg causes a rise in platelet count to
>20 × 109/L in 80-90% of patients within 48-72 hr
The role of splenectomy in ITP should be reserved for 1 of 2
circumstances.
The older child (≥4 yr) with severe ITP that has lasted >1 yr
(chronic ITP) and whose symptoms are not easily controlled
with therapy is a candidate for splenectomy
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ASH GUIDELINES
Bone marrow examination is unnecessary in children
and adolescents with the typical features of ITP
(grade 1B).
Bone marrow examination is not necessary in
children who fail IV Ig therapy (grade 1B).
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Thank You
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