Thrombocytopenia

in Children
Endang Windiastuti
Division of Hematology-Oncology
Department of Child Health
Dr Cipto Mangunkusumo Hospital,
Faculty of Medicine, University of Indonesia

Objective
Recognize stratifying levels of thrombocytopenia
Formulate differential of children with
thrombocytopenia
Manage thrombocytopenia.
Plan management of ITP.

Structure of thrombocyte, von Willebrand factor

Membantu
perlekatan
Reseptor
interaksi dg
dinding p darah

Membrane (aktivasi Fibrin)

Trombosit

Hemostasis
Platelets adhere to site of
vascular injury

Platelets aggregation and

activation

Haemostatic plug
formation

Risk of Bleeding

Desk Reference for Hematology, 2nd ed, 2008

PDQ Hematology, 2002

Practical Aspects for the management of

thrombocytopenia
What is an adequate platelet count for
procedures?

Routine Dentistry >10.000/ul

Dental Extraction >30.000/ul
Regional Dental Block >30.000/ul
Minor Surgery >50.000/ul
Major Surgery>80.000/ul

The target platelet count for a bleeding patient is

generally >40.000/ul
Prophylactic platelet transfusions for platelets <
10.000/ul
British Hematology Task
Force Recommendations

Mechanisms of Thrombocytopenia
1)
2)
3)
4)

Decreased platelet production

Increased platelet destruction
Splenomegaly or splenic sequestration
Pseudothrombocytopenia

1. Decreased Platelet Production

Bone marrow suppression or damage

Viral illness
HIV (direct damage to Megakaryocytes)
Chemo- or radiation therapy
Congenital or acquired bone marrow aplasia or
hypoplasia

2. Increased Platelet Destruction

Immune Thrombocytopenic Purpura
Alloimmune destructionPost-transfusion, Posttransplantation
Disseminated Intravascular Coagulation/DIC
Thrombotic Thrombocytopenic Purpura
Antiphospholipid Antibody Syndrome
Certain drugsHeparin, quinidine, valproate

Splenic Sequestration
(Abnormal distribution)
Normally, ~1/3 of platelets are sequestered in the spleen
In extreme splenomegaly, up to 90% of platelets can be
trapped in the spleen
Hypersplenism
Up to 90% sequestered
May occur in a wide variety of diseases
Infection
Inflammation
Hematologic diseases
Neoplasm

Pseudothrombocytopenia
Platelet clumping seen with EDTA but
not with citrate or heparin no known
consequence

Incidence of ITP

Williams Hematology 2005, Beutler et al.

Etiology of ITP : Children

Often after infection (viral or bacterial)
Theories:
*antibody cross-reactivity
*H. pylori (platelets aggregation)
*bacterial lipopolysaccharides (adhered to
platelets)

Initial Approach
Bleeding History
Drug Ingestion
CBC and peripheral smeargold
standard
Immune Thrombocytopenic Purpura (ITP)
is a Diagnosis of exclusion when
Anamnesis & P.E.,Drug ingestion,CBC,
and peripheral smear do not suggest other
etiologies

Diagnosis (of Exclusion)

Rule out other causes:

lab error / PLT clumping

drug / medication interaction
infections (HIV, Hepatitis C)
thyroid / autoimmune disease
destructive / consumptive processes (HUS)
bone marrow disease (leukemia, MDS)

Medications
The Main Offenders
Valproic acid/Carbamazepine
Amphotericin B
Quinine/quinidine
Cimetidine
Sulfonamides
Penicillin/Beta lactams
Interferon
Ranititidine

Vancomycin
Phenytoin
Digoxin
Fluconazole

Platelet-inhibitory drugs:
duration of bleeding risk
Drugs

Platelets effects

Duration of
increased
bleeding risk

Aspirin

Irreversible

5 days

Ibuprofen

Reversible

24 hours

Naproxen

Reversible

Up to 4 days

Thienopyrydine

Irreversible

7 days

Dipyridamole

Reversible

Minimal to no risk

ASH Educational Book, Dec 2011

Pathogenesis of ITP
Increased platelet destruction caused by
antiplatelet antibodies
Autoantibodies (usually IgG) directed against
platelet membrane antigens
Phagocytosis of antibody-coated platelets by the
reticuloendothelial system .
Lack of compensatory response by
megakaryocytes due to suppressive effect of
antiplatelet antibodies

Antibody

Platelets

Antigen

Pathogenesis
Antigen-antibody
complexes

Sensitized Platelets

Sensitized Platelets

Spleen
Fc receptor

Macrophage
Increased bone marrow
production of
megakaryocytes

Thrombocytopenia
TPO

Evaluation of ITP
Features consistent with the diagnosis of ITP
Thrombocytopenia with normal or slightly large
platelets
Normal RBC / WBC morphology and number
Splenomegaly rare

Features not consistent with the diagnosis of ITP

RBC abnormalities ie schisotocytes
Leukocytosis or Leukopenia

LABORATORY EXAMINATION

For the typical case of ITP :

CBC
Platelet count
Peripheral blood smear

For the atypical case of ITP :

Viral antibody titers (including HIV-1)

Coombs test
Reticulocyte count
Studies for collagen vascular and rheumatoid
disorders

DIFFERENTIAL DIAGNOSIS
1. Active infection (eg, infectious mononucleosis,
hepatitis, HIV-1)

2. Drug exposure (eg, heparin, quinidine, sulfonamides )

3. Autoimmune disease (SLE)
4. Leukemia ( ALL )

5. Acquired bone marrow failure syndromes (eg, aplastic

anemia)

Classification
Acute ITP
Mostly children
Male/Female ratio 1:1
Acute onset

Thrombocyte <20.000 mm3

Spontaneous remission
frequent

Mortality : 0.5 1.5%

Chronic ITP
Mostly adults
Male /Female ratio 1 : 3-4
Usually gradual onset
Thrombocyte 20.000-50.000/mm3
Sponatneous remision rare
Chronic recurrent course.

24

Common Signs and Symptoms

Abrupt onset
(acute ITP)

Epitaxis
Gingival bleeding

Gradual onset
(Chronic ITP)
Purpura
Menorrhagia

Recent virus immunization

(acute ITP)
Recent viral illness (acute ITP)
Bruising tendency

25

Common Physical Findings

Nonpalpable petechiae
Hemorrhage
Purpura
Gingival bleeding
Signs of GI bleeding

Spontaneous bleeding (
thrombocyte 10.000/mm3

Menorrhagia
Retinal hemorrhage
Evidence of
intracranial
hemorrhage
Nonpalpable spleen

26

..clinical manifestasion

Management of ITP
Most patients with ITP do not have clinically significant
bleeding
Risk of intracranial bleed 0.1 to 1%
Wet Purpura (epistaxis, gingival bleeding) is a risk factor for
major bleeding

In asymptomatic patients with platelets > 20.000/mm3

observation
The principal management goal in all patients who have
thrombocytopenia is to maintain a safe platelet count to
prevent significant bleeding, not to achieve a normal
platelet count.

management
Drugs

Cortikosteroid

Dosage

Meshanism

Prednison :
-2 mg/kg/day (max 60-80
mg) for 21 days
-4 mg/kg/day for 7 days
tappered to day 21
-4 mg/kg/day for 4 days

-Inhibition

Methylprednisolone :
30 mg/kg/day IV or oral for
3 days

phagocytosis and Ab
synthesis
-Improved platelet production
-Increased microvascular endothelial
stability
-Impairing the ability of macrophages
in bone marrow to destroy platelet
-Inhibit expression of certain Fc receptor
impending platelet clearance
-Inhibit Ab production

IVIG

1-2 g/kg divided over 2-5 d

or
250 mg/kg/day for 2 days

Inhibiting phagocytic activity of RES by

blocking Fc receptor

Anti-D

50-75 ug/kg IV

Phagocytic cell blockade

Nathan Orkins 2003
NEJM 2002;346:995-1008
J Pediatr Hematol Oncol 1997;19:197-201
Pediatric hematology.3rd ed, 2006

Bone marrow in ITP

Controversial
Indications:

Pediatrics in Review 2000;21:95-104

NEJM 2002;346:995-1008
NEJM 2002;346:995-1008
Pediatr Clin N Am 2008;55:393-420

Organomegaly
Bi or pansitopenia
Abnormal morphology
Hemoglobin , not equal with degree of bleeding
Bone pain or paresis
Before initial corticosteroid

NEJM 2002;346:995-1008
Pediatr Clin N Am 2008;55:393-420

Should the Patient be Hospitalized?

ITP Practice Guideline ASH

Patients with platelet counts >20,000 should
not be hospitalized if they are either
asymptomatic or have only minor purpura.
Hospitalization is appropriate for patients with
platelet counts <20,000 who have significant
mucous membrane bleeding.

Treatment guideline
ASH Guideline
Patients with counts >50,000 do not routinely
require treatment
Treatment is indicated
Platelet counts <20,000 to 30,000, and those with
Platelet counts <50,000 and significant mucous
membrane bleeding
Platelet count <50,000 with risk factors for
bleeding, such as hypertension, peptic ulcer
disease.

Treatment & Prognosis

Acute ITP
Self remission 80%
Corticosteroid therapy within 3-4 weeks
No response to corticosteroid > 6 months (15 %)
consider Splenectomy
10 % will recover normal platelet levels in the next
few months
15 to 20 % will have a clinically important moderate
or major hemorrhagic problem
Life-threatening bleeding, including ICH, is rare,
occurring with an incidence of 0.1 to 1 %
33

Summary
Thrombocytopenia should be suspected in any child
presenting with a history of easy bruising or bleeding or
petechiae
The diagnosis of ITP can be made using two criteria:
1) isolated thrombocytopenia with otherwise normal blood
counts and peripheral blood smear and
2) no clinically apparent associated conditions that may cause
thrombocytopenia.

Pharmacologic intervention, including corticosteroids,

IGIV, has been shown to raise the platelet count more
quickly than no therapy and is recommended for children
who have or at risk for severe or life-threatening
bleeding, based on strong evidence

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