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PE26.6 | Idiopathic Thrombocytopenic Purpura — SDL Guide

Learning Objectives

• Describe the clinical features of immune thrombocytopenia (ITP) in children, including the characteristic presentation after a viral illness
• Explain the immune-mediated pathophysiology — anti-GPIIb/IIIa antibody production, splenic Fc-receptor-mediated platelet destruction, and impaired megakaryopoiesis
• Outline the diagnostic approach, including the critical distinction between ITP and acute leukaemia when hepatosplenomegaly is present
• Stratify management by severity: observation for mild disease, IVIG/anti-D/corticosteroids for moderate, and rescue therapy for life-threatening bleeding

INSTRUCTIONS

Immune thrombocytopenic purpura is the commonest cause of acute thrombocytopenia in a previously healthy child, and a paediatrician must be able to recognise it rapidly, distinguish it from sinister causes such as leukaemia, and decide whether treatment or observation is the appropriate course. The principles you learn here — platelet physiology, immune-mediated destruction, and severity-stratified care — recur across many haematological conditions you will encounter throughout your career.

References

• Ghai Essential Pediatrics, 9th ed., Ch. 16 (textbook)
• Nelson Textbook of Pediatrics, 21st ed., Ch. 504 (textbook)
• IAP guidelines on management of ITP in children, 2019 (guideline)

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Version 2.0 | NMC CBUC 2024

Clinical Presentation of ITP

Immune thrombocytopenic purpura in children presents with a characteristic clinical pattern that, when recognised, allows confident diagnosis at the bedside. The typical patient is a child between 2 and 8 years old who presents with the sudden appearance of petechiae, purpura, and bruising over the body — often noticed by parents overnight on the child's legs. Critically, the child is otherwise well: no fever, no pallor, no significant lymphadenopathy, and — most importantly — no hepatosplenomegaly. The presence of hepatosplenomegaly should immediately shift suspicion towards an infiltrative process such as acute lymphoblastic leukaemia, and this must be excluded before attributing thrombocytopenia to ITP alone. A history of a preceding viral illness (upper respiratory tract infection, varicella, viral gastroenteritis) 2–4 weeks before the onset of bruising is present in the majority of childhood ITP cases, and this temporal association is a key clue.

Provided image

The spectrum of bleeding in ITP ranges from trivial to severe. Most children have only skin manifestations — petechiae (pinpoint, <3 mm, non-blanching haemorrhages in the skin) and purpura (larger, 3–10 mm, also non-blanching). Ecchymoses (bruises, >1 cm) may also occur, often in unusual locations like the trunk, not just bony prominences. Mucosal bleeding such as gum bleeding and epistaxis is common with platelet counts below 20,000/µL. The most feared complication is intracranial haemorrhage (ICH), which occurs in <0.5% of cases and is more likely when platelets are <10,000/µL or with head trauma. Gastrointestinal bleeding can also occur with very low counts.

The clinical classification by duration is important for management planning:
• Newly diagnosed ITP: within 3 months of diagnosis
• Persistent ITP: 3–12 months duration
• Chronic ITP: >12 months duration (commoner in adults; uncommon in children, where >80% resolve within 6–12 months)

Pathophysiology and Aetiology

Understanding why platelets fall so dramatically in ITP requires appreciating the interplay between autoimmune antibody production, splenic macrophage activity, and impaired platelet production — three processes that all converge to produce severe thrombocytopenia. The central mechanism is the production of autoantibodies — primarily IgG antibodies directed against platelet surface glycoproteins, most commonly glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin αIIbβ3). This complex normally mediates platelet aggregation by binding fibrinogen; when it becomes the target of autoantibodies, the antibody-coated platelets are recognised as foreign by splenic macrophages.

The sequence of events is as follows. A preceding viral infection (e.g., Epstein-Barr virus, cytomegalovirus, varicella, or non-specific URTI) triggers an immune response. By a mechanism thought to involve molecular mimicry — in which viral antigens share structural similarity with platelet glycoproteins — B-lymphocytes begin producing anti-platelet IgG. These antibodies coat circulating platelets. Splenic macrophages express Fc-γ receptors that recognise the Fc region of the bound IgG; the antibody-coated platelets are thereby phagocytosed and destroyed in the spleen. The liver (Kupffer cells) contributes additionally. Simultaneously, the autoantibodies can bind to megakaryocytes in the bone marrow, impairing platelet production — so platelet destruction is compounded by reduced production.

Vaccination (especially MMR) has also been implicated in triggering ITP through a similar mechanism, though the absolute risk is far lower than that of vaccine-preventable diseases themselves. Secondary ITP — where the thrombocytopenia is caused by an underlying disease — can occur in systemic lupus erythematosus (SLE), HIV infection, antiphospholipid syndrome, and lymphoproliferative disorders; these must be excluded in atypical presentations.

Immune Thrombocytopenia: Platelet Destruction and Impaired Production

Diagnosis and Investigation

The diagnosis of ITP is a diagnosis of exclusion — there is no specific confirmatory test, and the clinician must systematically rule out other causes of thrombocytopenia before concluding that a child has ITP. The first and most critical investigation is the complete blood count (CBC). In ITP, the defining haematological pattern is isolated thrombocytopenia: a low platelet count with a normal haemoglobin, normal white cell count, and normal differential. Any abnormality in the non-platelet lineages — anaemia, leucopenia, or leucocytosis — must prompt a bone marrow examination to exclude leukaemia or aplastic anaemia. This single point is the most important differentiator between ITP and acute leukaemia at the bedside.

The peripheral blood smear is mandatory and provides essential information. In ITP, platelets are reduced in number but those present are often larger than normal (megathrombocytes), reflecting increased thrombopoietic drive in the marrow. Importantly, red cell morphology is normal (no fragments/schistocytes, which would suggest thrombotic thrombocytopenic purpura or haemolytic-uraemic syndrome), and blast cells are absent. The presence of blast cells on the smear is an absolute indication for bone marrow biopsy.

Bone marrow examination is NOT routinely required for typical childhood ITP (post-viral, isolated thrombocytopenia, well child). It is indicated in atypical presentations: when steroids are planned before the diagnosis is confirmed (steroids alone could mask leukaemia), when the CBC shows cytopenias beyond thrombocytopenia alone, when hepatosplenomegaly is present, when the child looks systemically unwell, or when the platelet count fails to respond to standard therapy. Additional tests to consider for secondary causes include ANA (for SLE), HIV serology in at-risk patients, and antiphospholipid antibody screen (for recurrent cases). Coagulation tests (PT, aPTT) are normal in ITP — platelet-type bleeding does not disturb coagulation pathway tests.

Investigation	Finding in ITP	Significance
CBC	Platelets ↓↓, Hb normal, WBC normal	Isolated thrombocytopenia
Peripheral smear	Reduced platelets, megathrombocytes; no blasts, no red cell fragments	Excludes TTP/HUS/leukaemia
Bone marrow (if indicated)	Megakaryocytes ↑ or normal, no blast infiltration	Excludes aplastic anaemia, leukaemia
PT/aPTT	Normal	Confirms platelet-type (not coagulation-type) bleeding
ANA, anti-dsDNA	Positive in SLE-related thrombocytopenia	Excludes secondary ITP
HIV serology	Positive in HIV-associated thrombocytopenia	Excludes secondary ITP

ITP versus ALL: Key Diagnostic Differences