Immune thrombocytopenia (ITP)

Etiology

• Children: Peak age 2–5 yo; often preceded by viral illness or live-attenuated vaccine (e.g., MMR). Usually acute and self-limiting (spontaneous resolution within 6 months). c
• Adults: Peak age 20–40 yo; female predominance (F > M). Often insidious onset and chronic (> 12 months).
• Secondary ITP associations:
  • Autoimmune: SLE, antiphospholipid syndrome.
  • Infectious: HIV, HCV, H. pylori.
  • Malignancy: CLL, lymphoma.

Pathophysiology

Antiplatelet antibodies (mostly IgG directed against, e.g., GpIIb/IIIa, GpIb/IX) bind to surface proteins on platelets → sequestration by spleen and liver → ↓ platelet count → bone marrow megakaryocytes and platelet production increase in response (in most cases).

Clinical features

• Mostly asymptomatic. Splenomegaly is very unusual in ITP and makes other diagnoses more likely!
  • Although platelets can undergo splenic sequestration in ITP, the primary mechanism responsible for the thrombocytopenia is immune destruction.

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Diagnostics

• Initial Test: CBC w/ Peripheral Blood Smear
  • Isolated thrombocytopenia (Plt often < 20,000–30,000/$\mu$L).
  • Normal Hb/Hct (unless secondary to heavy bleeding) and normal WBC count.
  • Smear: Megathrombocytes (large platelets); absence of schistocytes, blasts, or platelet clumping.
• Secondary Workup (Mandatory in all pts):
  • HIV and HCV testing (essential routine screening in all newly diagnosed adults).
  • Direct antiglobulin test (DAT/Coombs) if concurrent anemia (to rule out Evans syndrome).
  • ANA testing if features suggestive of SLE. c
• Confirmatory / Gold Standard:
  • Diagnosis of exclusion; no specific confirmatory laboratory test exists (anti-platelet Ab testing has poor sensitivity/specificity and is not recommended).
• Bone Marrow Biopsy:
  • Not routinely indicated.
  • Indicated only if: Atypical features (age > 60 yo, systemic symptoms, other cytopenias) or failure to respond to standard therapy.
  • Findings: Increased megakaryocytes with normal erythroid and myeloid precursors.

Differential diagnostics

Feature	Thrombotic Thrombocytopenic Purpura (TTP)	Immune Thrombocytopenia (ITP)
Patho	↓ ADAMTS13 activity → Large vWF multimers → microvascular platelet thrombi	Anti-platelet (anti-GpIIb/IIIa) Abs → splenic destruction of platelets
Presentation	Pentad (FAT RN): Fever, Anemia (MAHA), Thrombocytopenia, Renal failure, Neurologic sx (e.g., confusion, stroke). Often acutely ill.	Isolated mucocutaneous bleeding (petechiae, purpura, epistaxis). Often asymptomatic. No splenomegaly.
Labs	MAHA triad: Anemia, Thrombocytopenia, Schistocytes on smear. ↑LDH, ↑Bilirubin, ↓Haptoglobin. Normal PT/PTT. Dx confirmed by ADAMTS13 assay (<10%).	Isolated thrombocytopenia (<100,000/µL). Smear may show megathrombocytes. Otherwise normal CBC & smear. Normal PT/PTT. Dx of exclusion.
Tx	EMERGENT. Plasma exchange (PEX) is first-line & life-saving. Corticosteroids, Rituximab. Platelet transfusion is CONTRAINDICATED (fuels thrombosis).	1st line: Corticosteroids, IVIG. 2nd line: Splenectomy, Rituximab, TPO-RAs (e.g., romiplostim). Observe if plt >30k & no bleeding.

Management

• Children:
  • Skin-only bleeding (regardless of Plt count): Observation only (80% resolve spontaneously). c
  • Active mucosal bleeding: Corticosteroids OR IVIG.
• Adults:
  • Plt $\ge$ 30,000/$\mu$L & asymptomatic: Observation.
  • Plt < 30,000/$\mu$L OR significant bleeding:
    • First-line: Corticosteroids (Dexamethasone or Prednisone).
    • Adjunct/Rapid rise: Add IVIG or Anti-D.
  • Life-threatening bleeding (e.g., ICH): Platelet transfusion + IV Methylprednisolone + IVIG.
  • Refractory / Chronic:
    • TPO receptor agonists (Eltrombopag, Romiplostim).
    • Rituximab (anti-CD20).
    • Splenectomy (vaccinate $\ge$ 14 d prior). c