Immune Thrombocytopenia (ITP)

Diagnosis of exclusion, first-line corticosteroids and IVIG, and second-line thrombopoietin receptor agonists, rituximab, and fostamatinib for isolated immune-mediated thrombocytopenia

Key Points

• ITP is a diagnosis of exclusion: isolated thrombocytopenia (platelets <100 × 10⁹/L) with an otherwise normal CBC and smear, and no other identifiable cause. There is no confirmatory test.
• Treatment is driven by bleeding risk and platelet count — not the count alone. Many adults with platelets >30 × 10⁹/L and no bleeding can be observed without treatment.
• First-line therapy is corticosteroids (prednisone or high-dose dexamethasone); IVIG or anti-D is added when a rapid rise is needed for active bleeding or before a procedure.
• Thrombopoietin receptor agonists (TPO-RAs) — eltrombopag, romiplostim, and avatrombopag — are highly effective second-line agents that stimulate platelet production rather than suppress destruction.
• Rituximab and the splenic tyrosine kinase inhibitor fostamatinib are additional second-line options; splenectomy remains the most durable treatment but is used later given the efficacy of medical therapy.
• Always exclude secondary ITP — HIV, hepatitis C, H. pylori, SLE, common variable immunodeficiency, lymphoproliferative disorders, and drug-induced thrombocytopenia — because treating the cause can resolve the thrombocytopenia.

Pathophysiology and Definitions

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by immune-mediated destruction of platelets and impaired platelet production. Autoantibodies — most commonly directed against platelet glycoprotein IIb/IIIa or Ib/IX — opsonize platelets, which are then cleared prematurely by splenic (and hepatic) macrophages via Fcγ receptors. A second, equally important mechanism is impaired megakaryocyte function and platelet production: the same autoantibodies and cytotoxic T cells suppress megakaryocytes, and endogenous thrombopoietin levels are inappropriately low or normal…

Diagnosis — A Diagnosis of Exclusion

There is no single confirmatory test for ITP. The diagnosis rests on isolated thrombocytopenia with a normal remainder of the CBC and a blood smear that confirms true thrombocytopenia and excludes other diagnoses. **Essential evaluation:** - **CBC and reticulocyte count:** thrombocytopenia should be isolated. Anemia (unless from bleeding) or leukocyte abnormalities point to another diagnosis. - **Peripheral blood smear:** the single most important test. Confirms low platelets, often with large/young platelets; excludes pseudothrombocytopenia (EDTA-induced platelet clumping — repeat with a…

First-Line Treatment

The decision to treat is based on bleeding and bleeding risk, not the platelet number in isolation. Asymptomatic adults with platelets ≥30 × 10⁹/L can often be observed. Treatment is indicated for clinically significant bleeding, or for very low counts (generally <20–30 × 10⁹/L), or before procedures. **Corticosteroids (first-line for most patients):** - **Prednisone/prednisolone** 1 mg/kg/day (typical range 0.5–2 mg/kg/day) for up to 2–3 weeks, then tapered. Response usually within 1 week. - **High-dose dexamethasone** 40 mg daily for 4 days, repeated every 2–4 weeks for up to 3–4 cycles,…

Second-Line Therapy — TPO-RAs, Rituximab, Fostamatinib, and Splenectomy

Roughly two-thirds of adults require second-line therapy for persistent or chronic ITP. Modern guidelines favor medical therapy (particularly TPO-RAs) before splenectomy, and recommend delaying splenectomy for at least 12 months from diagnosis when possible, because some patients remit. **Thrombopoietin receptor agonists (TPO-RAs):** These agents stimulate megakaryocyte proliferation and platelet production — directly addressing the impaired-production arm of ITP. Response rates are high (~60–90%). - **Eltrombopag** — oral once daily; requires separation from polyvalent cations (calcium,…

Special Situations and Emergencies

**Life-threatening bleeding (e.g. intracranial or major GI hemorrhage):** Treat aggressively and in combination — IV corticosteroids (e.g. high-dose methylprednisolone), IVIG 1 g/kg, and continuous or repeated platelet transfusions. Consider adjuncts such as antifibrinolytics (tranexamic acid) for mucosal bleeding, and urgent surgical/interventional control of the bleeding source. Emergency splenectomy or emergent rituximab may be considered in refractory catastrophic bleeding. **Pregnancy:** ITP is a common cause of thrombocytopenia in pregnancy and must be distinguished from gestational…