Immune Thrombocytopenia (ITP)

Definition

ITP is an acquired autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 10⁹/L) in the absence of other identifiable causes. The diagnosis remains one of exclusion - no single laboratory test confirms it with certainty.

Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 968

Classification

Type	Timing/Description
Newly diagnosed	Within 3 months of diagnosis
Persistent	3-12 months; no spontaneous remission
Chronic	Lasting >12 months
Severe	Bleeding symptoms mandating treatment
Primary	Idiopathic (no identifiable cause)
Secondary	Associated with SLE, APS, HIV, HCV, H. pylori, lymphoproliferative disorders, or drugs

Pathophysiology

Two main mechanisms drive thrombocytopenia:

Accelerated platelet destruction: IgG autoantibodies bind platelet surface glycoproteins (GPIIb/IIIa, GPIb/IX), triggering reticuloendothelial clearance - primarily in the spleen
Impaired platelet production: Antibodies also suppress megakaryopoiesis, which is why thrombopoietin receptor agonists work

Antiplatelet antibodies are only detectable in ~60% of patients. In children, ~60% have a preceding infection - suggesting molecular mimicry where immune responses against an organism cross-react with platelet antigens (especially HIV, HCV, H. pylori).

The Washington Manual of Medical Therapeutics, p. 757
Henry's Clinical Diagnosis, p. 968

Clinical Presentation

Typically mild mucocutaneous bleeding, petechiae, purpura, or incidental thrombocytopenia on routine CBC
Occasionally major bleeding (intracranial hemorrhage is rare but life-threatening)
Bleeding risk is highest when platelets <30 × 10⁹/L
Splenomegaly is NOT typically present (its presence should prompt alternative diagnoses)

Diagnosis

Diagnosis of exclusion - no confirmatory test.

Essential workup:

History and physical examination
CBC + peripheral blood smear (confirm count, rule out clumping, assess morphology)
HIV, HCV serology
H. pylori testing
Blood group (Rh type)
Direct antiglobulin test (DAT/Coombs)
Quantitative immunoglobulins

Not routinely needed:

Antiplatelet antibody titers (poor sensitivity, low NPV - not diagnostic)
Bone marrow biopsy (reserved for atypical cases, age >60, or treatment failure)

Treatment

Indications for Treatment

Treatment is based on bleeding risk and platelet count, not the count alone. The therapeutic goal is a safe platelet count (typically ≥30 × 10⁹/L) to prevent major bleeding, not necessarily normalization.

First-Line Therapy

Agent	Dose/Regimen	Notes
Dexamethasone	40 mg orally × 4 days (can repeat)	Preferred over prednisone by many centers
Prednisone	1 mg/kg/day with prolonged taper	Classic glucocorticoid regimen
IVIG	1 g/kg × 1-2 doses	Used to hasten response; works within 24-48 hours
Anti-D immunoglobulin (WinRho)	For Rh-positive, non-splenectomized patients	Black box warning for severe hemolysis; rarely used now

Most patients respond within 1-3 weeks, but 30-40% relapse.

Second-Line Therapy (Refractory/Relapsed ITP)

Agent	Mechanism	Key Data
Splenectomy	Removes main site of platelet destruction	~2/3 achieve durable complete response
Rituximab (anti-CD20)	Depletes B cells	~25% sustained remission at 12 months
TPO receptor agonists	Stimulate platelet production	>90% platelet response; response in 5-7 days
Fostamatinib	Syk kinase inhibitor; reduces macrophage phagocytosis	18% stable response; for heavily pre-treated patients

Three approved TPO-RAs:

Romiplostim - subcutaneous, weekly
Eltrombopag - oral, once daily
Avatrombopag - oral, once daily (a 2026 systematic review [PMID 41863412] confirmed real-world safety and efficacy)

Note: TPO-RA carry a risk of thromboembolic events.

Before splenectomy, vaccinate against: pneumococcus, meningococcus, and Haemophilus influenzae type B.

Other/Salvage Options

Danazol (androgen therapy)
Mycophenolate mofetil, azathioprine, cyclosporine
Combined IVIG + steroids
Platelet transfusion (reserved for life-threatening bleeds; short-lived benefit due to rapid destruction)

Secondary ITP Management

Treat the underlying cause (e.g., antiretrovirals for HIV-ITP, H. pylori eradication, discontinue offending drug)
Drug-induced ITP: withdrawal of the causative drug is the primary intervention
Additionally use therapies similar to primary ITP as needed

Recent Evidence (2025-2026)

A 2025 meta-analysis (PMID 41382219) confirmed dapsone as an effective second-line option in adult ITP
A 2026 systematic review (PMID 41863412) confirmed real-world safety and efficacy of avatrombopag in adults with ITP

Sources: Washington Manual of Medical Therapeutics; Henry's Clinical Diagnosis and Management by Laboratory Methods; Rodeghiero et al., Blood 2009; Provan et al., Blood 2010

This is a shared conversation. Sign in to Orris to start your own chat.