Immune Thrombocytopenic Purpura (ITP)

Risk factors

• Children: recent viral illness (URI, varicella, MMR vaccine)
• Adults: associated with autoimmune disease (SLE, antiphospholipid syndrome), lymphoproliferative disorders (CLL), chronic infection (HIV, HCV, H. pylori), drugs
• Drug-induced: heparin (HIT distinct), quinine, sulfonamides, vancomycin, linezolid, abciximab/eptifibatide, valproate
• Common variable immunodeficiency
• Pregnancy (gestational thrombocytopenia far more common, ITP rarer)

Pathophysiology

IgG autoantibodies target platelet glycoproteins (GPIIb/IIIa, GPIb/IX). Antibody-coated platelets are cleared by reticuloendothelial macrophages, primarily in the spleen. T-cell dysregulation, impaired megakaryopoiesis (suppressed by autoantibodies and reduced thrombopoietin response), and direct cytotoxic platelet destruction also contribute.

Clinical presentation

Differential diagnosis

• Heparin-induced thrombocytopenia (HIT) — Heparin exposure 5-14 days prior, thrombosis (not bleeding), 4T score, anti-PF4 antibody; STOP heparin, use non-heparin anticoagulant
• TTP — Pentad (often partial): microangiopathic hemolytic anemia, thrombocytopenia, neurologic, renal, fever; schistocytes; LOW ADAMTS13
• DIC — Thrombocytopenia + prolonged PT/PTT + low fibrinogen + elevated D-dimer + clinical bleeding/thrombosis in critically ill
• Drug-induced thrombocytopenia — Temporal relationship to drug; recovery in 5-7 days after discontinuation
• Pseudothrombocytopenia — EDTA-dependent platelet clumping in vitro; repeat in citrate tube — normal platelet count
• Gestational thrombocytopenia — Mild (>70K), late third trimester, no prior history, resolves postpartum; cannot reliably distinguish from ITP in early pregnancy
• Bone marrow failure (aplastic anemia, MDS, leukemia) — Other cytopenias, abnormal cells on smear, abnormal marrow
• Hypersplenism — Splenomegaly, often other cytopenias, underlying cirrhosis
• Secondary ITP — Lupus, HIV, HCV, H. pylori, CLL — screen all newly diagnosed ITP

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Isolated thrombocytopenia<br/>Plt <100K] --> B[Review smear]
  B --> C{Schistocytes?}
  C -->|Yes| D[TTP / HUS / DIC<br/>NOT ITP]
  C -->|No| E{Clumping?}
  E -->|Yes| F[Pseudothrombocytopenia<br/>repeat in citrate]
  E -->|No| G[Check HIV, HCV, HBV,<br/>H. pylori, ANA<br/>drug history]
  G --> H{Secondary cause?}
  H -->|Yes| I[Treat underlying cause]
  H -->|No| J[Primary ITP]
  J --> K{Plt count}
  K -->|>30K, no bleeding| L[Observe]
  K -->|<30K or bleeding| M[Steroids ± IVIG]
  M --> N{Response?}
  N -->|No / Relapse| O[TPO-RA, rituximab,<br/>splenectomy, fostamatinib]

Treatment

Complications

• Major bleeding: intracranial hemorrhage (~1% adults, lower in children), severe GI or genitourinary hemorrhage
• Quality of life: fatigue, treatment burden, mood/anxiety
• Treatment-related: steroid toxicity, post-splenectomy sepsis, TPO-RA-associated thrombosis and hepatotoxicity, rituximab-induced hypogammaglobulinemia and HBV reactivation
• Chronic ITP develops in ~20% of children and the majority of adults
• Pregnancy: increased neonatal thrombocytopenia risk (passive antibody transfer); monitor newborn

PANCE pearls

• ITP is a diagnosis of EXCLUSION — isolated thrombocytopenia with otherwise normal CBC, smear, and coagulation studies, no splenomegaly, no other systemic findings.
• Pediatric ITP usually self-limits within 6 months — observation alone is appropriate for many cases without significant bleeding.
• ASH 2019 guidelines support observation for adults with platelets >30K without bleeding — reduces unnecessary steroid exposure.
• Dexamethasone 40 mg/day × 4 days is increasingly preferred over prolonged prednisone for first-line — faster response, less cumulative toxicity.
• Pregnancy and ITP: ACOG recommends platelet goal >50K for vaginal delivery, >80K for neuraxial anesthesia/C-section.
• Always screen new ITP for HIV, HCV, and H. pylori — treatable causes of secondary ITP.
• If patient has thrombocytopenia + microangiopathic hemolysis, do NOT diagnose ITP — think TTP, HUS, DIC, HELLP.
• TPO-RA chronic therapy can cause thrombosis — monitor and counsel.

References

• ASH 2019 — American Society of Hematology 2019 guidelines for immune thrombocytopenia (Neunert et al., Blood Adv 2019)
• International Consensus 2019 — Updated international consensus report on the investigation and management of primary immune thrombocytopenia (Provan et al., Blood Adv 2019)
• ACOG 2019 — ACOG Practice Bulletin: Thrombocytopenia in Pregnancy (ACOG)
• Cines & Bussel — How I treat idiopathic thrombocytopenic purpura (Cines & Bussel, Blood 2005)