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: platelets of 50K or more are generally adequate for vaginal or cesarean delivery, and neuraxial anesthesia is considered low risk at 70K or more if the count is stable and there is no other coagulopathy (ACOG Practice Bulletin 207, 2019; SOAP consensus 2021).
• 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 No. 207: Thrombocytopenia in Pregnancy (Obstet Gynecol 2019;133:e181-e193)
• Cines & Bussel — How I treat idiopathic thrombocytopenic purpura (Cines & Bussel, Blood 2005)
• SOAP 2021 — The Society for Obstetric Anesthesia and Perinatology interdisciplinary consensus statement on neuraxial procedures in obstetric patients with thrombocytopenia (Bauer et al., Anesth Analg 2021;132:1531-1544)