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BASICS

  • ITP: immune-mediated platelet destruction and impaired thrombopoiesis
  • Defined as platelet count <100 × 10⁹/L after excluding other causes
  • Classified as newly diagnosed (<3 months), persistent (3–12 months), chronic (>12 months)
  • Primary (isolated) vs secondary (associated with other disorders)
  • Pediatric ITP typically acute, post-viral, with spontaneous resolution in >80%
  • Adult ITP often chronic with rare spontaneous remission

EPIDEMIOLOGY

  • Pediatric peak age: 2 to 4 years
  • Chronic ITP peak: >50 years (higher incidence >60 years)
  • Gender: Pediatric M=F; Chronic adult female > male (1.2–1.7:1)
  • Incidence: Pediatric 1.9–6.4/100,000/year; Adult 1.6/100,000/year
  • Seasonal peak: spring and early summer (supports viral trigger theory)
  • Prevalence: ~11.2/100,000 in one population

ETIOLOGY AND PATHOPHYSIOLOGY

  • IgG autoantibodies target platelet glycoproteins IIb/IIIa, Ib/IX, Ia/IIa, VI
  • CD8+ T cell-mediated platelet destruction
  • Autoantibodies impair megakaryocyte maturation → decreased platelet production
  • Fc-independent desialylation pathways implicated in treatment refractoriness
  • Associated with immune checkpoint inhibitor therapy

RISK FACTORS

  • Autoimmune thrombocytopenia (e.g., Evans syndrome)
  • Immunodeficiencies (e.g., CVID)
  • Drug reactions (quinidine, vancomycin, penicillin, sulfonamides)
  • Infections: H. pylori, hepatitis C, HIV, CMV, varicella, measles, rubella, influenza, EBV, Whipple disease
  • Vaccinations (MMR vaccine risk lower than natural viral infection)
  • Bone marrow transplantation
  • Connective tissue diseases: SLE, antiphospholipid syndrome
  • Lymphoproliferative disorders

DIAGNOSIS

History

  • Often asymptomatic, incidental low platelet count
  • Bleeding risk increases as platelet count decreases (<40 × 10⁹/L traumatic bleeding; <30 × 10⁹/L bruising, epistaxis, menorrhagia)
  • Spontaneous bleeding risk <20 × 10⁹/L, rare intracranial hemorrhage with trauma
  • Female gender, NSAID exposure increase bleeding risk

Physical Exam

  • Petechiae, ecchymoses, epistaxis, gingival bleeding
  • Hemorrhagic bullae in severe cases
  • No hepatosplenomegaly or lymphadenopathy

Differential Diagnosis

  • Acute leukemia
  • TTP, HUS, DIC
  • Platelet clumping artifacts
  • Sepsis-related thrombocytopenia
  • Myelodysplastic syndromes
  • Marrow suppression (malignancy, drugs, viruses, megaloblastic anemia)
  • Posttransfusion
  • Gestational thrombocytopenia
  • Neonatal isoimmune purpura
  • Congenital thrombocytopenias
  • Alcohol-induced thrombocytopenic purpura

Diagnostic Tests

  • CBC and peripheral smear: isolated thrombocytopenia, giant platelets
  • Normal RBC and WBC morphology
  • Normal PT/PTT
  • Hepatitis B, C, HIV serologies in adults
  • Immunoglobulin levels in pediatric cases for CVID
  • Additional tests only if atypical features (fever, weight loss, lymphadenopathy, pancytopenia)
  • Bone marrow biopsy not routinely needed unless atypical features present
  • Platelet antibody testing and reticulated platelet analysis may assist in equivocal cases

TREATMENT

General Measures

  • Treatment based on platelet count and bleeding risk
  • Treat if platelet <30 × 10⁹/L
  • Goal: adequate hemostasis, not necessarily normal count
  • Outpatient if stable and no significant bleeding risk
  • Admit if active bleeding

Medication

Pediatric

  • Observation if mild/no bleeding regardless of platelet count
  • IVIG single dose 0.8–1.0 g/kg if rapid platelet increase needed (avoid in IgA deficiency)
  • Short-course corticosteroids (e.g., prednisone 2 mg/kg/day for 2 weeks, taper over 3 weeks)
  • Anti-Rho(D) immunoglobulin in Rh+ nonsplenectomized children (avoid if hemolysis)
  • Second-line: splenectomy, rituximab, high-dose dexamethasone, other immunosuppressants
  • Thrombopoietin receptor agonists show promise in chronic pediatric ITP

Adult

  • First line: corticosteroids—dexamethasone 40 mg/day × 4 days preferred
  • If steroids contraindicated: IVIG (1–2 g/kg once) or anti-D (50–75 µg/kg once) in Rh+ nonsplenectomized adults
  • Second line: splenectomy if refractory
  • Alternatives: thrombopoietin receptor agonists (eltrombopag, romiplostim), rituximab, immunosuppressants
  • FDA-approved agents: avatrombopag, fostamatinib

ITP in Pregnancy

  • Distinguish from gestational thrombocytopenia, preeclampsia
  • Steroids and IVIG safe and first line
  • Delivery mode based on obstetric indications, platelet autoantibodies cross placenta causing neonatal thrombocytopenia
  • Consider prednisone/IVIG 2–3 weeks prior to delivery

ITP Secondary to HIV or HCV

  • Treat underlying infection first
  • If needed, corticosteroids, IVIG, anti-D; splenectomy second line

Emergency Treatment

  • For severe bleeding (intracranial, GI, massive hematuria): IV methylprednisolone 1 g/day × 3 days, IVIG, platelet transfusion
  • Recombinant factor VIIa, antifibrinolytics may be adjuncts
  • Emergent splenectomy reported

ISSUES FOR REFERRAL

  • Hematology consult for acute bleeding or refractory disease

SURGERY/OTHER PROCEDURES

  • Splenectomy has low mortality (<1%)
  • Laparoscopic approach preferred in suitable patients
  • Pre-op vaccines: pneumococcal, meningococcal, Hib
  • Consider lifelong prophylactic antibiotics
  • Raise platelet count ≥20 × 10⁹/L prior to surgery

ONGOING CARE

  • Monitor platelet counts weekly on steroids, monthly if stable
  • Repeat short course dexamethasone if platelet count response inadequate

PATIENT EDUCATION

  • Avoid trauma, contact sports
  • Avoid anticoagulants, antiplatelet agents, NSAIDs

PROGNOSIS

  • Pediatric acute ITP: 80–85% spontaneous recovery within 2 months
  • 15% progress to chronic ITP
  • Chronic ITP: 10–20% spontaneous remission; ~10% refractory
  • Morbidity mainly from bleeding; 1% mortality from intracranial hemorrhage

COMPLICATIONS

  • Bleeding-related morbidity and mortality
  • Treatment-related adverse effects

REFERENCES

  1. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866.

Clinical Pearls

  • ITP diagnosis is by exclusion with platelet count <100 × 10⁹/L
  • Pediatric ITP often self-resolves; adult disease is often chronic
  • Treatment aims for hemostasis, not normal platelet count
  • Splenectomy is effective second-line treatment after failed medical therapy
  • Monitor carefully for bleeding risks and adverse treatment effects