What is the most accurate statement regarding the cause and management of idiopathic thrombocytopenic purpura (ITP)?

Idiopathic Thrombocytopenic Purpura (ITP): Pathophysiology and Management

Idiopathic thrombocytopenic purpura is caused by antiplatelet immunoglobulin G, but these antibodies originate primarily in the bone marrow and lymphoid tissues rather than the spleen, and splenomegaly is typically absent in most cases. 1

Pathophysiology of ITP

ITP is an acquired immune-mediated disorder characterized by:

• Autoantibody production: Primarily IgG autoantibodies directed against platelet membrane glycoproteins
• Normal bone marrow: With adequate or increased megakaryocytes
• Isolated thrombocytopenia: Defined as platelet count <100 × 10^9/L 1

Key Characteristics

1. Origin of antiplatelet antibodies:

   • Antibodies are produced by B lymphocytes in the bone marrow, lymph nodes, and other lymphoid tissues
   • The spleen is involved in platelet destruction but is not the primary source of antibody production 1

2. Absence of splenomegaly:

   • Splenomegaly is typically absent in ITP
   • Data from case series indicate the spleen may be palpable in only about 12% of children with ITP 1
   • The absence of splenomegaly is an important diagnostic feature that helps distinguish ITP from other causes of thrombocytopenia

3. Normal coagulation studies:

   • Prothrombin time (PT) is normal in ITP
   • Only the platelet count is affected; other coagulation parameters remain normal 1

4. Gender distribution:

   • Recent epidemiologic data suggest the incidence is approximately equal for both sexes
   • Exception: In mid-adult years (30-60 years), ITP is more prevalent in women 1

Diagnostic Approach

The diagnosis of ITP is based on:

• Complete blood count showing isolated thrombocytopenia
• Normal peripheral blood smear (except for reduced platelets)
• Absence of other causes of thrombocytopenia 1

Peripheral Blood Smear Findings Consistent with ITP:

• Thrombocytopenia
• Platelets normal in size or slightly larger than normal
• Normal red blood cell morphology
• Normal white blood cell morphology 1

Management of ITP in Children vs. Adults

Pediatric ITP Management:

• Natural history: Usually self-limited with at least two-thirds recovering spontaneously within 6 months 1
• Observation: Children with no bleeding or mild bleeding (skin manifestations only) should be managed with observation alone regardless of platelet count 1
• Pharmacologic treatment: For children requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids is recommended as first-line 1
• Splenectomy: Not required for most pediatric cases
  • Splenectomy is considered only after 6-12 months of chronic disease
  • Success rate is approximately 75% when performed
  • Contraindicated temporarily before age 5 and permanently in immune deficiency 2

Adult ITP Management:

• Natural history: Typically follows a chronic course with insidious onset 1
• First-line therapy: Corticosteroids (prednisone) 3
• Second-line therapy: Splenectomy offers approximately 70% chance of cure for adults with chronic ITP 4
• Refractory cases: Various options including immunosuppressive agents, TPO receptor agonists, and rituximab 1

Common Pitfalls and Caveats

1. Misdiagnosis: Failure to exclude secondary causes of thrombocytopenia

   • Always consider HIV, HCV, medications, and autoimmune disorders 1

2. Overtreatment: Treating asymptomatic patients with mild thrombocytopenia

   • Children with no bleeding or mild bleeding should be managed with observation alone 1

3. Mortality risk factors: Though generally considered benign, fatal cases can occur in:

   • Older patients
   • Chronic, refractory patients with history of hemorrhage
   • Patients with concomitant bleeding diatheses 5

4. Bone marrow examination: Generally unnecessary in children and adolescents with typical features of ITP 1

In conclusion, when evaluating the statements about ITP, option (a) is partially correct but misleading as antibodies originate primarily in bone marrow and lymphoid tissues rather than the spleen; option (b) is incorrect as splenomegaly is typically absent; option (c) is incorrect as prothrombin time is normal; option (d) is incorrect as splenectomy is not required for most pediatric cases; and option (e) is incorrect regarding the gender ratio.