What is the workup and treatment for thrombocytopenia (low platelet count)?

Workup and Treatment for Thrombocytopenia

The diagnosis of thrombocytopenia requires confirmation of a true low platelet count through history, physical examination, complete blood count, and peripheral blood smear examination, followed by targeted testing to determine the underlying cause. 1, 2

Diagnostic Approach

Initial Evaluation

• Confirm true thrombocytopenia by ruling out pseudothrombocytopenia (platelet clumping due to EDTA) by examining peripheral blood smear or collecting blood in tubes containing heparin or sodium citrate 2, 3
• Review complete blood count and peripheral blood smear to exclude other causes of thrombocytopenia 1, 2
• Determine if thrombocytopenia is isolated or associated with other cytopenias 2, 4
• Assess for bleeding symptoms - patients with platelet counts >50 × 10³/μL are generally asymptomatic, while those with counts <10 × 10³/μL have high risk of serious bleeding 3, 5

Additional Testing Based on Clinical Suspicion

• HIV testing for patients with risk factors 1, 2
• Hepatitis B and C virus testing 1, 2
• Helicobacter pylori testing 1, 2
• Direct antiglobulin test to rule out Evans syndrome 1
• Abdominal imaging (CT/ultrasound) if splenomegaly is suspected 1, 2
• Bone marrow examination for persistent thrombocytopenia (>6-12 months) or non-response to therapy 1, 2

Treatment Approach

When to Treat

• Treatment is not required for patients with no bleeding or mild skin manifestations (petechiae, purpura), regardless of platelet count 2, 6
• Treatment is indicated for patients with platelet counts <10,000/μL or active bleeding 1, 5
• Patients with platelet counts between 10,000-30,000/μL with significant mucous membrane bleeding should receive treatment 1

First-Line Treatment Options for Primary ITP

• Corticosteroids: Prednisone 0.5-2 mg/kg/day until platelet count increases (typically 30-50 × 10⁹/L), followed by rapid taper 6
• High-dose dexamethasone (40 mg/day for 4 days) is an alternative with high initial response rates 6
• Intravenous immunoglobulin (IVIg) at 0.8-1 g/kg for rapid platelet count elevation in emergency situations 1, 6
• Anti-D immunoglobulin for Rh-positive, non-splenectomized patients 1, 6

Second-Line Treatment Options

• Thrombopoietin receptor agonists (TPO-RAs) such as romiplostim (initial dose 1 mcg/kg subcutaneously weekly, adjusted to maintain platelet count ≥50 × 10⁹/L) 7
• Rituximab (commonly used off-label) 6, 8
• Splenectomy (traditionally considered principal option for long-term ITP management) 1, 6

Emergency Management

• For life-threatening bleeding, use combination therapy: high-dose parenteral glucocorticoids, IVIg, and platelet transfusions 1, 6
• Hospitalization is appropriate for patients with platelet counts <20,000/μL who have significant mucous membrane bleeding 1

Special Populations

• Pregnant women with ITP and platelet counts >50,000/μL do not routinely require treatment 1
• Treatment is required for pregnant women with platelet counts <10,000/μL, or 10,000-30,000/μL with bleeding in second/third trimester 1
• IVIg is appropriate initial treatment for pregnant women with platelet counts <10,000/μL in the third trimester 1

Treatment of Secondary Thrombocytopenia

• For HCV-associated thrombocytopenia, antiviral therapy should be considered if not contraindicated 6
• For HIV-associated thrombocytopenia, antiretroviral therapy can improve cytopenias 6
• For immune checkpoint inhibitor-related thrombocytopenia, management depends on severity 1:
  • Grade 1: Continue immune checkpoint inhibitor with close monitoring
  • Grade 2-4: Hold immune checkpoint inhibitor and treat with corticosteroids; consult hematology for grade 3-4

Common Pitfalls and Considerations

• Long-term corticosteroid use should be avoided due to significant adverse effects 6
• Discontinue romiplostim if platelet count does not increase to avoid clinically important bleeding after 4 weeks at maximum dose (10 mcg/kg) 7
• Monitor for thrombotic complications with TPO-RAs, especially in patients with risk factors 7
• Patients with platelet counts <50 × 10³/μL should avoid activities with high risk of trauma 3