What is the best workup for thrombocytopenia?

Diagnostic Workup for Thrombocytopenia

The best workup for thrombocytopenia should begin with a complete blood count with platelet confirmation, peripheral blood smear examination, and basic coagulation tests, followed by targeted second-line testing based on clinical presentation. 1

Initial Evaluation

First-line Tests (Essential for All Patients)

• Complete blood count (CBC) with platelet count confirmation
• Peripheral blood smear examination by qualified hematologist/pathologist
• Basic coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time
• Patient history (focusing on medications, systemic symptoms, bleeding history)
• Physical examination (looking for petechiae, purpura, lymphadenopathy, hepatosplenomegaly)

Important Clinical Considerations

• Confirm true thrombocytopenia by collecting blood in a tube containing heparin or sodium citrate to exclude pseudothrombocytopenia 2
• Determine if thrombocytopenia is acute or chronic by reviewing previous platelet counts
• Assess severity: patients with counts <10 × 10³/μL have high risk of serious bleeding 2
• Evaluate for systemic illness that might indicate secondary causes

Second-line Tests (Based on Initial Findings)

For Suspected Immune Thrombocytopenia (ITP)

• Quantitative immunoglobulin level measurement (especially in children) 3
• HIV testing (recommended for all adult patients) 3, 1
• Hepatitis C virus testing (recommended for all adult patients) 3, 1
• Helicobacter pylori testing (preferably with urea breath test or stool antigen) 3, 1
• Blood group (Rh) typing (if anti-D immunoglobulin therapy is being considered) 3, 1

For Suspected Inherited Platelet Disorders

• Platelet function testing (light transmission aggregometry) 3, 1
• Assessment of platelet granule release 3, 1
• Flow cytometry for platelet surface glycoproteins 3, 1
• Genetic/genomic testing when inherited thrombocytopenia is suspected 1

For Suspected Secondary Causes

• Antinuclear antibodies (for autoimmune diseases) 3, 1
• Antithyroid antibodies and thyroid function tests 3
• Antiphospholipid antibodies (including anticardiolipin and lupus anticoagulant) 3, 1
• Direct antiglobulin test (if immune-mediated hemolysis is suspected) 3, 1
• Von Willebrand factor (VWF) screening tests (VWF antigen, ristocetin cofactor activity, FVIII) 3, 1

Bone Marrow Examination

Bone marrow examination is not routinely needed but is indicated in specific circumstances:

• Patients older than 60 years 1
• Patients with systemic symptoms or abnormal signs 1
• Persistent thrombocytopenia (>6-12 months) 1
• Patients unresponsive to initial therapy 1
• Patients before initiation of treatment with corticosteroids or before splenectomy (suggested, not strongly recommended) 3

The American Society of Hematology specifically states that bone marrow examination is not necessary in:

• Children and adolescents with typical features of ITP (grade 1B recommendation) 3
• Children who fail IVIg therapy (grade 1B recommendation) 3

Common Pitfalls to Avoid

1. Overdiagnosis: Performing unnecessary tests when clinical presentation is typical of ITP 1
2. Missing secondary causes: Failing to test for HIV or HCV in adults 1
3. Pseudothrombocytopenia: Not excluding EDTA-dependent platelet agglutination 1
4. Overlooking inherited thrombocytopenias: Not carefully examining peripheral smear for giant or small platelets 1
5. Unnecessary bone marrow examination: In children with typical ITP features 3

Follow-up Testing

For patients diagnosed with ITP and started on treatment:

• Obtain complete blood counts weekly during dose adjustment phase 4
• Monitor monthly following establishment of stable treatment 4
• Continue weekly monitoring for at least 2 weeks following discontinuation of treatment 4

This systematic approach to thrombocytopenia workup allows for efficient diagnosis while avoiding unnecessary testing, leading to appropriate management based on the underlying cause.