What is the work-up for thrombocytopenia (low platelet count)?

Work-up for Thrombocytopenia (Low Platelet Count)

The initial workup for thrombocytopenia should include 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 Testing

• Complete blood count (CBC) with platelet count confirmation
• Peripheral blood smear examination by a qualified hematologist/pathologist
• Basic coagulation tests:
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (APTT)
  • Thrombin time

Essential Additional Testing

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

Specialized Testing Based on Clinical Presentation

Platelet Function Assessment

• Light transmission aggregometry
• Assessment of platelet granule release
• Flow cytometry for platelet surface glycoproteins

Additional Testing for Specific Scenarios

• Von Willebrand factor (VWF) screening tests:
  • VWF antigen
  • Ristocetin cofactor activity
  • Factor VIII coagulant activity
• Coagulation factor assays (FII, FV, FVII, FX, FXIII)
• Thyroid function tests
• Iron studies
• Antinuclear antibody (ANA) testing (when autoimmune disease is suspected)
• Direct antiglobulin test (DAT) (when immune-mediated hemolysis is suspected)
• Antiphospholipid antibodies (when thrombosis is present with thrombocytopenia)
• Genetic/genomic testing (when inherited thrombocytopenia is suspected)

Bone Marrow Examination

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

• Patients older than 60 years
• Patients with systemic symptoms or abnormal signs
• Persistent thrombocytopenia
• Patients unresponsive to initial therapy
• Before initiation of treatment with corticosteroids or splenectomy 2, 1

The American Society of Hematology specifically recommends against bone marrow examination in:

• Children and adolescents with typical features of ITP
• Children who fail IVIg therapy 1

Monitoring and Management

• For patients diagnosed with ITP and started on treatment:
  • Obtain complete blood counts weekly during the dose adjustment phase
  • Monitor monthly following establishment of stable treatment
  • Continue weekly monitoring for at least 2 weeks following discontinuation of treatment 1, 3

Common Pitfalls to Avoid

1. Overdiagnosis: Performing unnecessary tests when the clinical picture is clear
2. Missing secondary causes: Failing to test for HIV or HCV
3. Pseudo-thrombocytopenia: Not excluding EDTA-dependent platelet agglutination
4. Overlooking inherited thrombocytopenias: Not carefully examining the peripheral smear for giant or small platelets 1
5. Unnecessary bone marrow examination: The American Society of Hematology guideline states that further diagnostic studies are generally not indicated in the routine work-up of patients with suspected ITP, assuming that the history, physical examination, and blood counts are compatible with the diagnosis 2

Special Considerations

Pregnancy

• Measure blood pressure to rule out preeclampsia
• Perform liver function testing
• Test for HIV antibody in patients with risk factors 2

Thrombocytopenia with Thrombosis

Be alert for conditions where both thrombosis and thrombocytopenia can occur:

• Antiphospholipid syndrome
• Heparin-induced thrombocytopenia
• Thrombotic microangiopathies
• Vaccine-induced immune thrombotic thrombocytopenia 4, 5

By following this systematic approach to the work-up of thrombocytopenia, clinicians can efficiently identify the underlying cause and initiate appropriate management to reduce morbidity and mortality associated with this condition.