What investigations should be done for a patient presenting with thrombocytopenia?

Investigations for Thrombocytopenia

The diagnostic approach for thrombocytopenia should include a comprehensive history, physical examination, complete blood count with peripheral blood smear examination, and targeted laboratory testing based on clinical suspicion. 1

Initial Diagnostic Workup

History and Physical Examination

• Evaluate for conditions associated with autoimmune thrombocytopenia: HIV, HCV, other infections, autoimmune disorders (SLE), malignancies (lymphoproliferative disorders), and recent vaccinations 1
• Assess for liver disease including alcoholic cirrhosis 1
• Review medication history (prescription and non-prescription drugs), alcohol use, quinine consumption, and environmental toxin exposure 1
• Evaluate for bone marrow diseases: myelodysplastic syndromes, leukemias, other malignancies, fibrosis, aplastic anemia, and megaloblastic anemia 1
• Check for recent transfusions (possible post-transfusion purpura) and recent immunizations 1
• Consider inherited thrombocytopenia syndromes 1
• Physical examination should be normal except for bleeding manifestations in ITP; presence of splenomegaly, hepatomegaly, lymphadenopathy, or constitutional symptoms suggests alternative diagnoses 1

Laboratory Tests

• Complete blood count with differential 1, 2
• Peripheral blood smear examination by a qualified hematologist/pathologist to:
  • Confirm true thrombocytopenia (exclude pseudothrombocytopenia due to EDTA-dependent platelet agglutination) 1
  • Evaluate platelet morphology (giant or small platelets may indicate inherited thrombocytopenia) 1
  • Look for abnormalities inconsistent with ITP (schistocytes, leukocyte inclusion bodies) 1
• Reticulocyte count if anemia is present 1

Additional Testing Based on Clinical Suspicion

Recommended for Most Patients

• HIV and HCV testing regardless of risk factors 1
• H. pylori testing in adults (preferably with urea breath test or stool antigen test) 1
• Blood group Rh(D) typing if anti-D immunoglobulin therapy is being considered 1

Bone Marrow Examination

• Indicated in patients:
  • Older than 60 years 1
  • With systemic symptoms or abnormal signs 1
  • When splenectomy is considered 1
  • With abnormalities in other cell lines 3, 4
• Should include both aspirate and biopsy 1
• Flow cytometry and cytogenetic testing should be considered to identify secondary causes like CLL or myelodysplastic syndromes 1, 3

Tests of Potential Utility

• Antiplatelet antibody assays (not routinely recommended as PaIgG is elevated in both immune and non-immune thrombocytopenia) 1
• Antiphospholipid antibodies if symptoms of antiphospholipid syndrome are present 1
• Antinuclear antibodies (may predict chronicity in childhood ITP) 1
• Antithyroid antibody and thyroid function testing (8-14% of ITP patients develop clinical hyperthyroidism) 1

Special Considerations

For Suspected Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)

• D-dimer measurement 1
• Coagulation screen including Clauss fibrinogen assay 1
• Anti-PF4 antibodies ELISA assay 1
• Appropriate imaging based on symptoms to identify thrombosis 1

For Suspected Myelodysplastic Syndrome with Isolated Thrombocytopenia

• Evaluate for dysplastic changes in peripheral blood 3, 4
• Consider vitamin B12 and folate levels 3
• Bone marrow examination with cytogenetics is crucial to distinguish from ITP 3, 4

Diagnostic Pitfalls to Avoid

• Failing to exclude pseudothrombocytopenia (EDTA-dependent platelet clumping) 1
• Overlooking drug-induced thrombocytopenia 2
• Misdiagnosing myelodysplastic syndrome with isolated thrombocytopenia as ITP 4
• Not considering pregnancy-related causes (preeclampsia, HELLP syndrome) in pregnant women 2
• Missing life-threatening causes requiring urgent treatment (TTP, DIC, acute promyelocytic leukemia) 5

Diagnostic Algorithm

1. Assess severity of thrombocytopenia and presence of bleeding
2. Review peripheral blood smear to confirm thrombocytopenia and evaluate for other abnormalities
3. Determine if thrombocytopenia is isolated or associated with other cytopenias
4. Perform targeted testing based on clinical presentation and initial findings
5. Consider bone marrow examination in appropriate patients
6. Evaluate response to ITP-specific therapy if diagnosis remains uncertain 1