What laboratory tests should be ordered to investigate thrombocytopenia (low platelet count)?

Laboratory Tests for Investigating Thrombocytopenia

The initial laboratory evaluation of thrombocytopenia should include a complete blood count with peripheral blood smear examination, coagulation studies, and targeted testing based on clinical presentation to determine the underlying cause. 1

First-Line Laboratory Tests

• Complete blood count (CBC) to confirm thrombocytopenia and evaluate other cell lines for concurrent abnormalities 1, 2
• Peripheral blood smear examination to assess platelet morphology, size variations, and exclude pseudothrombocytopenia due to EDTA-dependent platelet agglutination 1
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) to evaluate for coagulation disorders 2
• Reticulocyte count to assess for bone marrow response and potential hemolysis 3

Second-Line Laboratory Tests

Immune-Mediated Thrombocytopenia Evaluation

• HIV and HCV serologic testing regardless of risk factors, as these infections can cause thrombocytopenia indistinguishable from primary ITP 1
• Helicobacter pylori testing (urea breath test or stool antigen test preferred) in adults with typical ITP 1
• Blood group Rh(D) typing if anti-D immunoglobulin therapy is being considered 1
• Drug-dependent platelet antibody testing for suspected drug-induced immune thrombocytopenia (DITP), using serum or citrate samples (avoid EDTA) 1

Bone Marrow Assessment

• Bone marrow examination (aspirate and biopsy) with flow cytometry and cytogenetic testing in patients over 60 years, those with systemic symptoms, abnormal signs, or when splenectomy is considered 1

Additional Testing Based on Clinical Presentation

• LDH, haptoglobin, and indirect bilirubin to assess for hemolysis 3
• Direct Coombs test to rule out immune-mediated hemolysis 3
• Serum creatinine, BUN, and electrolytes to evaluate renal function 3
• Liver function tests to assess for hepatic disease 2, 4
• Antiphospholipid antibodies (not routine, but indicated if symptoms of antiphospholipid syndrome are present) 1

Specialized Testing for Specific Conditions

For Suspected Inherited Platelet Function Disorders

• Light transmission aggregometry (LTA) using epinephrine, ADP, collagen, arachidonic acid, and ristocetin 1
• Flow cytometry to assess platelet surface glycoproteins (GPIIb/IIIa, GPIIIa, GPIb, GPIb/IX) 1, 5
• Granule release assays to evaluate α-granule and δ-granule secretion 1, 5

For Suspected Thrombotic Microangiopathies

• ADAMTS13 activity for suspected thrombotic thrombocytopenic purpura (TTP) 3
• Complement studies for suspected atypical hemolytic uremic syndrome (aHUS) 3

Tests of Limited Utility

• Antiplatelet antibody assays are not routinely recommended as platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia 1
• Antinuclear antibody (ANA) testing has limited utility unless systemic lupus erythematosus is suspected 1

Important Considerations

• Collect blood samples for drug-dependent antibody testing during acute thrombocytopenia or within 3 weeks of the event 1
• Avoid EDTA tubes for platelet antibody testing as it can cause glycoprotein complex dissociation 1
• When pseudothrombocytopenia is suspected, collect blood in tubes containing heparin or sodium citrate and repeat the platelet count 2
• Distinguish between acute and chronic thrombocytopenia by reviewing previous platelet counts 2

Clinical Pitfalls to Avoid

• Don't assume all isolated thrombocytopenias are immune thrombocytopenia without appropriate exclusion of other causes 2, 4
• Don't delay evaluation of severe thrombocytopenia (<10 × 10³/μL) as it constitutes a hematologic emergency with high risk of serious bleeding 2, 4
• Remember that some conditions like heparin-induced thrombocytopenia, antiphospholipid syndrome, and thrombotic microangiopathies can present with both thrombocytopenia and thrombosis 2