What labs are used to determine the etiology of thrombocytopenia?

Laboratory Evaluation to Determine Etiology of Thrombocytopenia

The initial laboratory workup for thrombocytopenia should include a complete blood count with differential and peripheral blood smear to exclude pseudothrombocytopenia and distinguish isolated thrombocytopenia from pancytopenia, followed by targeted testing based on clinical context including HIV, hepatitis C, H. pylori, and drug-dependent antibody testing when indicated. 1, 2

Initial Essential Laboratory Tests

First-Line Testing

• Complete blood count (CBC) with differential is mandatory to identify whether thrombocytopenia is isolated or part of pancytopenia, which fundamentally changes the differential diagnosis toward bone marrow failure or infiltration 1, 2

• Peripheral blood smear examination must be performed immediately to exclude pseudothrombocytopenia caused by EDTA-dependent platelet agglutination, which can falsely lower platelet counts 1, 2, 3

  • If pseudothrombocytopenia is suspected, repeat the platelet count using heparin or sodium citrate tubes instead of EDTA 2, 3
  • The smear also identifies platelet morphology abnormalities, abnormal white cells, red cell fragments, and schistocytes 1, 2

• Basic coagulation studies including PT, aPTT, fibrinogen, and D-dimers should be obtained to evaluate for disseminated intravascular coagulation (DIC), which can occur in severe cases and does not exclude other diagnoses like heparin-induced thrombocytopenia 4

Etiology-Specific Laboratory Testing

For Drug-Induced Thrombocytopenia

• Drug-dependent platelet antibody testing requires specialized immunoassays demonstrating drug-dependence, immunoglobulin binding to platelets, and platelet specificity 4
  • Blood samples should be collected during the acute thrombocytopenic episode, or within 3 weeks of the event, as antibodies disappear rapidly 4
  • Use clotted serum or citrate samples; avoid EDTA as it causes glycoprotein complex dissociation 4

For Heparin-Induced Thrombocytopenia (HIT)

• Anti-PF4 antibodies should be tested immediately when clinical probability is intermediate or high based on the 4T score 4
  • Immunological tests (ELISA or chemiluminescent) detect IgG, IgM, IgA antibodies against modified PF4 with excellent sensitivity and negative predictive value 4
  • Specificity improves when using IgG-specific methods with quantitative results (absorbance values) 4
  • After cardiac surgery, anti-PF4 antibodies appear in nearly 50% of patients without HIT, reducing specificity 4

For Immune Thrombocytopenia (ITP)

• Infectious disease screening should include HIV, hepatitis C, and H. pylori testing in all adults with suspected ITP 1, 2

  • These infections can cause secondary immune thrombocytopenia with different natural histories and treatment responses 1, 2

• Immunoglobulin measurement may be considered to exclude common variable immune deficiency (CVID), as ITP can be a presenting feature 1, 2

• Antiplatelet antibody testing includes measurement of platelet-associated immunoglobulins, circulating antibodies reacting with platelets, and antigen-specific antibodies against platelet glycoproteins 5

For Distinguishing Production vs. Destruction Disorders

• Immature platelet fraction (IPF%) provides an indirect measure of bone marrow thrombopoietic function 5, 6

  • Significantly elevated IPF% indicates increased platelet consumption (median 9.55%) or ITP (median 13.4%) compared to controls (median 4.2%) 6
  • Normal or slightly elevated IPF% suggests hypoproductive thrombocytopenia from impaired bone marrow production 5, 6

• Plasma soluble glycocalicin measurement evaluates platelet turnover rate 5

  • Normal or increased levels occur in immune thrombocytopenia 5
  • Decreased levels indicate hypoproductive thrombocytopenia 5

When to Perform Bone Marrow Examination

• Bone marrow examination is indicated for patients over 60 years, those with atypical features not consistent with ITP, or when systemic symptoms suggest underlying malignancy or myelodysplasia 1, 2

• Bone marrow examination is NOT necessary in patients with typical features of ITP, including isolated thrombocytopenia with normal hemoglobin, white blood cell count, and white cell morphology 1, 2

Red Flags Requiring Additional Investigation

The following findings suggest alternative diagnoses and mandate expanded testing 1, 2:

• Splenomegaly, hepatomegaly, or lymphadenopathy
• Abnormal hemoglobin level, white blood cell count, or white cell morphology
• Non-petechial rash
• Constitutional symptoms (fever, weight loss)

Common Pitfalls to Avoid

• Failing to exclude pseudothrombocytopenia by examining the blood smear for platelet clumps before pursuing extensive workup 1, 2, 3

• Missing drug-induced thrombocytopenia by not obtaining a detailed medication history including over-the-counter drugs, herbal supplements, and recent medication changes 1

• Delaying sample collection for drug-dependent antibody testing beyond 3 weeks after the acute episode, when antibody levels have declined 4

• Not recognizing secondary causes of ITP (autoimmune disorders, viral infections, lymphoproliferative disorders) which have different treatment responses 1, 2