What is the initial blood workup for a patient with suspected Immune Thrombocytopenic Purpura (ITP)?

Initial Blood Workup for Suspected ITP

The initial workup for suspected ITP requires a complete blood count with peripheral blood smear examination by a qualified hematologist or pathologist, HIV and hepatitis C testing in all adults, and exclusion of pseudothrombocytopenia—bone marrow examination is not routinely necessary in patients with typical features. 1, 2

Mandatory First-Line Tests

Complete Blood Count and Peripheral Smear

• Obtain a CBC to confirm isolated thrombocytopenia (platelet count <100 × 10⁹/L) with otherwise normal hemoglobin and white blood cell parameters. 1, 2, 3
• Request manual peripheral blood smear examination by a qualified hematologist or pathologist—this is paramount to diagnosis and cannot be skipped. 1, 2
• The smear must show normal-sized or slightly enlarged platelets (not giant platelets approaching RBC size), normal RBC morphology without schistocytes, and normal WBC morphology without immature cells. 1, 3
• Repeat the platelet count using a different anticoagulant (non-EDTA) to definitively exclude pseudothrombocytopenia, which occurs in 0.1% of adults due to EDTA-induced platelet clumping. 2

Mandatory Infectious Disease Screening

• Test all adults with suspected ITP for HIV and hepatitis C virus, regardless of risk factors or local prevalence—these infections are clinically indistinguishable from primary ITP and may precede other symptoms by years. 1, 2, 3
• Consider H. pylori testing (preferably urea breath test or stool antigen test) in adults where eradication therapy would be used if positive. 1, 2

Basic Coagulation Studies

• Obtain PT, aPTT, and fibrinogen to exclude coagulopathy and disseminated intravascular coagulation. 2
• Measure D-dimer if thrombosis is suspected or if there is recent vaccination history (within 5-42 days), as levels >4000 μg/mL support vaccine-induced immune thrombocytopenia and thrombosis (VITT). 1, 2

Essential Clinical Assessment

History Red Flags

• Perform thorough medication review for heparin, quinidine/quinine, sulfonamides, vancomycin, alcohol, aspirin, and NSAIDs—drug-induced thrombocytopenia is common and reversible. 2
• Document vaccination history within the past 5-42 days to assess for VITT. 1, 2
• Ask about constitutional symptoms (fever, weight loss, bone pain) which suggest secondary causes like lymphoproliferative disease or SLE. 1, 2
• Obtain family history of thrombocytopenia or bleeding disorders to identify inherited thrombocytopenias. 2

Physical Examination Findings

• Physical examination should be normal except for bleeding manifestations (petechiae, purpura, mucosal bleeding)—any deviation requires further investigation. 1, 2
• The presence of splenomegaly, hepatomegaly, or lymphadenopathy excludes primary ITP and mandates investigation for secondary causes. 1, 2, 3

Additional Testing Based on Context

When Recent Vaccination (5-42 days)

• Measure D-dimer immediately—levels >4000 μg/mL are highly suggestive of VITT. 1, 2
• Perform anti-PF4 antibody ELISA if VITT is suspected based on thrombocytopenia, thrombosis, and elevated D-dimer. 1, 2
• Obtain same-day imaging (head CT venogram, abdominal ultrasound, CT pulmonary angiography) based on symptoms to identify thrombosis. 1

Additional Considerations

• Pregnancy test in women of childbearing age. 2
• Blood group Rh(D) typing if anti-D immunoglobulin therapy is being considered. 1
• Liver function tests for patients with risk factors for liver disease. 2

When Bone Marrow Examination IS Required

Bone marrow examination is NOT routinely necessary in typical ITP but is mandatory in the following situations: 1, 2, 3

• Age ≥60 years (to exclude myelodysplastic syndromes, leukemias, or other malignancies). 1, 2
• Systemic symptoms present (fever, weight loss, bone pain). 1, 2
• Abnormal blood count parameters beyond isolated thrombocytopenia (anemia disproportionate to bleeding, leukopenia, leukocytosis). 1, 2
• Atypical peripheral smear findings (schistocytes, leukocyte inclusion bodies, excessive giant platelets). 1, 2
• Minimal or no response to first-line ITP therapies. 2

Tests NOT Recommended

• Platelet-associated IgG and glycoprotein-specific antibody testing are not routinely recommended—they are elevated in both immune and non-immune thrombocytopenia and do not change management. 1, 3
• Antiphospholipid antibodies and antinuclear antibodies are not routinely indicated unless symptoms of antiphospholipid syndrome or SLE are present. 1

Critical Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear—automated counts miss pseudothrombocytopenia, giant platelets, and schistocytes. 2, 3
• Never skip HIV and HCV testing in adults, even without apparent risk factors. 1, 2, 3
• Do not assume elevated immature platelet fraction (IPF) confirms ITP—severe ITP can present with low IPF, necessitating bone marrow examination in atypical cases. 2, 4
• Do not overlook drug-induced thrombocytopenia, which is common and reversible with medication discontinuation. 2
• Do not miss VITT—assess recent vaccination history and maintain high suspicion for thrombosis. 1, 2