What is the workup for an adult patient with no significant past medical history presenting with thrombocytopenia (low platelet count)?

Workup for Thrombocytopenia in Adults

The initial workup for thrombocytopenia requires a complete blood count with differential and peripheral blood smear examination to confirm true thrombocytopenia and exclude pseudothrombocytopenia, followed by targeted testing based on clinical presentation and severity. 1, 2

Immediate First Steps

Confirm True Thrombocytopenia

• Repeat the platelet count using a heparin or sodium citrate tube to exclude pseudothrombocytopenia, which occurs in approximately 0.1% of adults due to platelet clumping in EDTA tubes 3, 4
• Examine the peripheral blood smear immediately to assess platelet morphology, size, and identify platelet clumping 1, 2

Essential Initial Laboratory Tests

• Complete blood count with differential to assess for other cytopenias (anemia, leukopenia) that narrow the differential diagnosis 1, 2
• Peripheral blood smear examination to identify abnormal cells, assess platelet size/structure, and exclude alternative diagnoses 1, 2
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) to assess coagulation function 2
• D-dimer and fibrinogen assay to rule out disseminated intravascular coagulation (DIC) 2, 3
• Liver function tests to exclude liver disease as a causative factor 2
• Chemistry profile to assess renal function and nutritional status 2

Clinical Context Assessment

Obtain Detailed History

• Medication history including heparin, quinidine, sulfonamides, GPIIb-IIIa inhibitors, chemotherapy agents, and over-the-counter medications that can cause drug-induced thrombocytopenia 3, 5
• Bleeding symptoms including petechiae, purpura, ecchymosis, mucosal bleeding (epistaxis, gingival bleeding), menorrhagia, and severity of hemorrhage 3, 4
• Duration of thrombocytopenia by reviewing previous platelet counts to distinguish acute from chronic thrombocytopenia 4
• HIV risk factors as HIV infection can cause thrombocytopenia 1, 2
• Family history of bleeding disorders or thrombocytopenia to assess for inherited conditions 3

Physical Examination Findings

• Assess for splenomegaly on physical examination; if suspected, obtain abdominal CT scan or ultrasound 1
• Evaluate for signs of liver disease (jaundice, ascites, spider angiomas) 5
• Look for signs of systemic illness or infection 5

Risk-Stratified Additional Testing

For Patients with Isolated Thrombocytopenia (No Other Cytopenias)

The most likely diagnoses are immune thrombocytopenic purpura (ITP), drug-induced thrombocytopenia, or pseudothrombocytopenia 5, 4

• HIV testing should be performed in patients with risk factors 1, 2
• Antiplatelet antibody testing if immune thrombocytopenia is suspected, though this is not required for diagnosis 2, 3
• Bone marrow aspiration and biopsy should be performed in patients with persistent thrombocytopenia lasting more than 6-12 months or those unresponsive to intravenous immunoglobulin (IVIg), but is not required before initiating IVIg therapy 1, 3

For Patients with Thrombocytopenia Plus Other Cytopenias

This suggests bone marrow pathology, requiring more extensive evaluation 2

• Bone marrow aspiration and biopsy should not be delayed, especially if abnormal cells are seen in peripheral blood or if no obvious cause is identified from initial testing 2
• Flow cytometry of peripheral blood and/or bone marrow to identify leukemia or lymphoma 2
• Cytogenetic analysis and molecular studies including FISH, RT-PCR, and next-generation sequencing to detect genetic abnormalities associated with leukemia 2

For Patients with Thrombocytopenia Plus Thrombosis

This paradoxical presentation requires specific testing 3

• Calculate the 4T score (0-2 points each for thrombocytopenia severity, timing, thrombosis, and other causes) to assess probability of heparin-induced thrombocytopenia (HIT) 3
• HIT antibody testing if 4T score suggests intermediate or high probability 3
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies) to evaluate for antiphospholipid syndrome 3
• ADAMTS13 activity level to evaluate for thrombotic thrombocytopenic purpura (TTP) 3

For Progressive or Severe Unexplained Thrombocytopenia

When platelet count is <50,000/mm³ without clear etiology 1

• Workup for autoimmune disease including ANA, complement levels, and other autoimmune markers 1
• Rule out DIC with D-dimer, fibrinogen, PT/aPTT, and peripheral smear for schistocytes 1, 2
• Evaluate for immune-mediated thrombocytopenia if precipitous development occurs 1

For Pregnant Patients

• Blood pressure measurement to rule out preeclampsia 1
• Liver function tests to assess for HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) 1
• HIV testing if risk factors present 1

Common Pitfalls to Avoid

• Do not assume pseudothrombocytopenia has been excluded until blood is redrawn in heparin or sodium citrate tube 3, 4
• Do not assume leukopenia and thrombocytopenia are always due to the same cause, as multiple pathologies may coexist 2
• Do not delay bone marrow examination in patients with unexplained cytopenias when clinical suspicion for malignancy is high 2
• Do not routinely perform bone marrow biopsy before initiating IVIg therapy in suspected ITP 1
• Do not overlook medication-induced thrombocytopenia, as this is a common and reversible cause 3, 5

Severity-Based Urgency

• Platelet count >50,000/μL: Patients are generally asymptomatic; outpatient workup is appropriate 5, 4
• Platelet count 20,000-50,000/μL: May have mild skin manifestations; expedited outpatient evaluation with hematology follow-up within 24-72 hours 1, 4
• Platelet count 10,000-20,000/μL: Increased bleeding risk with minimal trauma; consider hospitalization if significant mucosal bleeding or comorbidities 1, 4
• Platelet count <10,000/μL: High risk of spontaneous bleeding; constitutes a hematologic emergency requiring immediate hospitalization and urgent evaluation 1, 4