What labs should be ordered for a patient presenting with thrombocytopenia (low platelet count)?

Laboratory Workup for Thrombocytopenia

Order a complete blood count with differential and peripheral blood smear examination immediately to confirm true thrombocytopenia and exclude pseudothrombocytopenia, followed by risk-stratified testing based on clinical presentation. 1

Essential First-Line Tests

Immediate Confirmation Tests

• Complete blood count (CBC) with differential to assess for other cytopenias (anemia, leukopenia) that narrow the differential diagnosis 1
• Peripheral blood smear examination to confirm true thrombocytopenia, assess platelet morphology and size, identify platelet clumping (pseudothrombocytopenia occurs in ~0.1% of adults due to EDTA-induced agglutination), and evaluate red and white blood cell morphology 2, 1

Critical pitfall: If pseudothrombocytopenia is suspected, immediately redraw blood in a heparin or sodium citrate tube and repeat the platelet count 3. This prevents unnecessary workup and treatment.

Blood Smear Findings Guide Further Testing

Findings consistent with ITP (isolated thrombocytopenia): 2

• Platelets normal or larger than normal (but not giant)
• Normal red blood cell morphology
• Normal white blood cell morphology

Findings suggesting alternative diagnoses requiring urgent evaluation: 2

• Red blood cell schistocytes or poikilocytosis → consider thrombotic microangiopathy (TTP, HUS)
• Giant platelets approaching red blood cell size → consider Bernard-Soulier syndrome
• Leukocytosis/leukopenia with immature cells → consider bone marrow disorder

Risk-Stratified Additional Testing

For All Patients with Confirmed Thrombocytopenia

• Detailed medication history including heparin, quinidine, sulfonamides, GPIIb-IIIa inhibitors, chemotherapy, NSAIDs, and over-the-counter medications 2, 1
• HIV testing if risk factors present (HIV commonly associated with thrombocytopenia) 2, 1

For Suspected Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)

If onset 5-30 days post COVID-19 vaccine: 2

• D-dimer measurement (>4000 μg/mL FEU supports diagnosis)
• Coagulation screen including Clauss fibrinogen assay
• Anti-PF4 antibody ELISA assay
• Imaging based on symptoms (head CT venogram for suspected CVST, abdominal ultrasound for splanchnic thrombosis, CT pulmonary angiography for PE)

For Suspected Thrombotic Microangiopathy

If schistocytes present or acute renal/neurologic abnormalities: 2

• Coagulation studies including fibrinogen
• Renal function tests (creatinine, BUN)
• Lactate dehydrogenase (LDH)
• Direct antiglobulin test (Coombs)
• ADAMTS13 activity if TTP suspected

Tests of Uncertain Routine Value (Use Selectively)

The American Society of Hematology panel identified these as uncertain for routine use at presentation: 2

• ANA, direct antiglobulin test, lupus anticoagulant/antiphospholipid antibodies
• Chemistry profile, coagulation studies (unless bleeding or pre-procedure)
• Chest x-ray
• Bone marrow examination (reserve for specific indications below)

When to Order Bone Marrow Examination

Bone marrow aspiration and biopsy are indicated for: 1

• Persistent thrombocytopenia lasting >6-12 months
• Patients unresponsive to intravenous immunoglobulin (IVIg)
• Atypical presenting features suggesting alternative diagnosis
• Before splenectomy (though appropriateness is uncertain per guidelines) 2

Not routinely indicated: For typical ITP presentation with isolated thrombocytopenia and normal blood smear 2

Specialized Testing for Inherited Platelet Disorders

Only pursue if clinical history suggests inherited disorder (bleeding from early childhood, family history): 4

• Flow cytometry using antibodies against GPIIb/IIIa (CD41), GPIIIa (CD61), GPIb (CD42b), GPIb/IX (CD42a)
• Light transmission aggregometry (LTA) with standard agonists (ADP, collagen, epinephrine, ristocetin)
• Granule release assessment (α and δ granules)

Urgency-Based Laboratory Priorities

Platelet count <10,000/μL (hematologic emergency): 1

• Immediate CBC confirmation, peripheral smear, coagulation studies
• Urgent hematology consultation

Platelet count 10,000-50,000/μL: 1, 3

• Same-day CBC confirmation and peripheral smear
• Risk-stratified additional testing based on clinical presentation

Platelet count 50,000-100,000/μL: 3

• Outpatient evaluation acceptable if asymptomatic
• Confirm with repeat CBC and peripheral smear

Tests to Avoid

Do not routinely order: 2

• Platelet-associated IgG assay (unnecessary and inappropriate)
• Platelet antigen-specific antibody assays
• Platelet survival studies
• Serum complement levels (unless refractory disease)
• Bleeding time (insufficient specificity and sensitivity) 4