Thrombocytopenia Workup
Initial Diagnostic Evaluation
Begin with a complete blood count (CBC) with peripheral blood smear to confirm true thrombocytopenia and exclude pseudothrombocytopenia, which accounts for a significant proportion of apparent low platelet counts. 1, 2
Essential First-Line Laboratory Tests
- Repeat platelet count in heparin or sodium citrate tube to exclude EDTA-dependent pseudothrombocytopenia before proceeding with further workup 3, 4
- Peripheral blood smear review to assess for platelet clumping, schistocytes (suggesting thrombotic microangiopathy), abnormal white blood cells, or other morphologic abnormalities 3, 4
- HIV and Hepatitis C testing should be performed urgently, as these are common secondary causes of immune thrombocytopenia 1, 2
- Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I) to evaluate for antiphospholipid syndrome 1, 2
- Comprehensive metabolic panel to assess for liver or renal impairment that may contribute to bleeding risk 1
- Helicobacter pylori testing should be considered, with eradication therapy if positive 2
Medication Review
- Conduct thorough medication history focusing on heparin products (including flushes), antiplatelet agents, NSAIDs, quinine-containing products, and other drugs known to cause thrombocytopenia 1, 2
- For patients with recent heparin exposure and platelet count drop >50% within 5-10 days, immediately suspect heparin-induced thrombocytopenia (HIT) and discontinue all heparin products 2, 5
Risk Stratification Based on Platelet Count
Platelet Count ≥50,000/μL
- Patients are generally asymptomatic and rarely require treatment unless active bleeding, platelet dysfunction, planned surgery, or mandatory anticoagulation is present 1, 3
- No activity restrictions necessary at this level 1
- Full therapeutic anticoagulation can be safely administered without dose modification 1, 6
Platelet Count 30,000-50,000/μL
- Patients may develop mild skin manifestations (petechiae, purpura, ecchymosis) but severe bleeding is uncommon 3, 7
- Treatment is not routinely required unless significant mucous membrane bleeding is present 1
- For patients requiring anticoagulation, reduce LMWH to 50% of therapeutic dose or use prophylactic dosing 1, 6
Platelet Count <30,000/μL with Bleeding
- Immediate treatment is indicated with corticosteroids (prednisone 1-2 mg/kg/day for maximum 14 days) 1, 2
- Add intravenous immunoglobulin (IVIg 0.8-1 g/kg single dose) if bleeding is life-threatening or involves the central nervous system 1
- Platelet transfusion should be given in combination with IVIg for active CNS, gastrointestinal, or genitourinary bleeding 1
Platelet Count <10,000/μL
- High risk of serious spontaneous bleeding exists at this level 3, 7
- Prophylactic platelet transfusion is recommended for stable patients 1
- Consider hospitalization if platelet count drops below 20,000/μL or bleeding intensifies 1
Distinguishing Acute vs. Chronic Thrombocytopenia
- Review previous platelet counts to determine if thrombocytopenia is acute (requiring potential hospitalization) or chronic 3, 4
- Acute thrombocytopenia with systemic illness requires immediate evaluation for life-threatening causes: HIT, thrombotic microangiopathies (TTP/HUS), HELLP syndrome, or disseminated intravascular coagulation 3, 4
- Isolated thrombocytopenia without systemic illness most likely represents immune thrombocytopenia (ITP) or drug-induced thrombocytopenia 3, 4
When to Consider Bone Marrow Aspiration
- Bone marrow examination is NOT routinely required for diagnosis of ITP 1, 2
- Consider bone marrow aspiration only if:
Monitoring Strategy
- Weekly platelet count monitoring during dose adjustment phase of any treatment 1, 2
- Monthly monitoring following establishment of stable treatment dose 2
- Weekly monitoring for at least 2 weeks following discontinuation of treatment 1
Critical Pitfalls to Avoid
- Never assume thrombocytopenia is real without excluding pseudothrombocytopenia by repeating count in different anticoagulant 3, 4
- Do not delay HIT evaluation in patients with recent heparin exposure and platelet drop, as thrombotic complications occur in 30-50% of untreated cases 2, 5
- Avoid treating based solely on platelet count without considering bleeding symptoms and clinical context 1, 7
- Do not normalize platelet counts as a treatment goal; target is ≥50,000/μL to reduce bleeding risk 1
- Never use direct oral anticoagulants (DOACs) with platelets <50,000/μL due to lack of safety data and increased bleeding risk 1, 6