What is the workup for thrombocytopenia (low platelet count)?

Diagnostic Approach to Thrombocytopenia

The workup for thrombocytopenia should begin with confirmation of true thrombocytopenia through peripheral blood smear examination, followed by a systematic evaluation of potential causes including decreased production, increased destruction, sequestration, or dilution of platelets. 1

Initial Evaluation

Confirm True Thrombocytopenia

• Examine peripheral blood smear to distinguish true thrombocytopenia from pseudothrombocytopenia (which occurs in about 0.1% of adults due to platelet clumping in EDTA) 2
• If pseudothrombocytopenia is suspected, collect blood in a tube containing heparin or sodium citrate and repeat the platelet count 3

Essential Laboratory Tests

• Complete blood count with differential to confirm thrombocytopenia and evaluate other cell lines 1
• Coagulation studies including prothrombin time and activated partial thromboplastin time 1
• Review of previous platelet counts to distinguish acute from chronic thrombocytopenia 3

History and Physical Examination Focus

Key History Elements

• Bleeding symptoms (type, severity, duration) 2
• Medication use, especially heparin, quinidine/quinine, sulfonamides, alcohol, and other drugs associated with thrombocytopenia 2
• Recent transfusions 2
• Family history of thrombocytopenia 2
• Risk factors for HIV infection 2
• Comorbid conditions that may increase bleeding risk 2
• Recent surgeries, pregnancies, or hemostatic challenges 2

Physical Examination Focus

• Assess for bleeding signs (petechiae, purpura, ecchymosis, mucosal bleeding) 2
• Evaluate for hepatosplenomegaly and lymphadenopathy (splenomegaly suggests against ITP) 2
• Check for signs of infection, particularly HIV 2
• Look for evidence of autoimmune disorders (arthritis, skin rash, alopecia) 2
• Neurologic examination and funduscopic examination to establish baseline 2

Diagnostic Algorithm Based on Platelet Count

Severe Thrombocytopenia (<20 × 10⁹/L)

• Consider hospital admission for newly diagnosed patients 2
• For established diagnosis with no significant bleeding, outpatient management may be appropriate 2
• Evaluate for emergent causes requiring immediate intervention:
  • Heparin-induced thrombocytopenia (use 4T score) 2
  • Thrombotic microangiopathies 3
  • DIC (disseminated intravascular coagulation) 2

Moderate Thrombocytopenia (20-50 × 10⁹/L)

• Outpatient management is generally appropriate in the absence of significant bleeding 2
• Ensure expedited follow-up with a hematologist within 24-72 hours 2

Mild Thrombocytopenia (>50 × 10⁹/L)

• Generally asymptomatic; spontaneous serious bleeding is rare (<5% of patients) 2, 3
• Outpatient management with appropriate follow-up 2

Specialized Testing Based on Clinical Suspicion

For Suspected Immune Thrombocytopenia (ITP)

• HIV testing (HIV infection commonly associated with thrombocytopenia) 2, 1
• Consider bone marrow examination for:
  • Persistent thrombocytopenia (>6-12 months) 2
  • Patients unresponsive to initial therapy 2
  • Atypical features suggesting alternative diagnosis 2

For Suspected Heparin-Induced Thrombocytopenia

• Apply 4T score based on:
  • Degree of thrombocytopenia
  • Timing of platelet count fall
  • Presence of thrombosis
  • Other potential causes of thrombocytopenia 2

For Suspected Splenic Sequestration

• Abdominal ultrasound or CT scan to evaluate spleen size 2

Common Pitfalls to Avoid

• Failing to confirm true thrombocytopenia through peripheral blood smear examination 1
• Overlooking medication-induced thrombocytopenia (especially heparin, quinidine, sulfonamides) 2
• Performing unnecessary bone marrow examination before initiating therapy in typical cases 2
• Missing the diagnosis of heparin-induced thrombocytopenia, which can cause both thrombocytopenia and thrombosis 2
• Failing to recognize the dynamic pattern of platelet count changes, which can provide diagnostic clues (e.g., abrupt decrease 1-2 weeks after surgery suggests immunologic causes) 4

Special Considerations

• In pregnancy, measure blood pressure to rule out preeclampsia and perform liver function tests 2
• In ICU patients, consider the timing and pattern of platelet count decline:
  • Gradual decline over 5-7 days suggests consumptive coagulopathy or bone marrow failure
  • Abrupt decrease within 1-2 days after initial increase suggests immune-mediated causes 4
• For patients with both thrombocytopenia and thrombosis, consider antiphospholipid syndrome, heparin-induced thrombocytopenia, or thrombotic microangiopathies 3