What investigations should be sent for a patient with thrombosis and severe thrombocytopenia?

Investigations for Thrombosis with Severe Thrombocytopenia

For a patient with thrombosis and severe thrombocytopenia, a comprehensive diagnostic workup should include full blood count, coagulation studies, D-dimer, anti-PF4 antibodies, and appropriate imaging to confirm thrombosis location. 1

Initial Laboratory Investigations

• Complete blood count with peripheral blood smear - To confirm thrombocytopenia and examine for abnormal platelet morphology, giant platelets, or other cell line abnormalities
• D-dimer measurement - Critical test, with values >4000 μg/mL (FEU) being highly suspicious for VITT
• Coagulation screen - Including:
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Clauss fibrinogen assay
  • Fibrin monomers
• Anti-PF4 antibodies by ELISA - Essential for diagnosing VITT or HIT
• Blood film examination - To confirm true thrombocytopenia and exclude pseudothrombocytopenia

Imaging Studies

• Site-specific imaging based on symptoms:
  • Head CT venogram or MR angiography for suspected cerebral venous sinus thrombosis
  • Abdominal ultrasound or venogram for portal or splanchnic vein thrombosis
  • CT pulmonary angiography for suspected pulmonary embolism
  • Doppler ultrasound of extremities for deep vein thrombosis
  • Consider systematic ultrasound screening of lower limbs even in asymptomatic patients 1

Clinical Assessment and Risk Stratification

• Vaccination history - Document any COVID-19 or other vaccination within the past 42 days 1
• Medication history - Particularly heparin exposure within the past 100 days 1
• 4T score calculation for suspected HIT, assessing:
  1. Thrombocytopenia severity (drop >50% or nadir 20-100×10^9/L)
  2. Timing of platelet count fall (5-10 days after heparin initiation)
  3. Thrombosis presence
  4. Other causes of thrombocytopenia 1

Special Considerations

For Suspected VITT

• Onset typically 5-30 days post-COVID-19 vaccination (or up to 42 days if isolated DVT/PE)
• Thrombocytopenia (platelet count <150×10^9/L)
• D-dimer >4000 μg/mL (FEU) is highly suggestive
• Positive anti-PF4 antibodies by ELISA 1

For Suspected HIT

• Examine for "biphasic" evolution profile of platelet count in post-cardiac surgery patients
• Consider immunological tests that specifically detect IgG antibodies against PF4 1

Pitfalls to Avoid

1. Don't delay imaging in patients with high clinical suspicion - perform same-day imaging to confirm thrombosis location
2. Don't miss normal platelet count VITT - approximately 5% of patients with VITT have normal platelet counts at presentation that subsequently fall 1
3. Don't rely solely on rapid immunoassays for anti-PF4 - ELISA tests have better sensitivity
4. Don't forget to repeat platelet counts after 2-3 days if clinical suspicion remains high despite initial normal count 1
5. Don't overlook alternative diagnoses - consider other causes of thrombocytopenia with thrombosis such as antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and DIC 1, 2

This diagnostic approach allows for rapid identification of potentially life-threatening conditions like VITT or HIT, enabling prompt initiation of appropriate treatment to reduce morbidity and mortality.