What is the workup for a patient suspected of having Heparin-Induced Thrombocytopenia and Thrombosis (HITT)?

Workup for Heparin-Induced Thrombocytopenia and Thrombosis (HITT)

The workup for suspected HITT should begin with calculating the 4Ts score, followed by appropriate laboratory testing based on clinical probability, and immediate discontinuation of all heparin products with initiation of a non-heparin anticoagulant if intermediate or high probability is determined. 1

Initial Assessment: 4Ts Score Calculation

The 4Ts score is the cornerstone of initial HITT assessment and includes:

1. Thrombocytopenia

   • Fall in platelet count >50% AND nadir ≥20 G/L (2 points)
   • Fall in platelet count 30-50% OR nadir 10-19 G/L (1 point)
   • Fall in platelet count <30% OR nadir <10 G/L (0 points)

2. Timing of platelet count fall

   • Clear onset between days 5-10 OR ≤1 day if heparin exposure within past 30 days (2 points)
   • Consistent with days 5-10 fall but unclear OR onset after day 10 OR ≤1 day if heparin exposure within past 31-100 days (1 point)
   • Platelet count fall ≤4 days without recent heparin exposure (0 points)

3. Thrombosis or other sequelae

   • Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV heparin bolus (2 points)
   • Progressive or recurrent thrombosis, non-necrotizing skin lesions, or suspected thrombosis (1 point)
   • None (0 points)

4. Other causes of thrombocytopenia

   • No other apparent cause (2 points)
   • Possible other cause present (1 point)
   • Definite other cause present (0 points)

Total score interpretation:

• 0-3: Low probability
• 4-5: Intermediate probability
• 6-8: High probability

Management Based on 4Ts Score

Low Probability (4Ts score ≤3)

• Continue heparin if indicated
• No HIT laboratory testing generally needed
• Monitor platelet count
• Search for alternative causes of thrombocytopenia 1

Important caveat: Laboratory testing may still be appropriate if there is uncertainty about the 4Ts score due to missing data 1

Intermediate Probability (4Ts score 4-5)

1. Discontinue all heparin products immediately
2. Start non-heparin anticoagulant:
   • If high bleeding risk: prophylactic intensity
   • If not high bleeding risk: therapeutic intensity
3. Obtain immunoassay (anti-PF4/heparin antibody test) 1

High Probability (4Ts score ≥6)

1. Discontinue all heparin products immediately
2. Start non-heparin anticoagulant at therapeutic intensity
3. Obtain immunoassay (anti-PF4/heparin antibody test)
4. If immunoassay positive, obtain functional assay if available 1

Laboratory Testing

Immunoassay (First-line test)

• Tests for antibodies against PF4-heparin complexes
• Lower threshold ELISA preferred over high threshold
• Quantitative result (optical density) should be reported
• High negative predictive value but moderate specificity 1

Functional Assay (Second-line test)

• Serotonin Release Assay (SRA) - gold standard
• Heparin-Induced Platelet Activation (HIPA) test
• Higher specificity than immunoassays
• May not be necessary if 4Ts score is high and immunoassay is strongly positive (e.g., ELISA OD >2.0) 1

Non-Heparin Anticoagulant Options

Preferred agents:

1. Argatroban

   • Direct thrombin inhibitor
   • Initial dose: 2 mcg/kg/min continuous infusion
   • Dose adjustment based on aPTT (target 1.5-2.5× baseline)
   • Preferred in renal impairment
   • Hepatic metabolism - reduce dose in liver dysfunction 1, 2

2. Bivalirudin

   • Direct thrombin inhibitor
   • Short half-life (25 minutes)
   • Useful for procedures requiring short-acting anticoagulation 1

3. Danaparoid

   • Factor Xa inhibitor with minimal anti-IIa activity
   • Not recommended in severe renal impairment
   • Must be given at therapeutic doses, not prophylactic 1

4. Fondaparinux

   • Synthetic pentasaccharide
   • Once-daily subcutaneous administration
   • Limited data in acute HIT 1

5. Direct oral anticoagulants (DOACs)

   • Emerging option for stable patients
   • Rivaroxaban most studied for this indication 1

Additional Management Considerations

1. Avoid platelet transfusions unless life-threatening bleeding or required for invasive procedure 1

2. Avoid warfarin in acute HIT until platelet count recovers to >150 × 10^9/L 1

   • If warfarin already started, administer vitamin K

3. Inferior vena cava filters are not recommended in acute HIT 1

4. Monitor for thrombosis - approximately 50% of HIT patients develop thrombotic events

5. Duration of treatment:

   • HIT without thrombosis: minimum 4 weeks
   • HIT with thrombosis: 3-6 months 1

Common Pitfalls to Avoid

1. Delayed recognition - failure to monitor platelet counts in patients receiving heparin

2. Premature exclusion of HIT diagnosis based solely on timing - delayed-onset HIT can occur up to 3 weeks after heparin discontinuation 3

3. Initiating warfarin too early - can precipitate venous limb gangrene or warfarin-induced skin necrosis 1

4. Inadequate dosing of alternative anticoagulants - prophylactic doses are insufficient for treating established HIT 1

5. Missing data in 4Ts score calculation - when in doubt, err on the side of a higher score 1

6. Failure to recognize that both unfractionated heparin and low molecular weight heparin can cause HIT

By following this systematic approach to the workup of suspected HITT, clinicians can ensure timely diagnosis and appropriate management to reduce the risk of thrombotic complications.