Diagnosis of Heparin-Induced Thrombocytopenia
When HIT is suspected, immediately calculate the 4T score to determine pre-test probability, stop all heparin exposure (including flushes and heparin-coated catheters), order anti-PF4 antibody testing, and start therapeutic-dose alternative anticoagulation without waiting for laboratory results if the 4T score is intermediate (4-5) or high (≥6). 1, 2
Immediate Clinical Assessment: The 4T Score
The 4T score is your first diagnostic tool and determines your immediate management pathway 1, 3:
- Thrombocytopenia: Platelet fall >50% and nadir ≥20,000/μL (2 points); fall 30-50% or nadir 10,000-19,000/μL (1 point); fall <30% or nadir <10,000/μL (0 points) 1
- Timing: Platelet fall day 5-10, or ≤1 day if recent heparin exposure (2 points); consistent with days 5-10 but unclear, or >10 days (1 point); platelet fall <4 days without recent exposure (0 points) 1
- Thrombosis or other sequelae: New thrombosis, skin necrosis, or acute systemic reaction (2 points); progressive/recurrent thrombosis or erythematous skin lesions (1 point); none (0 points) 1
- Other causes of thrombocytopenia: None apparent (2 points); possible (1 point); definite (0 points) 1
Management Based on 4T Score
Low Probability (Score ≤3)
- HIT is excluded - continue heparin with close platelet monitoring every 2-3 days 1, 2
- Pursue alternative causes of thrombocytopenia 3
- No need for anti-PF4 antibody testing unless clinical picture changes 1
Intermediate Probability (Score 4-5)
- Stop all heparin immediately (including IV flushes, subcutaneous prophylaxis, and heparin-coated catheters) 1, 2, 3
- Start therapeutic-dose alternative anticoagulation without waiting for test results 1, 2
- Order anti-PF4 antibody testing (ELISA or chemiluminescent assay) 1, 3
- If anti-PF4 antibodies are positive, proceed to functional testing (serotonin release assay or HIPA test) for confirmation 2, 3
- If anti-PF4 antibodies are negative, HIT is excluded and heparin can be resumed with close monitoring 2
High Probability (Score ≥6)
- Stop all heparin immediately 1, 2, 3
- Start therapeutic-dose alternative anticoagulation immediately - do not wait for laboratory confirmation 1, 2
- Order anti-PF4 antibody testing, but treatment should not be delayed 1, 3
- Proceed to functional testing if anti-PF4 antibodies are positive 2, 3
Laboratory Testing Strategy
Initial Test: Anti-PF4 Antibodies
- Order immunoassay (ELISA or chemiluminescent test) as the first laboratory test 3
- These tests have high sensitivity and negative predictive value but lower specificity 2, 4
- A negative result effectively excludes HIT in patients with intermediate probability 2
Confirmatory Test: Functional Assays
- If anti-PF4 antibodies are positive with intermediate or high 4T score, perform functional testing 2, 3
- Options include serotonin release assay (SRA) or heparin-induced platelet activation (HIPA) test 2, 3
- These tests detect platelet-activating antibodies and have higher specificity 4, 5
Special Diagnostic Considerations
Post-Cardiac Surgery Patients
- The 4T score is less reliable in this population 2
- Look for a "biphasic" platelet count pattern - initial postoperative drop followed by recovery, then a second drop - which strongly suggests HIT 2
Patients with Recent Heparin Exposure (Within 100 Days)
- Obtain baseline platelet count before starting heparin 6
- Repeat platelet count 24 hours later if feasible, as rapid-onset HIT can occur within 24 hours in patients with circulating HIT antibodies 6
Acute Systemic Reactions
- If a patient develops fever, chills, hypertension, tachycardia, dyspnea, chest pain, or cardiopulmonary symptoms within 30 minutes of an IV heparin bolus, immediately check platelet count 6
- This presentation is strongly suggestive of acute HIT 6
Critical Pitfalls to Avoid
- Never delay stopping heparin while waiting for antibody test results if clinical probability is intermediate or high - the thrombotic risk is immediate with 30-50% of untreated patients developing thrombosis 1, 2, 7
- Do not rely solely on laboratory tests - HIT is primarily a clinical diagnosis that must be confirmed by testing, but treatment decisions are based on clinical probability 4, 5
- Remember that antibody formation alone is not diagnostic - anti-PF4 antibodies occur in many clinical settings without causing thrombocytopenia or thrombosis 7, 8
- Do not use low molecular weight heparin (LMWH) as an alternative - it cross-reacts with HIT antibodies in 80-90% of cases 1, 9
- Biological confirmation should never delay treatment - if clinical suspicion is high, act immediately 2
Monitoring During Diagnostic Workup
- Check platelet counts every 2-3 days until recovery (>150,000/μL or return to baseline) 3
- Obtain baseline coagulation studies (aPTT, INR) before starting alternative anticoagulation 3
- Monitor for new thrombotic events, as thrombosis may be the initial presentation even without significant thrombocytopenia 10, 5