Management of Heparin-Induced Thrombocytopenia (HIT)
When HIT is suspected with intermediate or high clinical probability, immediately discontinue all forms of heparin and start therapeutic-dose non-heparin anticoagulation without waiting for laboratory confirmation. 1, 2
Initial Assessment and Risk Stratification
Calculate the 4T score to determine pre-test probability: low (≤3 points), intermediate (4-5 points), or high (≥6 points) 1, 2
For low pre-test probability (4T ≤3): HIT can be excluded, continue heparin with close platelet monitoring, and pursue alternative causes of thrombocytopenia 3, 1
For intermediate pre-test probability (4T = 4-5): Stop all heparin immediately, initiate therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing 3, 1
For high pre-test probability (4T ≥6): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing—do not wait for results before treating 3, 1
In post-cardiac surgery patients, watch for a "biphasic" platelet count pattern (initial drop, recovery, then second drop), which strongly suggests HIT even when the 4T score is less reliable 1
Immediate Actions
Discontinue ALL forms of heparin including unfractionated heparin, low molecular weight heparin, heparin flushes, and heparin-coated catheters 1, 2
Start therapeutic-dose non-heparin anticoagulation immediately, even in the absence of thrombosis, due to the extremely high thrombotic risk (up to 50% develop new thrombosis) 1, 2
Do NOT give platelet transfusions, as they may paradoxically worsen thrombosis in HIT patients 1, 2
Do NOT start vitamin K antagonists (warfarin) in the acute phase, as they can cause venous limb gangrene before platelet recovery 1, 2
Alternative Anticoagulant Selection
First-Line Options by Clinical Scenario:
For patients with normal renal and hepatic function:
Argatroban: Start at 2 mcg/kg/min as continuous IV infusion, monitor aPTT to maintain 1.5-3 times baseline 1, 4
Bivalirudin: Useful for procedures requiring short-acting anticoagulation (half-life 20-30 minutes) 1
Fondaparinux: Option for stable patients, does not require specific monitoring 2
For severe renal impairment (CrCl <30 mL/min):
Argatroban is the ONLY recommended agent, as it is hepatically metabolized 3, 1, 2
Bivalirudin is contraindicated in severe renal failure 1
Danaparoid is not recommended as first-line in severe renal failure 3
For severe hepatic impairment (Child-Pugh C):
Bivalirudin, danaparoid, or fondaparinux may be used 1
Argatroban requires dose reduction and careful monitoring in hepatic impairment 4
For severe HIT (massive PE, extensive/arterial thrombosis, venous gangrene, consumption coagulopathy):
- Prefer argatroban or bivalirudin with strict biological monitoring due to their short half-lives and reversibility 3, 1
Specific Dosing from FDA Label:
Argatroban for HIT: 2 mcg/kg/min continuous infusion; obtain baseline aPTT before starting, then adjust dose to maintain aPTT 1.5-3 times baseline 4
Argatroban for PCI in HIT patients: 25 mcg/kg/min infusion plus 350 mcg/kg bolus over 3-5 minutes; check ACT 5-10 minutes after bolus (proceed if ACT >300 seconds) 4
Danaparoid: Must use therapeutic IV doses (NOT prophylactic doses), with monitoring of anti-Xa activity using specific calibration curve 3, 1
Laboratory Testing Strategy
Order anti-PF4 antibody testing (ELISA or chemiluminescent) for all intermediate or high probability cases—these have high sensitivity and negative predictive value but lower specificity 1
If anti-PF4 antibodies are positive with intermediate probability, perform a functional test (serotonin release assay or HIPA test) to confirm diagnosis 3, 1
If anti-PF4 antibodies are negative with intermediate probability, HIT is excluded and heparin can be resumed with close platelet monitoring 3
Never delay treatment while waiting for laboratory results if clinical probability is intermediate or high 3, 1
Transition to Oral Anticoagulation
Wait for platelet count recovery (>150,000/μL or return to baseline) before starting vitamin K antagonists 1, 2
Overlap parenteral anticoagulant with oral agent for at least 5 days when transitioning 1
Direct oral anticoagulants (DOACs) are acceptable alternatives to warfarin for long-term anticoagulation 3, 1
Perioperative Management
For patients with acute HIT (<1 month from diagnosis):
Postpone elective surgery beyond the first month if possible 1, 2
If surgery cannot be delayed, use short-acting agents: argatroban (stop 4 hours before procedure) or bivalirudin (stop 2 hours before procedure) 2
For cardiac surgery requiring cardiopulmonary bypass:
Systematically perform ELISA for anti-PF4 antibodies before surgery in patients with HIT history 1
Two acceptable strategies: (1) combination of IV antiplatelet agent with unfractionated heparin, or (2) use of thrombin inhibitor (bivalirudin or argatroban) 2
Common Pitfalls to Avoid
Do not use prophylactic doses of alternative anticoagulants—therapeutic doses are mandatory even without thrombosis 3, 1
Do not prescribe oral antiplatelet agents alone to treat acute HIT, as they are insufficient to prevent thrombosis 2
Do not insert inferior vena cava filters in acute HIT, as they may increase thrombotic risk 2
Do not use IV immunoglobulins as first-line treatment for acute HIT 2
Do not re-expose to heparin within 3 months of HIT diagnosis 1, 2
Long-Term Management
Document HIT diagnosis prominently in medical records with laboratory results 1
Provide patient with written documentation of HIT diagnosis and laboratory results 1
Schedule hematology follow-up within 3 months of diagnosis 1
For future anticoagulation needs, use oral anticoagulants (warfarin or DOACs) or fondaparinux—avoid all heparins 1, 2
Consider extended anticoagulation (3-6 months) depending on whether thrombosis occurred and other clinical factors 1, 2