What are the steps to diagnose and manage Heparin-Induced Thrombocytopenia (HIT)?

Diagnosing Heparin-Induced Thrombocytopenia (HIT)

Initial Clinical Assessment

When HIT is suspected, immediately calculate the 4T score to determine pre-test probability, and if the score is intermediate (4-5) or high (≥6), stop all heparin immediately and start therapeutic-dose alternative anticoagulation without waiting for laboratory confirmation. 1, 2

The 4T Score Components

The 4T score stratifies patients into three risk categories based on four clinical criteria 1, 2:

• Low probability (≤3 points): HIT can be excluded, continue heparin with close platelet monitoring 1, 2
• Intermediate probability (4-5 points): Stop all heparin, initiate therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing 1, 2
• High probability (≥6 points): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing—do not wait for results before treating 1, 2

Special Consideration for Post-Cardiac Surgery Patients

In post-cardiac surgery patients, a "biphasic" pattern in platelet count evolution strongly suggests HIT, and the 4T score is less reliable in this population 1. Look specifically for an initial platelet drop followed by recovery, then a second drop occurring 4-14 days after heparin exposure 1.

Laboratory Testing Strategy

First-Line Immunoassay Testing

For intermediate or high pre-test probability, immediately perform anti-PF4 antibody testing (ELISA or chemiluminescent immunoassay) while simultaneously initiating alternative anticoagulation. 1, 2

• These immunological tests have high sensitivity and negative predictive value but lower specificity 1
• A negative anti-PF4 antibody test in patients with intermediate probability excludes HIT, and heparin can be resumed with close platelet monitoring 1

Confirmatory Functional Testing

If anti-PF4 antibodies are positive with intermediate probability, perform a functional test (serotonin release assay [SRA] or heparin-induced platelet aggregation [HIPA] test) to confirm the diagnosis 1, 3, 4. These functional assays detect only clinically relevant platelet-activating antibodies and are superior to immunoassays in discerning which antibodies cause actual HIT 4.

Immediate Management Actions

Heparin Discontinuation

Stop all forms of heparin exposure immediately, including 1, 2:

• Intravenous unfractionated heparin
• Subcutaneous low molecular weight heparin (LMWH cross-reacts with HIT antibodies in 80-90% of cases) 1
• Heparin flushes for IV lines
• Heparin-coated catheters 1, 2

Alternative Anticoagulation Initiation

Start therapeutic-dose non-heparin anticoagulation immediately, even if thrombosis is not present, because untreated HIT carries a 30-50% risk of developing thrombosis. 1, 2

Do not use prophylactic doses—therapeutic anticoagulation is mandatory because HIT creates a prothrombotic state with markedly increased thrombin generation that persists even after heparin discontinuation 1.

Alternative Anticoagulant Selection Algorithm

For Patients with Normal Renal and Hepatic Function

Argatroban is the preferred first-line agent, starting at 2 mcg/kg/min as continuous IV infusion, with aPTT monitoring to maintain 1.5-3 times baseline value. 1, 2, 5

Check aPTT 2 hours after starting infusion and after any dose adjustment 1.

For Patients with Severe Renal Impairment (CrCl <30 mL/min)

Argatroban is the only recommended agent because it undergoes hepatic metabolism rather than renal clearance. 1, 2

For Patients with Severe Hepatic Impairment

Reduce argatroban starting dose to 0.5 mcg/kg/min if the patient has moderate or severe hepatic impairment, heart failure, multiple organ dysfunction, or is post-cardiac surgery 6, 1. Alternatively, consider bivalirudin, danaparoid, or fondaparinux 1, 2.

For Severe HIT with Life-Threatening Thrombosis

Prefer argatroban or bivalirudin with strict biological monitoring due to their short half-lives (allowing rapid titration and reversal) and demonstrated reduction in new thrombosis (RR 0.29) compared to discontinuing heparin alone 1, 2.

For Stable Patients Without Severe Organ Dysfunction

Fondaparinux is an acceptable option that does not require specific monitoring and has demonstrated similar effectiveness and safety as argatroban and danaparoid in propensity-matched studies 2, 7. Prophylactic fondaparinux doses appear effective if no indication for full anticoagulation exists 7.

Emerging Option: Direct Oral Anticoagulants (DOACs)

Rivaroxaban may be used in non-severe cases (without life-threatening or limb-threatening thrombosis) at 15 mg twice daily until platelet recovery or day 21, then 20 mg daily for at least one month. 6

However, DOACs should not be used as first-line therapy in severe HIT, and their prescription should not lead to neglecting confirmatory biological testing 6.

Monitoring and Duration of Therapy

Continue alternative anticoagulation until platelet count recovers to at least 150,000/μL or returns to baseline 1, 2. The minimum duration is 1:

• 4 weeks for isolated HIT (without thrombosis)
• 3 months for HIT with thrombosis (HITTS)

Monitor daily complete blood counts to track platelet recovery 1.

Transition to Oral Anticoagulation

Wait for platelet count recovery (>150,000/μL) before transitioning to vitamin K antagonists (VKAs) because VKAs can cause venous limb gangrene in acute HIT. 1, 2

When transitioning 1, 2:

• Overlap parenteral anticoagulant with warfarin for at least 5 days
• Use warfarin (coumadin) rather than other VKAs 6
• For argatroban-to-warfarin transition, measure INR after stopping argatroban to confirm therapeutic range due to argatroban's effect on INR 6

Direct oral anticoagulants (VKA or DOAC) are acceptable alternatives to warfarin for long-term anticoagulation 1.

Critical Pitfalls to Avoid

• Never delay stopping heparin while waiting for laboratory results if clinical suspicion is intermediate or high—the thrombotic risk is immediate and severe 1, 2
• Never give platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombosis in HIT 1, 2
• Never use prophylactic doses of alternative anticoagulants—therapeutic doses are required even without thrombosis 1, 2
• Never start VKAs in the acute phase before platelet recovery, as they can promote venous thrombosis progression and gangrene 6, 1, 2
• Never insert inferior vena cava filters in the acute phase of HIT, as this does not improve outcomes 1
• Never use oral antiplatelet agents alone to treat acute HIT, as they do not effectively prevent thrombosis 2

Long-Term Management and Documentation

• Document HIT diagnosis prominently in medical records with laboratory results 1
• Provide patients with documentation of their diagnosis 1
• Schedule follow-up with hematology within 3 months of diagnosis 1
• Avoid re-exposure to heparin, especially within 3 months of HIT diagnosis 1, 2
• For future anticoagulation needs, use oral anticoagulants (VKA or DOAC) or fondaparinux 1, 2

Perioperative Considerations

For patients with acute HIT requiring surgery 1, 2:

• Postpone elective surgery beyond the first month if possible to minimize thrombotic complications
• If surgery cannot be delayed, use short-acting agents like argatroban (stop 4 hours before procedure) or bivalirudin (stop 2 hours before procedure)
• For cardiac surgery in patients with history of HIT, systematically perform ELISA for anti-PF4 antibodies before surgery 1