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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- HIT is thrombocytopenia with paradoxical high thrombosis risk, not a bleeding disorder
- Typical onset is 5-10 days after heparin; rapid onset occurs with heparin exposure in the past 30-100 days
- Use the 4Ts score before testing: thrombocytopenia, timing, thrombosis, other causes
- Stop all heparin immediately and start a non-heparin anticoagulant when intermediate/high probability
- Warfarin is contraindicated acutely until platelets recover because it can cause venous limb gangrene
Overview
HIT type II is an immune reaction in which IgG antibodies form against platelet factor 4-heparin complexes. Fc receptor activation causes platelet activation, thrombocytopenia, and intense thrombin generation. Thrombosis may be venous or arterial and can be catastrophic. The relative platelet fall matters even if the absolute count remains above 150,000/µL.
Epidemiology
HIT occurs most often in hospitalized surgical and cardiac surgery patients receiving unfractionated heparin. Risk is lower with LMWH and rare with fondaparinux. It can occur after heparin flushes, dialysis circuits, or heparin-coated catheters.
Clinical Features
Symptoms
New DVT, PE, limb ischemia, stroke, or MI after heparin exposure
Skin necrosis at heparin injection sites
Acute systemic reaction after IV heparin bolus: fever, chills, hypertension, dyspnea
Bleeding is uncommon despite thrombocytopenia
Signs
Platelet fall >50% from baseline
Thrombosis, livedo, skin necrosis, or digital ischemia
Adrenal hemorrhage with shock can occur from adrenal vein thrombosis
Investigations
First-line
4Ts scoreLow score makes HIT unlikely and avoids false-positive PF4 testing
CBC trendPlatelet fall usually day 5-10 or rapid if recent exposure
Evaluate for thrombosisDoppler ultrasound or CT pulmonary angiography when symptoms suggest VTE/PE
Second-line
PF4-heparin ELISASensitive but not specific; positive result requires clinical context and often functional confirmation
Serotonin release assayFunctional assay with high specificity; confirms HIT when available
Baseline coagulation and renal/liver functionGuides choice of non-heparin anticoagulant
Specialist
Hematology consultationRecommended for intermediate/high probability HIT, thrombosis, cardiac surgery complexity, or need for procedures
1
Immediate action
- Stop all heparin products, including flushes and heparin-coated catheters when feasible
- Start non-heparin anticoagulation for intermediate/high 4Ts score while testing is pending
- Do not wait for confirmatory testing when probability is significant
2
Non-heparin anticoagulants
- Argatroban: useful in renal failure; monitor aPTT; avoid or dose reduce in liver dysfunction
- Bivalirudin: useful in procedures or critical illness; short half-life
- Fondaparinux or a DOAC may be used in stable selected patients
- Avoid platelet transfusion unless life-threatening bleeding
3
Transition and duration
- Do not start warfarin until platelets recover to at least 150,000/µL
- If warfarin was started, stop it and give vitamin K
- Treat isolated HIT for about 4 weeks; HIT with thrombosis generally requires about 3 months of anticoagulation
Complications
- Venous thrombosis: DVT and PE are common
- Arterial thrombosis: Limb ischemia, stroke, MI
- Venous limb gangrene: Warfarin started too early causes protein C depletion in active HIT
- Adrenal hemorrhage: From adrenal vein thrombosis
USMLE Step 2 CK Exam Tips
- 1Platelets fall 5-10 days after heparin + new clot = HIT
- 2HIT is prothrombotic; do not be reassured by thrombocytopenia
- 3Use 4Ts score first; low probability means do not test or treat for HIT
- 4Stop heparin and start argatroban/bivalirudin/fondaparinux — do not just stop heparin
- 5Do not start warfarin in acute HIT until platelet recovery
- 6PF4 ELISA is sensitive; serotonin release assay is confirmatory
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