Anticoagulants — warfarin, heparin, LMWH, DOACs

◆Mechanism & monitoring

• •Unfractionated heparin (UFH): activates antithrombin → inhibits IIa + Xa; monitor aPTT (or anti-Xa); reversed by protamine
• •Low molecular weight heparin (LMWH, enoxaparin): inhibits Xa >> IIa; monitor anti-Xa (only in renal failure, pregnancy, extremes of weight); partial reversal with protamine
• •Warfarin: inhibits vitamin K epoxide reductase → ↓ factors II, VII, IX, X (and proteins C, S); monitor INR (target 2–3, or 2.5–3.5 for mechanical mitral valve)
• •DOACs: apixaban, rivaroxaban, edoxaban (anti-Xa); dabigatran (anti-IIa); no routine monitoring; renal clearance matters

◆Reversal agents

• •Warfarin: vitamin K (PO/IV) + 4-factor PCC (immediate) or FFP (slower)
• •Heparin: protamine sulfate (1 mg per 100 units UFH)
• •Dabigatran: idarucizumab
• •Apixaban / rivaroxaban: andexanet alfa (or 4-factor PCC if not available)

◆When to pick which

• •Acute DVT/PE, hemodynamically stable: DOAC (apixaban or rivaroxaban) → continue ≥3 mo (longer if unprovoked)
• •Pregnancy: LMWH (preferred); NEVER warfarin (teratogen) or DOACs (no data, placenta-crossing)
• •Mechanical heart valve: WARFARIN only (DOACs failed RE-ALIGN trial)
• •Severe renal failure (CrCl <15–30): warfarin or UFH; DOACs/LMWH require dose adjustment or avoidance
• •Active cancer-associated VTE: DOAC (apixaban) or LMWH
• •AFib + valvular (moderate–severe MS): WARFARIN; DOACs in non-valvular only

◆Heparin-induced thrombocytopenia (HIT)

• •Suspect: platelet drop >50% from baseline OR <100,000 between days 5–14 of heparin (sooner if prior exposure)
• •Paradoxical thrombosis (arterial or venous) despite low platelets
• •Stop ALL heparin (including LMWH and flushes); start argatroban or fondaparinux (no platelet effect)
• •Do NOT give warfarin until platelets recover and on alternative anticoag (risk of skin necrosis)
• •4Ts score for pretest probability; confirm with anti-PF4 ELISA → serotonin release assay if equivocal

◆Other key warnings

• •Warfarin skin necrosis: paradoxical clotting in first 5 days (protein C deficiency unmasked) — bridge with heparin
• •Warfarin teratogen: fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses), CNS abnormalities
• •Long-term warfarin: hair loss, purple toe syndrome (cholesterol embolization), osteoporosis
• •DOACs: do not crush enteric-coated formulations; check for drug interactions (CYP3A4 inducers ↓ levels)

Anticoagulant comparison