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Varfarina (Coumadin): Mecanismo de Anticoagulação, História e Monitoramento

Warfarin is a vitamin K antagonist (VKA) used for thromboembolism prevention/treatment.

Mechanism

Inhibits vitamin K epoxide reductase (VKORC1) → blocks γ-carboxylation of Factors II, VII, IX, X, proteins C/S → ↓ functional clotting factors.

History

• 1940s: Karl Link (UW-Madison) identified dicoumarol in moldy sweet clover causing cattle hemorrhage.
• 1948: Warfarin developed as rodenticide.
• 1954: Approved for human use after Eisenhower's MI.
• Not from snake venom; diphacinone is a separate rodenticide.

Indications

• Atrial fibrillation (CHA₂DS₂-VASc ≥2)
• Mechanical heart valves
• VTE treatment/prevention (DVT/PE)
• Antiphospholipid syndrome

Monitoring

INR target 2.0–3.0 (most); 2.5–3.5 (mechanical mitral). Frequent initially; stable q4wk. Diet (vitamin K consistency), drug interactions (antibiotics, amiodarone, NSAIDs), genetics (CYP2C9, VKORC1) affect dose.

Reversal

Vitamin K (oral/IV), 4-factor PCC (urgent), andexanet alfa (factor Xa inhibitors — not warfarin).

DOACs now preferred for most non-valvular AF/VTE; warfarin remains for mechanical valves, APS, severe renal impairment.