Why we use it
Warfarin predates the DOACs but hasn’t been retired. It remains first-line for mechanical heart valves and significant mitral stenosis, where DOACs are contraindicated (RE-ALIGN showed harm with dabigatran in mechanical valves). It is also used when DOACs aren’t appropriate — severe renal impairment, certain antiphospholipid syndromes, cost, or adherence patterns favoring monitored therapy.
Mechanism
Warfarin blocks vitamin K epoxide reductase, depleting the reduced vitamin K needed to carboxylate factors II, VII, IX, and X (and the anticoagulant proteins C and S). Because circulating factors must decay, the anticoagulant effect lags days behind the dose despite an early rise in INR — the INR moves first with factor VII (short half-life), but true antithrombotic effect depends on factor II.
Dosing and monitoring
- Individualized; most indications target INR 2–3, mechanical mitral valves 2.5–3.5
- Monitor INR frequently at initiation, then space out once stable
- Diet (vitamin K intake), alcohol, illness, and countless drugs shift the INR — counsel consistency
Periprocedural management in EP
- Device implants (pacemaker/ICD) and AF ablation are frequently performed on uninterrupted therapeutic warfarin. BRUISE CONTROL showed continued warfarin caused far fewer pocket hematomas than heparin bridging.
- Bridging with heparin/LMWH is reserved for the highest thrombotic risk (e.g., some mechanical valves) — and it increases bleeding.
- Confirm the INR is in range the morning of the procedure.
Interactions worth knowing
- Amiodarone — potentiates warfarin; preemptively cut the dose 30–50% and recheck INR
- Antibiotics (metronidazole, TMP-SMX, fluconazole, macrolides) — raise INR
- Many anticonvulsants and rifampin — induce metabolism, lower INR
- NSAIDs/antiplatelets — additive bleeding without changing INR
Reversal
- Major/life-threatening bleeding: 4-factor PCC plus IV vitamin K (PCC works in minutes; vitamin K sustains the reversal). FFP only if PCC unavailable.
- High INR, no significant bleeding: hold ± oral vitamin K, dose by INR and bleeding risk.
- Remember vitamin K’s effect takes hours — PCC is what buys time in an emergency.
Common pitfalls
- Forgetting to down-titrate warfarin when starting amiodarone.
- Bridging a low-thrombotic-risk patient and causing a pocket hematoma.
- Assuming a therapeutic INR equals full antithrombotic effect on day 2 — factor II hasn’t fallen yet.
- Using warfarin reversal logic for DOAC bleeding (different agents — idarucizumab, andexanet).