Mechanism of Action

Vitamin K antagonist: inhibits vitamin K epoxide reductase, so the liver cannot make functional clotting factors II, VII, IX, and X (plus proteins C and S). Because it blocks NEW factor production rather than destroying existing ones, full effect takes 3–5 days — factor VII falls first (raising PT/INR early), but true protection needs depletion of factor II (half-life ~60 h). This onset delay is why heparin must BRIDGE warfarin during initiation. Monitored by PT/INR (NOT aPTT — that's heparin).

3.5 (mech. mitral valve target top)

Sub-therapeutic

Therapeutic (most indications)

Supratherapeutic — bleeding risk

INR

Common Medications

warfarinPrototype

single high-yield agent; brand Coumadin

Indications

atrial fibrillation

stroke prevention; INR 2.0–3.0

venous thromboembolism

DVT/PE treatment; INR 2.0–3.0

mechanical heart valve

INR 2.0–3.0, or 2.5–3.5 for high-risk mechanical mitral valve

Side Effects

easy bruising

bleeding gums

nosebleeds

epistaxis

minor mucosal bleeding

Contraindications & Interactions

Contraindications

active bleeding

pregnancy

teratogen — fetal warfarin syndrome

Interactions

trimethoprim-sulfamethoxazole

inhibits CYP2C9 → warfarin level and INR rise

NSAIDs

ibuprofen adds antiplatelet effect → bleeding risk

antibiotics

many raise INR; notify provider before any new drug

herbal supplements

unpredictable INR shifts

abrupt change in vitamin K intake

leafy greens — keep CONSISTENT, do not eliminate

Administration & Monitoring

monitor PT/INR

NOT aPTT — aPTT is for heparin

INR 2.0–3.0 targetINR 2.0–3.0

most indications

INR 2.5–3.5 for high-risk mechanical mitral valveINR 2.5–3.5

frequent INR during titration

then routine intervals once stable

bridge with heparin at initiation

covers the 3–5 day onset delay

antidote: vitamin K (phytonadione)

reverses warfarin; full effect 6–8 h

4-factor PCC for life-threatening bleed

immediate factor replacement; give WITH IV vitamin K

Patient Teaching

keep consistent vitamin K intake

steady leafy greens — do NOT eliminate them

attend all INR appointments

take at the same time daily

use a soft toothbrush and electric razor

bleeding precautions

report unusual bruising or bleeding gums

go to the ED for black tarry stools

melena — major GI bleeding; also blood in urine

report new leg swelling

possible clot

avoid NSAIDs

use acetaminophen instead for pain

notify provider before any new drug or supplement

Report Nowescalate immediately

major hemorrhageBlack Box

FDA boxed warning — warfarin can cause fatal bleeding; hematemesis, GI bleed, intracranial bleed

melena

black tarry stools — GI bleeding; go to ED

hematuria

blood in urine

supratherapeutic INR with bleedingINR > 3.0

INR 5.8 / 9.2 in the published items — active bleed needs reversal

new unilateral leg swelling

possible DVT — clotting from SUB-therapeutic INR

Clinical Pearl

'2, 7, 9, 10 — takes time to win': warfarin blocks four vitamin-K factors and builds over days, so heparin must bridge it. Monitor PT/INR (not aPTT), keep vitamin K CONSISTENT not eliminated, and reverse with vitamin K — protamine is for heparin.