Warfarin
Coumadin · Jantoven
Vitamin K antagonist oral anticoagulant
Inhibits vitamin K epoxide reductase (VKORC1) → depletes reduced vitamin K → ↓ synthesis of factors II, VII, IX, X and proteins C/S. Full effect takes days (waits for existing factor decay).
Indications
- •AF stroke prevention
- •Mechanical heart valves (only oral option)
- •VTE treatment/prevention
- •Antiphospholipid syndrome
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Maintenance | 2–10 mg PO daily, titrated to INR (goal 2–3, or 2.5–3.5 for mechanical mitral valve) | — |
| Reversal — urgent | 4-factor PCC (Kcentra) + IV vitamin K 5–10 mg; FFP if PCC unavailable | — |
Pharmacokinetics
Onset 24–72 h to therapeutic INR (factor VII falls first). Half-life ~40 h. Hepatic CYP2C9/VKORC1 — genetic + dietary + drug variability.
Side effects
- !Bleeding
- !Warfarin-induced skin necrosis (early, protein C deficiency)
- !Purple toe syndrome
- !Teratogen (fetal warfarin syndrome)
Contraindications
- ×Pregnancy
- ×Active bleeding
- ×Recent neuraxial/major surgery without INR normalization
Reversal / antidote
Vitamin K (slow, hours) + 4-factor PCC (Kcentra, immediate) for major bleed; FFP as alternative
Clinical pearls
- ★ASRA neuraxial: normalize INR to ≤1.5 (ideally normal) before neuraxial block or catheter removal.
- ★Bridging with heparin/LMWH for high-thrombotic-risk (mechanical mitral valve, recent VTE); many low-risk AF patients no longer bridged (BRIDGE trial).
- ★Only oral anticoagulant proven for mechanical valves — DOACs are contraindicated (RE-ALIGN trial harm).
Other drugs in Coagulation Related
- Heparin (unfractionated)
Activates antithrombin → inactivates IIa (thrombin) and Xa.
- Tranexamic Acid (TXA)
Reversibly binds plasminogen, blocking conversion to plasmin → preserves fibrin clot.
- Protamine Sulfate
Strongly basic (positive-charge) protein binds to highly acidic (negative-charge) heparin → inactive ionic complex → renal excretion. 1 mg protamine neutralizes ~100 units heparin.
- DDAVP (Desmopressin)
Selective V2 agonist (renal water retention + Factor VIII/vWF release from endothelial Weibel-Palade bodies). NO V1 vasopressor activity at therapeutic dose.
- Enoxaparin
Antithrombin-mediated inhibition, weighted toward factor Xa over IIa (~3.8:1). More predictable than UFH — no routine monitoring.
- Dalteparin
Antithrombin-mediated factor Xa > IIa inhibition. Similar profile to enoxaparin; preferred LMWH in cancer-associated VTE (CLOT trial).
- Tinzaparin
Antithrombin-mediated factor Xa > IIa inhibition; higher mean molecular weight than enoxaparin (anti-Xa:IIa ~1.9:1).
- Fondaparinux
Binds antithrombin → selective, exclusive factor Xa inhibition (no IIa activity). Does NOT cause HIT — safe alternative in HIT patients.
Browse all classes: /reference/drugs
Suggested reading
- •Miller's Anesthesia, 9e
- •FDA package insert
- •ASRA regional anesthesia in the anticoagulated patient guidelines, 2018
