What is the appropriate use and management of Warfarin (anticoagulant) in patients requiring anticoagulation?

Warfarin Management

Warfarin remains the anticoagulant of choice for mechanical heart valves, left ventricular thrombus, and left ventricular assist devices, with a target INR of 2.0-3.0 for most indications and 2.5-3.5 for mechanical mitral valves. 1, 2

Primary Indications and Target INR

Mechanical Heart Valves

• Bileaflet aortic valve (e.g., St. Jude Medical): Target INR 2.5 (range 2.0-3.0) 2
• Tilting disk or bileaflet mitral valve: Target INR 3.0 (range 2.5-3.5) 2
• Caged ball or caged disk valves: Target INR 3.0 (range 2.5-3.5) plus aspirin 75-100 mg daily 2
• Warfarin is currently the only FDA-approved anticoagulant for mechanical valves; DOACs are contraindicated 1, 3

Atrial Fibrillation

• High-risk nonvalvular AF (prior stroke/TIA, age >75, heart failure, hypertension, diabetes): Target INR 2.0-3.0 2
• Valvular AF (moderate-severe mitral stenosis or mechanical valve): Target INR 2.0-3.0 2
• Patients with CHA₂DS₂-VASc ≥4 have particularly high thrombotic risk requiring anticoagulation 1

Venous Thromboembolism

• Provoked DVT/PE: 3 months of therapy, target INR 2.0-3.0 2
• Unprovoked DVT/PE: 6-12 months minimum, consider indefinite therapy 2
• Recurrent VTE or thrombophilia: 12 months to indefinite, target INR 2.0-3.0 2
• Active cancer with VTE: Warfarin is acceptable when LMWH unavailable, target INR 2.0-3.0 1

Post-Myocardial Infarction

• High-risk MI (large anterior MI, heart failure, LV thrombus, prior embolism): Combined moderate-intensity warfarin (INR 2.0-3.0) plus low-dose aspirin ≤100 mg daily for 3 months 2
• Most moderate/low-risk MI patients should receive aspirin alone rather than warfarin 2

Initiation and Dosing

Starting Warfarin

• Initial dose: 2-5 mg daily; avoid loading doses as they increase bleeding risk without faster therapeutic effect 2
• Elderly patients (≥75 years): Start at lower end of range (2 mg daily) as they require approximately 1 mg/day less than younger patients 1
• Concurrent heparin or LMWH should be administered for 4-5 days until INR therapeutic for ≥2 consecutive measurements >24 hours apart 1, 2

Monitoring Schedule

• Initial phase: Daily INR until stable (typically 5-7 days) 1
• Weeks 1-2: INR 2-3 times weekly 1
• Weeks 3-4: Weekly INR 1
• Maintenance: Monthly INR if stable; more frequent if medication changes, illness, or dietary changes 1

Managing Out-of-Range INR

Supratherapeutic INR Without Bleeding

• INR 3.0-5.0: Withhold one dose or reduce dose; resume when INR therapeutic 1
• INR 5.0-9.0, low bleeding risk: Withhold warfarin, monitor closely 1
• INR 5.0-9.0, high bleeding risk: Omit dose and give vitamin K 1.0-2.5 mg orally 1
• INR >9.0: Give vitamin K 2.0-4.0 mg orally; repeat 1.0-2.0 mg if INR remains high at 24 hours 1

Active Bleeding

• Emergency reversal: Prothrombin complex concentrate (PCC) 50 IU/kg is preferred over fresh frozen plasma 1, 4
• Vitamin K 10 mg IV: Administer concurrently, but note this may preclude re-warfarinization for several days 1
• Avoid high-dose vitamin K (>10 mg) routinely as it creates warfarin resistance lasting up to one week 4

Subtherapeutic INR

• Increase weekly warfarin dose by 5-20% and recheck INR within 3-7 days 3
• Investigate non-adherence, drug interactions, dietary vitamin K intake, or malabsorption 1, 5

Perioperative Management

Low Thrombotic Risk

• Stop warfarin 4-5 days preoperatively to allow INR to normalize (≤1.2) 1
• Alternative: Give vitamin K 2.5 mg orally 2 days before procedure to shorten off-warfarin period 1
• Resume warfarin postoperatively when hemostasis achieved 1

High Thrombotic Risk (Mechanical Valves, Recent VTE <3 months, Prior Thromboembolism)

• Bridging anticoagulation required: 1
  • Stop warfarin 4-5 days preoperatively
  • Start therapeutic-dose LMWH or unfractionated heparin when INR <2.0
  • Stop LMWH 24 hours preoperatively or UFH 4-6 hours preoperatively
  • Resume heparin/LMWH 12-24 hours postoperatively (longer if high bleeding risk)
  • Restart warfarin concurrently; continue bridging until INR therapeutic ≥2 consecutive days

Moderate Thrombotic Risk

• Prophylactic-dose bridging: UFH 5000 units SC q12h or LMWH 3000 units SC q12h 1
• Resume 12 hours postoperatively along with warfarin 1

Bleeding Risk Factors

Patient-Specific Risk Factors

• Age ≥65 years: Significantly increased bleeding risk, especially with INR >6.0 1, 3
• Prior stroke or GI bleeding: Additive risk factors 1
• Comorbidities: Renal insufficiency, anemia, liver disease, hypoalbuminemia 1
• Concomitant antiplatelet therapy: Aspirin, NSAIDs, or clopidogrel substantially increase bleeding risk 1

Risk Stratification

• Patients with 2-3 risk factors have much higher bleeding incidence than those with 0-1 1
• Bleeding at INR ≤3.0 frequently indicates underlying GI or GU lesion requiring investigation 1

Special Populations

Nephrotic Syndrome

• Full anticoagulation indicated for thromboembolic events 1
• Prophylactic anticoagulation when albumin <20-25 g/L plus proteinuria >10 g/day, BMI >35, heart failure, or immobilization 1
• Warfarin preferred over DOACs due to lack of pharmacokinetic data in hypoalbuminemia 1
• Monitor INR frequently as warfarin-protein binding fluctuates with changing albumin 1

Patients with Prior Bleeding on Warfarin

• If bleeding occurred with supratherapeutic INR, resume warfarin once bleeding stopped and cause corrected 1
• Mechanical valves with persistent bleeding risk: Reduce target to INR 2.0-2.5 1
• Atrial fibrillation with persistent bleeding risk: Reduce target to INR 1.5-2.0 (efficacy diminished but not abolished) 1

Restarting Anticoagulation After Bleeding

High Thrombotic Risk

• Parenteral anticoagulation can be restarted within 1-3 days with close monitoring in most patients 1
• Unfractionated heparin IV preferred for high rebleeding risk due to short half-life and reversibility with protamine 1
• Prophylactic-dose heparin (UFH or LMWH SC) may reduce rebleeding risk more than therapeutic doses 1

Contraindication to Anticoagulation

• Left atrial appendage closure for AF patients (endocardial devices require 45 days therapeutic anticoagulation; epicardial devices do not) 1
• Retrievable IVC filters for acute proximal DVT, though use judiciously as trials show increased DVT risk without mortality benefit 1

Common Pitfalls

• Assuming adequate anticoagulation protects against thrombosis: Subtherapeutic INR or warfarin resistance can still allow DVT/PE 4, 5
• Using fresh frozen plasma for urgent reversal: PCC is superior for rapid INR correction 1, 4
• Routine bridging for atrial fibrillation: Not recommended for most AF patients undergoing surgery 1
• Fixed-dose warfarin regimens: Unlikely to maintain patients in therapeutic range; dose adjustments required even during maintenance 6
• Ignoring drug-drug interactions: Antibiotics, NSAIDs, and numerous other medications significantly affect warfarin metabolism 1, 5