What are the guidelines for initiating and managing Coumadin (warfarin) therapy in patients requiring anticoagulation?

Warfarin (Coumadin) Initiation and Management

Start warfarin at 2-5 mg daily (not loading doses) with lower doses (2 mg) for elderly, debilitated patients, or those with CYP2C9/VKORC1 genetic variants, and adjust based on INR monitoring to achieve target range of 2.0-3.0 for most indications. 1

Initial Dosing Strategy

• Begin with 2-5 mg daily, with the lower end (2 mg) preferred for patients over 65 years, debilitated patients, or those with genetic variants affecting warfarin metabolism 1
• Avoid loading doses entirely - they increase hemorrhagic complications without providing faster protection against thrombosis 1, 2
• Start heparin or LMWH concurrently and continue for 4-5 days until INR stabilizes in therapeutic range, as warfarin's anticoagulant effect (particularly factor II suppression) is delayed 2

Critical pitfall: Loading doses of warfarin are contraindicated despite historical practice - they do not accelerate therapeutic anticoagulation and significantly increase bleeding risk 1.

Target INR Ranges by Indication

Standard Intensity (INR 2.0-3.0)

• Venous thromboembolism (DVT/PE): First episode secondary to transient risk factor (3 months), idiopathic (6-12 months), or indefinite for recurrent episodes 1
• Atrial fibrillation (non-valvular): All high-risk patients (age >75, prior stroke/TIA, heart failure, hypertension, diabetes) 1
• Bileaflet mechanical aortic valve (St. Jude Medical type) 1
• Post-myocardial infarction: Moderate-intensity with aspirin ≤100 mg/day 1

Higher Intensity (INR 2.5-3.5)

• Mechanical mitral valve or combined mitral/aortic valves 1
• Tilting disk valves and bileaflet mechanical valves in mitral position 1
• Caged ball or caged disk valves (combined with aspirin 75-100 mg/day) 1

Important distinction: INR >4.0 provides no additional therapeutic benefit and significantly increases bleeding risk 1.

INR Monitoring Protocol

• Daily INR checks after initial dose until results stabilize in therapeutic range 1
• Twice to three times weekly during the first 2 weeks after stabilization 3
• Weekly intervals once stable, then extend to every 4 weeks maximum for well-controlled patients 3, 1
• Additional testing required when switching warfarin products, starting/stopping interacting medications, or with irregular medication adherence 1

Dose Adjustment for Subtherapeutic INR

• For INR 1.4 (subtherapeutic): Increase weekly warfarin dose by 5-20% and recheck INR within 3-7 days 4
• Never administer vitamin K for low INR - vitamin K is only indicated for elevated INR with or without bleeding 4
• Consider bridging with LMWH only for very high-risk patients (mechanical mitral valve, recent thromboembolism within 3 months, or history of thromboembolism while anticoagulated) 4

Management of Elevated INR

INR 4.5-10.0 Without Bleeding

• Withhold warfarin with careful monitoring if no bleeding and no high bleeding risk 5
• Administer oral vitamin K₁ 1-2.5 mg for INR 5.0-9.0 without bleeding 6
• Give vitamin K₁ 3-5 mg orally for INR >9.0 6
• Recheck INR within 24 hours after vitamin K administration 6

Major Bleeding with Elevated INR

• IV vitamin K₁ 10 mg by slow infusion plus prothrombin complex concentrate (PCC) or fresh frozen plasma 6, 5, 7
• PCC preferred over FFP for immediate reversal - Prothrombinex-VF is the standard PCC in Australia/New Zealand 5
• Vitamin K₁ essential for sustaining reversal achieved by PCC or FFP 5

Critical warning: Avoid high-dose vitamin K (10 mg) for non-bleeding situations as it causes warfarin resistance for up to one week if warfarin needs restarting 6.

Perioperative Management

Low Thromboembolism Risk (e.g., atrial fibrillation alone)

• Stop warfarin 4-5 days preoperatively to allow INR return to ≤1.5 3, 5
• Resume maintenance dose postoperatively with low-dose heparin (5000 U subcutaneously every 12 hours) if needed 3

Moderate Risk

• Stop warfarin 4-5 days before surgery 3
• Give prophylactic heparin 5000 U (or LMWH 3000 U) subcutaneously every 12 hours preoperatively 3
• Restart heparin/LMWH 12 hours postoperatively along with warfarin until INR therapeutic 3

High Risk (mechanical mitral valve, recent VTE, prior stroke)

• Therapeutic-dose LMWH 100 U/kg subcutaneously every 12 hours or heparin 15,000 U every 12 hours, discontinued 24 hours before surgery 3
• Alternative: Admit for IV heparin 1300 U/hour, stopped 5 hours before surgery 3
• Restart prophylactic doses 12 hours postoperatively with warfarin 3

Surgery can proceed safely with INR ≤1.5 - for minor procedures with low bleeding risk, warfarin may not require interruption 5.

Special Populations

Pregnancy

• Warfarin is contraindicated - it crosses the placenta causing embryopathy in first trimester and CNS abnormalities/fetal bleeding later 3
• Use therapeutic LMWH or adjusted-dose UFH throughout pregnancy 3
• Switch to heparin during first trimester and last 6 weeks before delivery 3

Postoperative Atrial Fibrillation After Cardiac Surgery

• If AF persists >48 hours: Start warfarin targeting INR 2.0-3.0 without heparin bridging due to bleeding risk 3
• May start warfarin without heparin given enhanced bleeding tendency post-cardiac surgery 3
• Stop anticoagulation if sinus rhythm returns, though consider continuing 1 month post-conversion due to persistent atrial dysfunction 3
• Reduce warfarin dose 25-40% if concurrent amiodarone therapy 3

Warfarin Hypersensitivity Pattern

• Persistent INR elevation for 8+ days after final dose indicates hypersensitivity requiring permanent discontinuation or extreme dose reduction 6
• Consider DOACs (dabigatran, rivaroxaban, apixaban) as alternatives for patients unable to maintain therapeutic INR 6
• If warfarin required despite hypersensitivity: Target lower INR 2.0-2.5 with daily monitoring for 2 weeks after dose changes, consider genetic testing 6

Maintenance Therapy

• Most patients maintained on 2-10 mg daily with dose adjustments based on INR response 1
• Suspect warfarin resistance if large daily doses required to maintain therapeutic INR 1
• Screen for drug interactions - antibiotics, NSAIDs, aspirin dramatically increase bleeding risk 6
• Counsel on consistent dietary vitamin K intake to avoid INR destabilization 6, 4

Missed Dose Management

• Take missed dose same day when remembered - do not double the next dose 1
• Contact physician for guidance rather than self-adjusting 1

Key advantage of anticoagulation clinics: Time in therapeutic range increases from 33-64% in usual care to 56-93% with specialized management, with fewer bleeding events 1.