What is the recommended protocol for Coumadin (warfarin) therapy?

Warfarin (Coumadin) Therapy Protocol

For outpatients who are sufficiently healthy, initiate warfarin at 10 mg daily for the first 2 days, followed by INR-guided dosing; however, for elderly patients (≥65 years), those at increased bleeding risk, or those expected to have heightened sensitivity, start with 2-5 mg daily. 1, 2

Initial Dosing Strategy

Standard Outpatient Dosing

• Begin with 10 mg daily for 2 days in healthy outpatients, then adjust based on INR measurements 1
• This loading approach is recommended by the American College of Cardiology over starting with estimated maintenance doses 1

Modified Dosing for High-Risk Patients

• Use 2-5 mg daily for patients who are:
  • Elderly (≥65 years) 1, 2
  • At increased bleeding risk 1
  • Expected to have heightened warfarin sensitivity 1, 2
  • Debilitated 2

Concurrent Heparin Therapy

• When rapid anticoagulation is required, administer heparin concurrently with warfarin for at least 4 days until INR reaches therapeutic range for 2 consecutive days 1
• Heparin may be discontinued after INR has been therapeutic for at least two measurements taken more than 24 hours apart 3

Critical Pitfall: Loading doses larger than 10 mg increase hemorrhagic complications without providing faster protection against thrombus formation and should be avoided 2. The older European guideline recommendation of starting with 5 mg maintenance dosing 3 has been superseded by the American College of Cardiology's 10 mg loading protocol for healthy outpatients 1.

INR Monitoring Schedule

Initial Phase

• Check INR daily until therapeutic range is reached and sustained for 2 consecutive days 1, 2
• The anticoagulant effect typically occurs within 2-7 days, with therapeutic INR usually achieved in 5-7 days 3

Stabilization Phase

• Monitor INR 2-3 times weekly for 1-2 weeks after initial stabilization 3, 1
• Then weekly for 1 month 3

Maintenance Phase

• Gradually reduce monitoring frequency to intervals as long as 4 weeks for stable patients 3, 1
• Monthly monitoring thereafter if stability is maintained 3

Increased Monitoring Requirements

• More frequent monitoring is required during:
  • Changes in medications, particularly antibiotics 3
  • Changes in diet or dietary supplements 3
  • Intercurrent illness 3
  • Weight fluctuations 3
  • Any indication of minor bleeding or unexpected INR changes 3

Critical Pitfall: Elderly patients may require more frequent monitoring due to increased bleeding risk and greater INR fluctuations, particularly during illness or medication changes 3.

Target INR Ranges by Indication

Standard Intensity (INR 2.0-3.0)

• Atrial fibrillation 3, 2
• Venous thromboembolism 3
• Bioprosthetic valves (first 3 months in mitral or aortic position) 3, 2
• St. Jude Medical bileaflet valve in aortic position 2
• Valvular heart disease with atrial fibrillation or prior embolism 3

Higher Intensity (INR 2.5-3.5)

• Tilting disk valves and bileaflet mechanical valves in mitral position 2
• Caged ball or caged disk valves (plus aspirin 75-100 mg/day) 2
• Recurrent systemic embolism despite adequate anticoagulation (can increase to INR 2.5-3.5 or add aspirin 80-100 mg/day) 3

Post-Myocardial Infarction

• High-intensity warfarin (INR 3.0-4.0) without aspirin OR moderate-intensity warfarin (INR 2.0-3.0) with aspirin for up to 4 years in settings with meticulous INR monitoring 2
• For high-risk MI patients (large anterior MI, significant heart failure, intracardiac thrombus, history of thromboembolism): combined moderate-intensity warfarin (INR 2.0-3.0) plus low-dose aspirin (≤100 mg/day) for 3 months 2

Critical Pitfall: INR >4.0 provides no additional therapeutic benefit and significantly increases bleeding risk 3, 2. The bleeding risk increases exponentially with INR values above 3.0 3.

Management of Elevated INR

INR Above Therapeutic Range but <5.0 (No Bleeding)

• Reduce or omit the next dose and resume at lower dose when INR approaches desired range 3, 1

INR 5.0-9.0 (No Bleeding)

• For patients at low bleeding risk: Omit 1-2 doses and reinstate at lower dose when INR returns to therapeutic range 3, 1
• For patients at increased bleeding risk: Omit next dose AND give 1.0-2.5 mg oral vitamin K 3, 1
• If INR remains high at 24 hours, give additional 1.0-2.0 mg oral vitamin K 3

INR >9.0 (No Bleeding)

• Give 3-5 mg oral vitamin K 3, 1

Serious Bleeding (Any INR)

• Administer 5-10 mg IV vitamin K 1
• Give fresh frozen plasma or prothrombin complex concentrate for rapid reversal 3

Critical Pitfall: After high-dose vitamin K administration, warfarin resistance may occur, potentially requiring bridging with heparin until vitamin K effects subside 1. Intravenous vitamin K should be given slowly to avoid anaphylactoid reactions 3.

Management of Warfarin-Associated Bleeding

Active Bleeding with Hemoglobin Drop

• Stop warfarin immediately when significant bleeding occurs (e.g., 8 g/L hemoglobin drop in 24 hours) 1
• Initiate measures to control bleeding source urgently 1
• Do not give reversal agents unless bleeding progresses to major bleeding with hemodynamic instability 1
• Assess hemodynamic stability repeatedly while investigating bleeding source 1

Restarting Anticoagulation

• Delay restart if:
  • Bleeding source not identified 1
  • High risk of rebleeding 1
  • Bleeding occurred at critical site 1
• Once stable and bleeding controlled: Restart warfarin at lower dose than previously prescribed with continued INR monitoring 1

Critical Pitfall: Do not continue warfarin simply because hemoglobin drop doesn't meet strict major bleeding criteria—any significant unexplained hemoglobin drop represents a red flag for bleeding that could rapidly progress 1.

Perioperative Management

Preoperative Preparation

For patients at moderate-to-low thromboembolism risk:

• Stop warfarin 4-5 days before surgery to allow INR to return to normal (≤1.2) 3
• Alternative: Stop warfarin 2 days before surgery and give vitamin K 2.5 mg orally 2 days preoperatively 3
• Give prophylactic-dose heparin (5000 U subcutaneously every 12 hours) or LMWH (3000 U every 12 hours) preoperatively 3

For patients at high thromboembolism risk:

• Administer therapeutic-dose heparin (15,000 U subcutaneously every 12 hours) or LMWH (100 U/kg every 12 hours) after stopping warfarin 3
• Discontinue 24 hours before surgery 3
• For critical cases: Admit for continuous IV heparin (1300 U/h), stop 5 hours before surgery 3

Postoperative Management

• Restart heparin or LMWH in prophylactic doses 12 hours postoperatively along with warfarin 3
• Continue combination for 4-5 days until INR returns to desired range 3
• If high postoperative bleeding risk, delay heparin/LMWH for 24 hours or longer 3

Critical Pitfall: LMWH is not recommended for thromboprophylaxis in patients with prosthetic heart valves, as per FDA and manufacturer warnings 3.

Special Considerations

Pregnancy

• Replace oral anticoagulants with heparin during first trimester (risk of abortion and embryopathies) 3
• Replace with heparin during last 6 weeks before delivery (bleeding risks) 3
• Subcutaneous adjusted UFH or LMWH are long-term treatments of choice in pregnant women 3

Heparin-Induced Thrombocytopenia (HIT)

• Never use warfarin alone in acute HIT phase (can promote venous thrombosis progression, gangrene, or skin necrosis) 3
• Administer warfarin only under cover of effective parenteral anticoagulant (danaparoid sodium or argatroban) 3
• Start warfarin when platelet count >150 G/L 3
• Target INR 2.0-3.0 3

Skin Necrosis

• Most important non-hemorrhagic side effect, occurring during first week of treatment 3
• Associated with protein C and protein S deficiency 3