What dose of warfarin (Coumadin) do you start a patient on after initiating heparin and checking the International Normalized Ratio (INR)?

Initial Warfarin Dosing After Starting Heparin

For patients sufficiently healthy to be treated as outpatients, initiate warfarin therapy with 10 mg daily for the first 2 days followed by dosing based on INR measurements rather than starting with the estimated maintenance dose. 1

Recommended Initial Dosing Strategy

Outpatient Initiation

• For outpatients who are otherwise healthy, start with warfarin 10 mg daily for the first 2 days, then adjust based on INR measurements 1
• This approach results in shorter mean time to therapeutic INR (4.2 vs 5.6 days) compared to lower doses 1
• By day 5, approximately 86% of patients on 10 mg initial dosing will reach therapeutic range versus only 45% with 5 mg initial dosing 1

Inpatient or Higher-Risk Patient Initiation

• For elderly patients, inpatients, or those at increased risk of bleeding, start with 5 mg daily 1, 2
• Avoid higher loading doses in these populations as they can lead to excessive anticoagulation 2, 3
• Very elderly patients may require even lower initial doses (2-4 mg) 2

Timing of Warfarin Initiation with Heparin

• Begin warfarin on the first or second day of heparin therapy 1, 4
• Continue heparin and warfarin together for 4-5 days until warfarin has produced the desired therapeutic response 4
• Only discontinue heparin when the INR has been in the therapeutic range (2.0-3.0) for at least 2 consecutive days 1, 4

INR Monitoring Schedule

• Check INR daily until the therapeutic range has been reached and sustained for 2 consecutive days 1
• Then check 2-3 times weekly for 1-2 weeks 1
• Subsequently, reduce frequency according to stability of results 1
• When taking blood samples for INR while on heparin, draw samples at least:
  • 5 hours after the last IV bolus dose of heparin
  • 4 hours after cessation of continuous IV heparin infusion
  • 24 hours after the last subcutaneous heparin injection 4

Important Clinical Considerations

Factors Affecting Dosing Requirements

• Age: Older patients typically require lower doses 1, 2
• Sex: Female patients may require lower doses 5
• Comorbidities: Hepatic dysfunction affects warfarin metabolism 6
• Medications: Many drug interactions can affect warfarin response 1

Common Pitfalls to Avoid

• Excessive initial loading doses can lead to supratherapeutic INRs and increased bleeding risk 3
• In one study, 36% of patients receiving 10 mg loading doses had INRs >3.0 at 60 hours compared to 0% in the 5 mg group 3
• Failure to continue heparin until warfarin has reached therapeutic effect can increase thrombotic risk 4
• Inadequate monitoring during the initial phase can miss dangerous INR elevations 1

Safety Considerations

• A 10 mg loading dose causes more rapid decreases in protein C levels than factor II or X, which theoretically could create a transient hypercoagulable state 1, 3
• However, this risk is mitigated by concurrent heparin therapy during warfarin initiation 1
• The risk of bleeding with appropriate monitoring during initiation is low, with studies showing major bleeding rates of approximately 1% 7

By following these evidence-based recommendations for warfarin initiation after starting heparin, you can optimize the balance between achieving therapeutic anticoagulation efficiently while minimizing bleeding risks.