What is the protocol for transitioning from heparin (unfractionated heparin) to warfarin (coumarin) therapy?

From the Guidelines

To transition from heparin to warfarin, start warfarin at a dose of 5mg daily while continuing heparin therapy, and maintain both medications until the INR reaches the therapeutic range (typically 2-3) for at least 2 consecutive days, as recommended by the American Heart Association/American College of Cardiology Foundation guide to warfarin therapy 1. When transitioning from heparin to warfarin, it is essential to overlap the two medications for at least 4-5 days to ensure continuous anticoagulation, as warfarin initially creates a paradoxical hypercoagulable state before its anticoagulant effect takes effect 1.

• The initial dose of warfarin can be 5mg daily, but lower doses (2-3mg) may be appropriate for elderly patients, those with liver disease, or patients at higher bleeding risk 1.
• Monitor INR daily during the transition period, and once the INR is therapeutic for at least 2 consecutive days, discontinue the heparin while continuing warfarin with regular INR monitoring to maintain the target range 1.
• For patients on low molecular weight heparin (LMWH) like enoxaparin, the same principles apply, but monitoring is simpler as LMWH doesn't require aPTT checks 1. The safety and effectiveness of warfarin therapy depend critically on maintaining the INR within the therapeutic range, and on-treatment analysis of primary prevention trials in atrial fibrillation found that a disproportionate number of thromboembolic and bleeding events occurred when the PT ratio was outside the therapeutic range 1.
• The INR should be checked daily until the therapeutic range has been reached and sustained for 2 consecutive days, then 2 or 3 times weekly for 1 to 2 weeks, then less often, according to the stability of the results 1.
• Some patients on long-term warfarin therapy experience unexpected fluctuations in dose-response due to changes in diet, concurrent medication changes, poor compliance, or alcohol consumption, and frequent monitoring is resumed when dose adjustments are required 1.

From the FDA Drug Label

CONVERSION FROM HEPARIN THERAPY Since the anticoagulant effect of warfarin sodium tablets is delayed, heparin is preferred initially for rapid anticoagulation Conversion to warfarin sodium tablets may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy and that warfarin sodium tablets therapy be overlapped with heparin for 4 to 5 days, until warfarin sodium tablets have produced the desired therapeutic response as determined by PT/INR When warfarin sodium tablets have produced the desired PT/INR or prothrombin activity, heparin may be discontinued. To ensure continuous anticoagulation when converting from Heparin Sodium Injection to warfarin, continue full heparin therapy for several days until the INR (prothromin time) has reached a stable therapeutic range. Heparin therapy may then be discontinued without tapering [see Drug Interactions (7.1)].

The transition from heparin to warfarin should be done by:

• Starting warfarin concomitantly with heparin therapy or delaying it by 3 to 6 days
• Overlapping warfarin with full-dose heparin therapy for 4 to 5 days
• Continuing heparin until warfarin has produced the desired therapeutic response as determined by PT/INR
• Discontinuing heparin when warfarin has reached a stable therapeutic range, without tapering 2 3 Key points:
• Continue full-dose heparin therapy during the transition
• Overlap warfarin with heparin for 4 to 5 days
• Monitor PT/INR to determine when to discontinue heparin

From the Research

Transitioning from Heparin to Warfarin

• The process of transitioning from heparin to warfarin involves careful planning and monitoring to ensure effective anticoagulation and minimize the risk of adverse events 4, 5, 6, 7, 8.
• When initiating warfarin therapy, the doses for patients aged <70 years is 4 mg, and for patients aged >70 years it is 3 mg 5.
• Heparin can be discontinued when the international normalized ratio (INR) is within the therapeutic range, which is typically between 2.0 and 3.0 4, 7.
• The INR should be monitored regularly to ensure that it remains within the therapeutic range, and warfarin doses should be adjusted as needed 4, 5, 7, 8.

Monitoring and Adjusting Warfarin Doses

• The activated partial thromboplastin time (APTT) and INR should be monitored regularly to assess the effectiveness of heparin and warfarin anticoagulation 7.
• Increasing proportions of time on heparin with an APTT ≥ 0.2 anti-X(a) U/mL and on warfarin with an INR ≥ 2.0 are associated with significant reductions in venous thromboembolism (VTE) recurrence 7.
• Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement are not independent predictors of recurrence 7.

Clinical Challenges and Potential Solutions

• The transition from heparin to warfarin can be associated with gaps in care related to anticoagulation therapy that increase the risk of adverse events, rehospitalizations, and death 8.
• Diligence, careful planning, and close communication between patients and healthcare providers during and after discharge are required to ensure that patients remain adequately and safely anticoagulated with warfarin in the outpatient setting 8.
• New oral anticoagulants may offer the possibility of safer and simpler care for patients requiring anticoagulation 8.