Doctors get bad grades in antithrombotics 101

In the July 11 issue of Archives of Internal Medicine is a survey from the National Anticoagulation Benchmark and Outcomes Report Steering Committee showing poor adherence to guidelines for antithrombotic therapies in a variety of clinical settings. Aspirin for myocardial infarction, warfarin for atrial fibrillation, treatment of venous thromboembolism (VTE) and prophylaxis for orthopedic procedures were evaluated.

Although practice patterns were found lacking in all areas one finding concerning treatment of VTE was particularly interesting. Almost half of patients with acute VTE had unfractionated or low molecular weight heparin discontinued too soon (before the INR was at least 2.0 for two consecutive days). As pointed out in the Archives article, the guidelines call for continuation of some form of heparin (unfractionated or low molecular weight) for at least four days AND until the INR is at least 2.0 for two consecutive days.

I suspect this failure of adherence is driven by pressure to discharge patients quickly and by a popular misconception that patients are adequately anticoagulated with warfarin as soon as the INR reaches 2.0. Such an approach is not only outside the guidelines but also pharmacologically irrational. The vitamin K dependent factors decay at different rates following the initiation of warfarin. Although factor VII, with the shortest half-life, is the major determinant of the INR the patient’s state of anticoagulation is determined by the other factors which have longer half lives. Put another way, when warfarin is initiated the initial rise in INR does not reflect anticoagulation of the patient. Worse yet, protein C, a vitamin K dependent anticoagulant has a short half-life similar to that of factor VII, thus rendering the patient hypercoagulable when the INR first rises. Here is a nice little review of the acute effects of warfarin from the Cleveland Clinic Journal of Medicine.