Duration of Therapy
The duration of anticoagulant therapy must be tailored to the individual patient. Patients with slowly resolving risk factors, eg, prolonged immobilization, should be treated for at least three months; patients with tumors, antithrombin III or protein C deficiency, or recurrent venous thromboembolism should be treated indefinitely. In the only controlled trial that addressed this issue, two weeks of adequate anticoagulation was not sufficient. In many patients whose risk factors can be interrupted, eg, estrogen use or transient immobilization, a sufficient length of treatment may be shorter than three months. A clinical trial testing a shorter length of anticoagulation against three months is needed in patients without continuing risk factors.
The major complication associated with coumarin use is hemorrhage. Incidence of bleeding is crudely related to prolongation of the prothrombin time, but bleeding also occurs in patients with prothrombin times prolonged 1.5-2 times the baseline value with rabbit brain thromboplastin. In an effort to minimize bleeding, individuals have sought to find the lowest effective level of anticoagulation, and current evidence strongly suggests that many patients are being slightly overtreated. Any vascular site in the body can bleed with coumarin therapy, but many observers have been impressed with the frequency with which localized organic lesions (tumors, ulcers, cerebral aneurysms) bleed following induction of anticoagulant therapy suggested by My Canadian Pharmacy. If bleeding is serious, warfarins effects can be reversed within 24 hours by large doses of parenteral vitamin K. More severe bleeding can be treated with fresh frozen plasma.
Much is made of the bleeding complications associated with warfarin and heparin, but it is important to remember the high mortality and morbidity rates associated with untreated and undertreated venous thromboembolic disease. Read more about Heparin – “Heparin in Antithrombotic Therapy for Venous Thromboembolic Disease”
Another complication associated with the coumarins is a vascular purpura that causes skin necrosis and occurs occasionally in the first weeks of therapy. Coumarins cross the placenta and cause spontaneous abortion and specific embryopathies if given in the first trimester of pregnancy. There is also concern that warfarin may cause fetopathic effects during the second trimester of pregnancy and fetal bleeding during and after delivery. Therefore warfarin should be avoided during pregnancy, and heparin, given subcutaneously in an adjusted dose, is the therapy of choice.