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.

Complications

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.

It has been recognized for over a century that stasis of blood, abnormalities of the vessel wall, and changes in the soluble and formed elements of the blood are the major contributors to thrombosis. For venous thrombosis, stasis and local alterations in blood elements are most important, since major pathologic changes are not routinely seen in the vessel wall at the nidus of a venous thrombus.

Several treatment regimens that modify one or more of these abnormalities may be antithrombotic. These modalities include drugs that inhibit blood coagulation, such as heparin and the coumarins, drugs that inhibit platelet function such as aspirin and dextran, and techniques that counteract venous stasis, such as pneumatic compression and electrical stimulation of lower extremity muscles (Table 1).