Antithrombotic Therapy for Venous Thromboembolic Disease

I t 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 a pneumatic compression of the lower extremity. In this broad sense, thrombolytic agents are also antithrombotic, because they mediate the rapid dissolution of a formed thrombus (Table 1). The risk factors for venous thromboembolism and the effectiveness of antithrombotic agents in the treatment of established venous thrombotic disease will be described. Several of these agents are also useful for the primary prevention of venous thromboembolic disease, and this application of antithrombotic therapy will also be reviewed. Judgment of efficacy is based on the results of controlled clinical trials that either showed a statistically significant benefit or, if negative, were sufficiently large to exclude a clinically important benefit (level I study). Studies of lower quality will be designated level II or III. It must be emphasized that all antithrombotic therapy with either anticoagulants or platelet-active drugs is prophylactic, since these agents interrupt the progression of the thrombotic process; but unlike thrombolytic agents, they do not as a rule actively resolve it. Of the agents currently available in this country, only heparin, thrombolytic agents, and the coumarins in appropriate doses are used to treat established venous thromboembolic disease. Dextran and lower doses of heparmn and wai-farin are useful for prevention of disease, but these regimens are not appropriate for treatment of acute disease.