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Platelet-Active Agents in the Management of Thrombotic Disorders

  • Laurence A. Harker
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

At present there is intense interest in aspirin therapy for vascular disease. Aspirin has been shown in well-designed clinical trails to be beneficial in five and possibly six clinical settings relevant to cardiovascular disease: (1) reduction of thromboembolic complications associated with artificial heart valves; (2) prevention of stroke and death in men with transient ischemic attacks; (3) decrease in thrombotic occlusion of arteriovenous silastic cannula in uremic patients undergoing hemodialysis; (4) reduction in myocardial infarction in patients with unstable angina; (5) probably in the secondary prevention of acute myocardial infarction; and (6) possibly to increase the patency of saphenous vein coronary bypass grafts, although this report requires confirmation. These reported benefits of aspirin require some comment. First, the antithrombotic effects of aspirin in patients with prosthetic mitral valves was evident in association with oral anticoagulant therapy, a combination that is associated with an unacceptably high frequency of gastrointestinal bleeding. Second, the capacity of aspirin in low doses to reduce the thrombotic complications of arteriovenous cannula was shown in patients undergoing chronic hemodialysis and thus associated with significant platelet dysfunction. It cannot be assumed that a similar dose would be antithrombotic in the absence of underlying platelet dysfunction. Third, the pathogenetic mechanisms of TIA and unstable angina may not be thrombotic but vasospastic. Thus, the benefits of aspirin in those clinical settings may reflect blockade of TxA2-mediated vasospasm rather than inhibition of platelet-dependent thrombus formation. Fourth, the results of aspirin in secondary prevention of acute MI is not statistically conclusive. Sulfinpyrazone reduces A-V cannula occlusion, early coronary artery saphenous vein graft occlusion, and possibly sudden death following myocardial infarction. It may also decrease thromboembolism in patients with substitute heart valves. Dipyridamole decreases thromboembolism in patients with artificial heart valves (in combination with anticoagulants), and in combination with aspirin it has been shown to reduce both early and late coronary artery saphenous vein graft occlusion and to preserve renal function in patients with membranoproliferative glomerulonephritis. The relative importance of the combination versus each drug given individually remains to be established.

Keywords

Unstable Angina Oral Anticoagulant Therapy Membranoproliferative Glomerulonephritis Thromboembolic Stroke Artificial Heart Valve 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Laurence A. Harker
    • 1
  1. 1.Department of Basic and Clinical ResearchScripps Clinic and Research FoundationLa JollaUSA

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