PLATELET-HEPARIN INTERACTIONS IN CARDIOVASCULAR SURGERY

心血管手术中的血小板-肝素相互作用

• 批准号: 3471854
• 负责人: MICHAEL SOBEL
• 金额: $ 8.31万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3471854
• 关键词: affinity labeling; anticoagulants; antithrombin III; blood proteins; calcium; cardiovascular surgery; chemical binding; extracorporeal circulation; heparin; human subject; membrane activity; platelet aggregation; receptor; receptor binding

Platelet agggregation and adhesion are primary events in normal hemostasis and in the contact of blood with artificial surfaces. Because heparin is a potent inhibitor of the plasma coagulation system, it is widely used to treat or prevent thrombosis during cardiovascular surgery and extracoporeal circulation. However, heparin does not significantly inhibit platelet activation and may paradoxically stimulate platelets. The interactions between heparin and platelets may produce the serious complications of bleeding or immune thrombocytopenia. Many artificial surfaces bonded with heparin are not truly non-thrombogenic, and remain platelet reactive. We hypothesize that platelets have specific heparin binding sites which determine many of the unique interactions between heparin and platelets. Our own preliminary research does suggest the presence of heparin binding sites on the platelet surface, and indicates that platelet activation may enchance heparin binding. Our work, and that of others indicate that certain regions of the heparin molecule are preferentially bound, and that heparin binding affects platelet behavior. We propose to characterize the platelet surface receptors for heparin and to determine the physiologic and biochemical conditions which influence heparin binding, using a novel platelet- heparin binding assay. We plan to identify these binding sites using photoaffinity labelling techniques. We will study the binding of precisely characterized heparin fractions to determine the distinctive regions of the heparin molecule which promote binding. Finally, using these fractions we will study heparin- mediated platelet aggregation and correlate heparin binding with the functional effects of heparin on platelets. Our long range goals are to apply these basic scientific techniques to the study of platelet-heparin interactions in clinical patients, and to identify heparin species which are less platelet reactive, but are effective antithrombotic agents.

血小板聚集和粘附是正常情况下的主要事件