PLATELET-HEPARIN INTERACTIONS IN CARDIOVASCULAR SURGERY

血小板聚集和黏附是正常人的主要事件 止血和血液与人工表面的接触。 因为肝素是一种有效的血浆凝血抑制物 系统，它被广泛用于治疗或预防血栓形成 心血管手术和体外循环。然而， 肝素不能显著抑制血小板活化，可能 自相矛盾地刺激血小板。两国之间的相互作用 肝素和血小板可能会产生严重的并发症 出血或免疫性血小板减少症。许多人造表面 与肝素结合并不是真正的非血栓形成，而且仍然 血小板反应。 我们假设血小板有特定的肝素结合部位。 它们决定了肝素之间的许多独特的相互作用 还有血小板。我们自己的初步研究确实表明 在血小板表面存在肝素结合部位，以及 提示血小板活化可增强肝素结合力。 我们的工作，以及其他人的工作表明，地球的某些区域 肝素分子优先结合，且肝素 结合会影响血小板的行为。 我们建议对血小板表面受体进行表征，以 肝素与生理生化指标的测定 影响肝素结合的条件，使用一种新的血小板- 肝素结合试验。我们计划确定这些结合位点 使用光亲和标记技术。我们将研究这种约束 精确表征的肝素组分以确定 肝素分子的独特区域促进 有约束力的。最后，利用这些组分，我们将研究肝素- 介导的血小板聚集及其与肝素结合的相关性 肝素对血小板功能的影响。 我们的长期目标是应用这些基本的科学技术 对于临床患者的血小板-肝素相互作用的研究， 并确定哪些肝素的血小板反应性较低， 但都是有效的抗血栓药。

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.