PLATELET-HEPARIN INTERACTIONS IN CARDIOVASCULAR SURGERY

血小板聚集和粘附是正常人血小板聚集和粘附的主要事件。 止血和血液与人造表面接触。 因为肝素是血浆凝固的有效抑制剂 系统，它被广泛用于治疗或预防血栓形成期间 心血管手术和体外循环。 然而，在这方面， 肝素不显著抑制血小板活化， 反而刺激血小板。 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无血栓形成， 血小板反应性。 我们假设血小板具有特异性肝素结合位点 这决定了肝素和 和血小板。 我们自己的初步研究确实表明， 血小板表面存在肝素结合位点，以及 表明血小板活化可增强肝素结合。 我们和其他人的工作表明， 肝素分子优先结合，肝素 结合影响血小板行为。 我们建议表征血小板表面受体， 肝素，并测定生理和生化 影响肝素结合的条件，使用新的血小板- 肝素结合测定。 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 精确表征的肝素组分，以确定 肝素分子的独特区域， 约束力 最后，我们将使用这些馏分研究肝素- 介导的血小板聚集和相关肝素结合 肝素对血小板的功能作用。 我们的长期目标是应用这些基本的科学技术 临床患者中血小板-肝素相互作用的研究， 并鉴定血小板反应性较低的肝素种类， 而是有效的抗血栓形成剂。

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.