ALTERNATIVE TO HEPARIN ANTICOAGULATION

肝素抗凝的替代品

• 批准号: 6693733
• 负责人: KENNETH A SOLEN
• 金额: $ 28.89万
• 依托单位: THROMBODYNE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693733
• 关键词: bioengineering /biomedical engineering; biomaterial compatibility; biomedical equipment development; biomedical equipment safety; blood coagulation; blood filtration; clotting factor; embolism; extracorporeal circulation; heart /lung bypass; hemostasis; nonhuman therapy evaluation; surface coating; surface property; surgery material /equipment; swine

DESCRIPTION (provided by applicant): Anticoagulation of blood is necessary for prevention of clotting and/or thromboembolism during cardiopulmonary bypass or other procedures that require extracorporeal circulation. Conventionally, anticoagulation is achieved by administering heparin and reversed by neutralizing heparin with protamine. Both of these procedures may have potential pathological consequences. A subpopulation of patients is known to be sensitive to protamine, and heparin itself has been shown to cause thrombocytopenia in a subpopulation of patients undergoing open heart surgery. This is proposal to refine and develop an alternative to the heparin-protamine strategy. A novel device, termed clotting factor filter (CFF) has been developed that will bind and transiently remove clotting factors from circulating blood. Blood from which clotting factors have been removed would neither form clots nor thromboemboli during extracorporeal circulation, thus achieving the same effect as intended with heparin. Hypocoagulable blood gradually returns to normal state when the procedure is stopped, or recovery can be accelerated and normal hemostasis restored immediately by transfusion of autologous blood or plasma. Preliminary Phase I studies have confirmed the safety and efficacy of CFF approach. The objective of this Phase II proposal include: optimization of the CFF, characterization and performance of the optimized system, and verification that the CFF is able to effect appropriate 'anticoagulation' safely during cardiopulmonary bypass in an animal model. For the active matrix, linkers and base substrates will be investigated. For the plasma-matrix contact system, optimal column geometry will be selected, and a high-flow plasma separator will be designed. The optimal CFF system will be characterized to ascertain required level of 'anticoagulation' that will eliminate thrombosis during ECC. Finally, a porcine CPB model will be utilized to test the safety and efficacy of the CFF approach for 'anticoagulation' of blood during bypass. This will include careful assessment of hematologic and cardiovascular parameters during the procedure and during long term survival of the animal to assure that CFF approach is efficacious and safe.

描述（由申请人提供）：血液抗凝对于预防体外循环或其他需要体外循环的手术期间的凝血和/或血栓栓塞是必要的。传统上，抗凝作用是通过给予肝素来实现的，并通过用鱼精蛋白中和肝素来逆转。这两种手术都可能产生潜在的病理后果。已知有一部分患者对鱼精蛋白敏感，而肝素本身已被证明会导致一部分接受心脏直视手术的患者出现血小板减少症。这是完善和开发肝素-鱼精蛋白策略替代方案的提案。一种称为凝血因子过滤器（CFF）的新型装置已经开发出来，它可以结合并暂时去除循环血液中的凝血因子。去除了凝血因子的血液在体外循环时既不会形成凝块，也不会形成血栓栓塞，从而达到与肝素相同的效果。当手术停止时，低凝血液逐渐恢复正常状态，或者通过输入自体血或血浆可以加速恢复并立即恢复正常止血。初步 I 期研究已证实 CFF 方法的安全性和有效性。该第二阶段提案的目标包括：优化 CFF、优化系统的表征和性能，以及验证 CFF 能够在动物模型的体外循环期间安全地实现适当的“抗凝”。对于有源矩阵，将研究连接体和基础基底。对于等离子体-基质接触系统，将选择最佳的柱几何形状，并设计高流量等离子体分离器。最佳 CFF 系统的特点是确定所需的“抗凝”水平，从而消除 ECC 期间的血栓形成。最后，将利用猪 CPB 模型来测试 CFF 方法在搭桥期间“抗凝”血液的安全性和有效性。这将包括在手术期间和动物长期生存期间仔细评估血液学和心血管参数，以确保 CFF 方法有效且安全。