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）：在心肺转流术或其他需要体外循环的手术中，血液抗凝是预防凝血和/或血栓栓塞的必要条件。常规地，抗凝作用通过施用肝素来实现，并且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。已知患者亚群对鱼精蛋白敏感，并且肝素本身已被证明在接受心脏直视手术的患者亚群中引起血小板减少。这是一项改进和开发肝素-鱼精蛋白策略的替代方案的建议。一种新的装置，称为凝血因子过滤器（CFF）已经开发出来，将结合和短暂地从循环血液中去除凝血因子。去除凝血因子的血液在体外循环过程中既不会形成凝块，也不会形成血栓栓塞，从而达到与肝素预期相同的效果。当手术停止时，低凝血液逐渐恢复正常状态，或通过回输自体血或血浆可加速恢复，立即恢复正常止血。初步的I期研究已经证实了CFF方法的安全性和有效性。本II期提案的目标包括：CFF的优化、优化系统的表征和性能，以及验证CFF能够在动物模型的心肺转流期间安全地实现适当的“抗凝”。对于有源矩阵，将研究连接器和基底。对于血浆-基质接触系统，将选择最佳柱几何形状，并设计高流量血浆分离器。将对最佳CFF系统进行表征，以确定ECC期间消除血栓形成所需的“抗凝”水平。最后，将使用猪CPB模型来测试CFF方法在旁路期间用于血液“抗凝”的安全性和有效性。这将包括在手术期间和动物长期存活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。