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[心脏手术体外循环中肝素和鱼精蛋白抗凝的替代方法]

[Alternatives to heparin and protamine anticoagulation for cardiopulmonary bypass in cardiac surgery].

作者信息

Bouraghda Aurore, Gillois Pierre, Albaladejo Pierre

机构信息

Pôle Anesthésie-Réanimation, UJF-Grenoble, Grenoble, France,

出版信息

Can J Anaesth. 2015 May;62(5):518-28. doi: 10.1007/s12630-015-0339-6. Epub 2015 Feb 20.

Abstract

PURPOSE

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis.

SOURCE

A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the "Cochrane collaboration Handbook". Twenty articles were analyzed. The Thériaque database from the University Hospital of Grenoble made the economic analysis possible.

PRINCIPAL FINDINGS

Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin.

CONCLUSIONS

The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.

摘要

目的

肝素抗凝后用鱼精蛋白逆转常用于体外循环(CPB)心脏手术,但该策略存在一些局限性。本研究的主要目的是确定心脏手术CPB期间可靠的抗凝替代方法。对于每种提出的药物,次要目的是概述其主要优缺点,提出治疗方案,并进行成本效益分析。

来源

2012年9月至2013年12月进行了文献系统综述。该综述基于“Cochrane协作手册”制定的方案。分析了20篇文章。格勒诺布尔大学医院的Thériaque数据库使经济分析成为可能。

主要发现

考虑了七种替代抗凝策略:达那肝素钠、比伐卢定、阿加曲班、水蛭素、安克洛酶、依达肝素和EP217609。达那肝素钠存在个体差异问题。多项研究(EVOLUTION - ON、CHOOSE - ON)提出了比伐卢定可靠的治疗方案。安克洛酶导致血液制品输注增加。直接凝血酶抑制剂提供了一种有前景的替代方法。EP217609是一种目前正在进行IIa期临床试验的合成抗凝剂。它是Xa因子的间接抑制剂,游离和结合凝血酶的直接抑制剂,可被抗生物素蛋白中和。

结论

不存在用于CPB心脏手术的理想抗凝策略。肝素和鱼精蛋白仍然是抗凝治疗的金标准。迄今为止,尽管比伐卢定成本高且缺乏现成的拮抗剂,但它是最有前景的分子。

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