Gruenwald Colleen E, Manlhiot Cedric, Crawford-Lean Lynn, Foreman Celeste, Brandão Leonardo R, McCrindle Brian W, Holtby Helen, Richards Ross, Moriarty Helen, Van Arsdell Glen, Chan Anthony K
Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, Canada.
J Extra Corpor Technol. 2010 Mar;42(1):9-19.
Cardiopulmonary bypass (CPB) creates a pro-coagulant state by causing platelet activation and inflammation leading to thrombin generation and platelet dysfunction. It is associated with severe derangements in normal homeostasis resulting in both thrombotic and hemorrhagic complications. This derangement is greater in children with congenital heart disease than in adults because of the immaturity of the coagulation system, hemodilution of coagulation factors, hyperreactive platelets, and in some patients, physiologic changes associated with cyanosis. During CPB, an appropriate amount of heparin is given with the goal of minimizing the risk of thrombosis and platelet activation and at the same time reducing the risk of bleeding from over anticoagulation. In young children, this balance is more difficult to achieve because of inherent characteristics of the hemostatic system in these patients. Historically, protocols for heparin dosing and monitoring in children have been adapted from adult protocols without re-validation for children. Extreme hemodilution of coagulation factors and platelets in young children affects the accuracy of anticoagulation monitoring in children. The activated clotting time does not correlate with plasma levels of heparin. In addition, recent studies suggest that children need larger doses of heparin than adults, because they have lower antithrombin levels, and they metabolize heparin more rapidly. Preliminary studies demonstrated that the use of individualized heparin and protamine monitoring and management in children is associated with reduced platelet activation and dysfunction and improved clinical outcomes. However, this review article clearly establishes that further studies are necessary to obtain evidence-based protocols for the proper management of anticoagulation of children undergoing cardiopulmonary bypass.
体外循环(CPB)通过引起血小板活化和炎症反应导致凝血酶生成及血小板功能障碍,从而产生促凝状态。它与正常内环境稳态的严重紊乱相关,可导致血栓形成和出血并发症。由于凝血系统不成熟、凝血因子血液稀释、血小板反应性过高,以及在某些患者中与紫绀相关的生理变化,先天性心脏病患儿的这种紊乱比成人更为严重。在体外循环期间,给予适量肝素的目的是将血栓形成和血小板活化的风险降至最低,同时降低过度抗凝导致出血的风险。在幼儿中,由于这些患者止血系统的固有特性,更难实现这种平衡。从历史上看,儿童肝素给药和监测方案是从成人方案改编而来,未对儿童进行重新验证。幼儿凝血因子和血小板的极度血液稀释会影响儿童抗凝监测的准确性。活化凝血时间与肝素血浆水平不相关。此外,最近的研究表明,儿童比成人需要更大剂量的肝素,因为他们抗凝血酶水平较低,且肝素代谢更快。初步研究表明,在儿童中使用个体化肝素和鱼精蛋白监测及管理与血小板活化和功能障碍的减少以及临床结果的改善相关。然而,这篇综述文章明确指出,有必要进行进一步研究,以获得基于证据的方案,用于正确管理接受体外循环的儿童的抗凝治疗。