Koster Andreas, Fischer Thomas, Gruendel Marcus, Mappes Andreas, Kuebler Wolfgang M, Bauer Matthias, Kuppe Herman
Department of Anesthesia, Deutsches Herzzentrum Berlin, Germany.
J Cardiothorac Vasc Anesth. 2003 Apr;17(2):171-5. doi: 10.1053/jcan.2003.42.
Attenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB.
A randomized, prospective clinical investigation.
A major European heart center.
Five groups with 20 patients each were investigated.
The groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion.
There were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss.
Activation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.
在体外循环（CPB）期间，减弱止血激活是一个核心目标。然而，这给对肝素不敏感的患者带来了问题。本研究旨在评估在CPB期间管理肝素抵抗患者的不同策略。
一项随机、前瞻性临床研究。
欧洲一家大型心脏中心。
对五组患者进行研究，每组20例。
各小组处理如下：（1）维持目标活化凝血时间（ACT）；（2）维持目标普通肝素（UFH）水平，并采用基于UFH水平的策略补充（3）抗凝血酶III（AT III）、（4）直接凝血酶抑制剂重组水蛭素（r - hirudin）或（5）短效血小板糖蛋白（GP）IIb/IIIa拮抗剂替罗非班。评估血小板计数以及接触因子XIIa、凝血酶和可溶性纤维蛋白的生成情况。在CPB前以及CPB后鱼精蛋白输注前采集样本。
在因子XIIa的生成方面未观察到差异。与ACT管理相比，基于UFH的策略以及补充AT III、r - hirudin和替罗非班导致凝血酶生成显著减少（p < 0.05）。仅在接受AT III、r - hirudin或替罗非班补充至UFH的患者中观察到纤维蛋白形成显著减少。与其他组相比，替罗非班的给药导致血小板计数显著保留。术后失血量无显著差异。
肝素抵抗患者在CPB期间的止血激活很可能归因于组织因子途径的刺激。即使仅使用高浓度的UFH也不能有效抑制这种激活。因此，对于这些患者，在CPB期间用UFH进行抗凝时应补充AT III、短效直接凝血酶抑制剂或短效血小板糖蛋白IIb/IIIa拮抗剂。
