Gikakis N, Khan M M, Hiramatsu Y, Gorman J H, Hack C E, Sun L, Rao A K, Niewiarowski S, Colman R W, Edmunds L H
Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, USA.
Circulation. 1996 Nov 1;94(9 Suppl):II341-6.
Even when large doses of heparin are administered during cardiopulmonary bypass, thrombin is produced. Thrombin is a powerful protease that is associated with the thrombotic and bleeding complications of open heart surgery and is produced by cleavage of prothrombin by factor Xa. This study assessed the ability of a specific inhibitor of factor Xa, recombinant tick anticoagulant peptide (rTAP), alone or in combination with standard heparin and a low-molecular-weight heparin, enoxaparin, to suppress thrombin formation and activity during in vitro extracorporeal circulation.
Fresh, anticoagulated human blood was recirculated for 2 hours in an extracorporeal membrane oxygenator perfusion circuit at 37 degrees C. Four anticoagulant protocols were evaluated; porcine heparin (3.75 U/mL); enoxaparin (17.5 U/mL); rTAP (4 mumol/L); and porcine heparin plus rTAP (2 mumol/L). Blood samples were obtained for analysis from the donor, after anticoagulation, and after 5, 30, 60, and 120 minutes of recirculation. There were no significant differences between groups in platelet count, response to adenosine diphosphate, or prothrombin fragment (F1.2) production. rTAP plus heparin reduced beta-thromboglobulin release; fibrinopeptide A concentrations were significantly higher with rTAP alone. Enoxaparin strongly and significantly inhibited complement C5b9 production and neutrophil elastase release and was associated with significantly increased concentrations of C1-C1 inhibitor and kallikrein-C1 inhibitor complexes.
rTAP does not reduce thrombin formation or activity during in vitro extracorporeal circulation. Enoxaparin markedly inhibits formation of the complement membrane attack complex and neutrophil elastase release, possibly by accelerating C1 inhibitor activity.
即使在体外循环期间给予大剂量肝素，仍会产生凝血酶。凝血酶是一种强大的蛋白酶，与心脏直视手术的血栓形成和出血并发症相关，它是由因子Xa切割凝血酶原产生的。本研究评估了因子Xa的特异性抑制剂重组蜱抗凝血肽（rTAP）单独使用或与标准肝素及低分子量肝素依诺肝素联合使用时，在体外循环期间抑制凝血酶形成和活性的能力。
新鲜抗凝人血在37℃的体外膜肺氧合灌注回路中再循环2小时。评估了四种抗凝方案；猪肝素（3.75 U/mL）；依诺肝素（17.5 U/mL）；rTAP（4 μmol/L）；以及猪肝素加rTAP（2 μmol/L）。在抗凝后以及再循环5、30、60和120分钟后从供血者处采集血样进行分析。各组之间在血小板计数、对二磷酸腺苷的反应或凝血酶原片段（F1.2）产生方面无显著差异。rTAP加肝素减少了β-血小板球蛋白释放；单独使用rTAP时纤维蛋白肽A浓度显著更高。依诺肝素强烈且显著地抑制补体C5b9产生和中性粒细胞弹性蛋白酶释放，并与C1-C1抑制剂和激肽释放酶-C1抑制剂复合物浓度显著增加相关。
rTAP在体外循环期间不会减少凝血酶的形成或活性。依诺肝素显著抑制补体膜攻击复合物的形成和中性粒细胞弹性蛋白酶释放，可能是通过加速C1抑制剂活性实现的。
