Khan M M, Gikakis N, Miyamoto S, Rao A K, Cooper S L, Edmunds L H, Colman R W
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Ann Thorac Surg. 1999 Aug;68(2):473-8. doi: 10.1016/s0003-4975(99)00551-2.
Aprotinin reduces perioperative bleeding after open heart surgery, primarily by inhibiting fibrinolysis. In addition, the drug has both procoagulant and anticoagulant effects that involve complex reactions of coagulation proteins and cells that are incompletely understood. This study tests the hypothesis that aprotinin has an anticoagulant effect on the extrinsic coagulation pathway.
Human heparinized blood was recirculated through a membrane oxygenator with and without high concentrations of aprotinin (18.4 microM). Serial plasma samples were obtained at intervals up to 240 minutes.
Aprotinin significantly reduced the progressive increase in prothrombin fragments (F1.2) and thrombin-antithrombin complex beginning immediately. Aprotinin also significantly reduced monocyte expression of tissue factor and Mac-1. Aprotinin did not significantly reduce factor VII or factor VIIa.
During simulated cardiopulmonary bypass, aprotinin immediately inhibits kallikrein and thrombin formation via the intrinsic coagulation pathway. Later, aprotinin inhibits monocyte expression of tissue factor and the extrinsic coagulation pathway. The ability of aprotinin to inhibit monocyte tissue factor provides a means to reduce thrombin formation in blood aspirated from the wound during open heart surgery.
抑肽酶主要通过抑制纤维蛋白溶解来减少心脏直视手术后的围手术期出血。此外，该药物具有促凝血和抗凝血作用，涉及凝血蛋白和细胞的复杂反应，目前尚未完全了解。本研究检验抑肽酶对外源性凝血途径具有抗凝作用这一假设。
将人肝素化血液通过有和没有高浓度抑肽酶（18.4微摩尔）的膜式氧合器进行再循环。每隔一定时间直至240分钟采集系列血浆样本。
抑肽酶立即显著降低凝血酶原片段（F1.2）和凝血酶 - 抗凝血酶复合物的逐渐增加。抑肽酶还显著降低单核细胞组织因子和Mac-1的表达。抑肽酶未显著降低因子VII或因子VIIa。
在模拟体外循环期间，抑肽酶通过内源性凝血途径立即抑制激肽释放酶和凝血酶的形成。之后，抑肽酶抑制单核细胞组织因子的表达和外源性凝血途径。抑肽酶抑制单核细胞组织因子的能力为减少心脏直视手术期间从伤口吸出的血液中凝血酶的形成提供了一种方法。
