Slaughter T F, LeBleu T H, Douglas J M, Leslie J B, Parker J K, Greenberg C S
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710.
Anesthesiology. 1994 Mar;80(3):520-6. doi: 10.1097/00000542-199403000-00007.
Prothrombin activation represents the key regulatory step in the hemostatic process. Once formed, thrombin contributes to the generation of fibrin as well as the activation of platelets and fibrinolysis. Failure to suppress thrombin formation during cardiac surgery could result in disorders of hemostasis and thrombosis in the perioperative period. The aim of this study was to determine the time course for prothrombin activation during the perioperative period associated with cardiac surgery.
We measured prothrombin activation during the perioperative period in 19 adult patients undergoing primary cardiac surgery using enzyme-linked immunosorbent assays for the detection of thrombin formation (prothrombin fragment 1.2 and thrombin-antithrombin III complex) and thrombin activity (fibrinopeptide A and fibrin monomer). Blood samples were obtained preoperatively; at 30-min intervals during cardiopulmonary bypass (CPB); and 1, 3, and 20 h after completion of CPB.
Despite anticoagulation with heparin, plasma concentrations of prothrombin fragment 1.2, thrombin-antithrombin III complex, and fibrin monomer increased throughout CPB. Peak concentrations for all hemostatic markers occurred in the samples obtained 3 h after completion of CPB. By the morning after surgery, plasma prothrombin fragment 1.2 returned to preoperative concentrations; however, fibrinopeptide A and fibrin monomer concentrations remained significantly increased (P < 0.05) compared to preoperative values.
These data clearly demonstrate the occurrence of prothrombin activation and thrombin activity during CPB despite heparin concentrations adequate to maintain the activated clotting time greater than 400 s. Hemostatic markers for the activation of prothrombin demonstrated peak concentrations 3 h after completion of CPB with a return to baseline concentrations by the morning after surgery. Markers for thrombin activity, however, suggest the presence of active thrombin through the morning after surgery. Further investigations will be necessary to determine the role of hemostatic activation in thrombotic complications after cardiac surgery.
凝血酶原激活是止血过程中的关键调控步骤。一旦形成,凝血酶会促进纤维蛋白的生成以及血小板的激活和纤维蛋白溶解。心脏手术期间未能抑制凝血酶的形成可能导致围手术期止血和血栓形成障碍。本研究的目的是确定心脏手术围手术期凝血酶原激活的时间进程。
我们使用酶联免疫吸附测定法检测凝血酶形成(凝血酶原片段1.2和凝血酶 - 抗凝血酶III复合物)和凝血酶活性(纤维蛋白肽A和纤维蛋白单体),对19例接受初次心脏手术的成年患者围手术期的凝血酶原激活情况进行了测量。术前采集血样;体外循环(CPB)期间每隔30分钟采集一次;CPB结束后1小时、3小时和20小时采集。
尽管使用肝素进行了抗凝,但在整个CPB过程中,血浆中凝血酶原片段1.2、凝血酶 - 抗凝血酶III复合物和纤维蛋白单体的浓度均升高。所有止血标志物的峰值浓度出现在CPB结束后3小时采集的样本中。术后次日早晨,血浆凝血酶原片段1.2恢复到术前浓度;然而,与术前值相比,纤维蛋白肽A和纤维蛋白单体浓度仍显著升高(P < 0.05)。
这些数据清楚地表明,尽管肝素浓度足以使活化凝血时间维持在大于400秒,但CPB期间仍发生了凝血酶原激活和凝血酶活性。凝血酶原激活的止血标志物在CPB结束后3小时达到峰值浓度,术后次日早晨恢复到基线浓度。然而,凝血酶活性标志物表明术后次日早晨仍存在活性凝血酶。需要进一步研究以确定止血激活在心脏手术后血栓形成并发症中的作用。