Brister S J, Ofosu F A, Buchanan M R
Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 1993 Aug 2;70(2):259-62.
Blood samples were collected from 43 patients undergoing elective cardiac surgery to determine the extent of thrombin generation and inhibition in patients when receiving heparin while undergoing cardiopulmonary bypass (CPB). Plasma prothrombin fragment F1 + 2 and thrombin-antithrombin III (TAT) levels were measured as markers of thrombin generation and inhibition, respectively. Both F1 + 2 and TAT levels increased significantly during the course of CPB despite the heparin causing significant systemic anticoagulation, i.e. the activated coagulation time (ACT) was prolonged to greater than 400 s throughout the entire surgical procedure. The extent of thrombin generation increased with time on CPB but did not differ between patients receiving normothermic and hypothermic cardioplegia during CPB. Furthermore, thrombin generation increased following the neutralization of the heparin with protamine sulphate, and continued to be elevated significantly 24 h post surgery. The observation that high dose heparin did not prevent thrombin generation during CPB, is consistent with previous experimental studies demonstrating that thrombin bound to fibrin or other surfaces (e.g. the CPB conduit) is resistant to antithrombin III/heparin inhibition, and thus able to facilitate further thrombin generation. The observation that thrombin generation continued to be elevated post surgery i.e. 24 h after neutralizing the heparin with protamine sulphate, suggests that the high dose heparin did not inhibit effectively all of the thrombin that had been generated. Thus, CPB patients may be at risk not only of bleeding and other side-effects associated with the acute use of high dose heparin, but may also be at risk of further thrombosis-related events either acutely or chronically.
采集了43例接受择期心脏手术患者的血样，以确定患者在体外循环（CPB）期间接受肝素时凝血酶生成和抑制的程度。分别测量血浆凝血酶原片段F1 + 2和凝血酶 - 抗凝血酶III（TAT）水平作为凝血酶生成和抑制的标志物。尽管肝素引起了显著的全身抗凝作用，即整个手术过程中活化凝血时间（ACT）延长至大于400秒，但在CPB过程中F1 + 2和TAT水平均显著升高。凝血酶生成的程度随CPB时间的延长而增加，但在CPB期间接受常温与低温心脏停搏的患者之间没有差异。此外，用硫酸鱼精蛋白中和肝素后凝血酶生成增加，并且在术后24小时仍持续显著升高。高剂量肝素在CPB期间不能预防凝血酶生成这一观察结果，与先前的实验研究一致，这些研究表明与纤维蛋白或其他表面（如CPB管道）结合的凝血酶对抗凝血酶III /肝素抑制具有抗性，因此能够促进进一步的凝血酶生成。在用硫酸鱼精蛋白中和肝素后24小时即术后凝血酶生成持续升高这一观察结果表明，高剂量肝素不能有效抑制所有已生成的凝血酶。因此，CPB患者不仅可能面临与急性使用高剂量肝素相关的出血和其他副作用风险，还可能急性或慢性地面临进一步血栓形成相关事件的风险。
