Kojima T, Gando S, Morimoto Y, Mashio H, Goda Y, Kawahigashi H, Kemmotsu O
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Thromb Res. 2001 Dec 1;104(5):301-7. doi: 10.1016/s0049-3848(01)00379-6.
The aim of this study was to systematically elucidate the effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass (CPB) surgery. Twenty-two patients undergoing CPB surgery were randomized to receive 100 mg/kg tranexamic acid or an equal volume of saline after anesthesia induction and prior to skin incision. Plasma levels of tissue plasminogen activator (t-PA) antigen and activity, crosslinked fibrin degradation products (D-dimer), alpha2-antiplasmin-plasmin complex, and plasminogen activator inhibitor-1 (PAI-1) antigen were measured. Blood samples were obtained after induction of anesthesia, before, during, and after CPB, at the end of surgery, and the next morning after surgery. Intraoperative and postoperative blood loss during 24 h after surgery was recorded. Patients' demographics were similar between the two groups. No patients suffered from thrombotic complications after surgery. In the tranexamic acid group, fibrinolytic activity and secondary fibrinolysis as measured by t-PA activity and D-dimer were markedly suppressed during CPB surgery (P=.042 and P=.015, respectively). Decreased fibrinolytic activity and fibrinolysis were accompanied by reduction of perioperative bleeding in the tranexamic acid group. We could also find a good positive correlation between the peak levels of t-PA activity and D-dimer (r(2)=.4203, P=.0011). No differences in the t-PA antigen, PAI-1 antigen release, and plasmin inhibition by alpha2-antiplasmin were apparent between the two groups. In a randomized, prospective trial of patients undergoing CPB surgery, we demonstrated that the synthetic antifibrinolytic drug tranexamic acid effectively suppresses fibrinolysis by inhibiting t-PA and plasmin activity with clear reduction of perioperative blood loss. While tranexamic acid had no effects on the other important fibrinolytic inhibitors like PAI-1 and alpha2-antiplasmin.
本研究的目的是系统阐明氨甲环酸对体外循环（CPB）手术期间及术后纤维蛋白溶解和出血的影响。22例接受CPB手术的患者在麻醉诱导后、皮肤切开前被随机分为两组，分别接受100mg/kg氨甲环酸或等体积生理盐水。检测血浆组织型纤溶酶原激活物（t-PA）抗原及活性、交联纤维蛋白降解产物（D-二聚体）、α2-抗纤溶酶-纤溶酶复合物和纤溶酶原激活物抑制剂-1（PAI-1）抗原水平。于麻醉诱导后、CPB前、CPB期间、CPB后、手术结束时及术后次日清晨采集血样。记录术后24小时内的术中及术后失血量。两组患者的人口统计学特征相似。术后无患者发生血栓并发症。在氨甲环酸组，CPB手术期间通过t-PA活性和D-二聚体测量的纤维蛋白溶解活性和继发性纤维蛋白溶解明显受到抑制（分别为P = 0.042和P = 0.015）。氨甲环酸组纤维蛋白溶解活性和纤维蛋白溶解降低，同时围手术期出血减少。我们还发现t-PA活性和D-二聚体的峰值水平之间存在良好的正相关（r² = 0.4203，P = 0.0011）。两组之间t-PA抗原、PAI-1抗原释放以及α2-抗纤溶酶对纤溶酶的抑制作用无明显差异。在一项针对接受CPB手术患者的随机前瞻性试验中，我们证明合成抗纤溶药物氨甲环酸通过抑制t-PA和纤溶酶活性有效抑制纤维蛋白溶解，围手术期失血量明显减少。而氨甲环酸对其他重要的纤维蛋白溶解抑制剂如PAI-1和α2-抗纤溶酶没有影响。
