Dahl O E
Department of Orthopaedic Surgery, Ullevaal University Hospital, Oslo, Norway.
J Cardiothorac Vasc Anesth. 1997 May;11(3):322-8. doi: 10.1016/s1053-0770(97)90102-6.
Cardiac surgery and hip replacement surgery (HRS) are associated with serious cardiorespiratory and vascular complications. Activation of blood coagulation and fibrinolysis in the lung vasculature seem to play a key role in the pathophysiology of this process. This article reviews the results of several experimental and clinical studies within this field. Animal studies have shown that bone traumatization induces a marked local activation of coagulation and fibrinolysis in femoral vein blood draining from the surgical area as shown by a 2.5-fold increase in plasma levels of thrombin-antithrombin complexes (TAT) and a seven-fold increase in tissue plasminogen activator (tPA) activity. A slight increase in TAT in femoral vein blood on the unoperated side has also been found and indicates increased activation of coagulation in recirculated blood, which had passed the pulmonary microvasculature. In addition, human studies have shown that bone preparation induced a 200-fold increase in systemic circulating fibrinopeptide-A during surgery and a five-fold increase in TAT (when thromboprophylaxis was stopped 1 week after surgery). Both increases are markers of thrombin generation. Furthermore, cellular studies have shown that thrombin and certain cytotoxic chemicals, such as methylmethacrylate monomer (bone cement), separately and together trigger monocytes to tissue factor (TF) expression and cause endothelial cell shape changes and detachment. This may allow pericellular fibrin formation to occur on monocytes and also transforms the nonthrombogenic endothelial coverage into a highly thrombogenic surface that triggers the conversion of fibrinogen to fibrin and releases fibrinopeptide-A. Finally, sequestration of granulocytes caused release of autodigestive proteases, which may have further strengthened this procoagulant process. Synchronous to the massive intrapulmonary activation of coagulation, an increased fibrinolytic activity was found, as evidenced by a marked drop in arterial blood tPA during surgery. This indicated tPA binding to fibrin deposits in the lung capillaries. However, this clearing process, to obtain adequate blood flow and gas exchange, was shut down several hours after surgery by an antifibrinolytic activity (PAI-1). Thus, these studies indicated that bone surgery induces a substantial intraoperative hemostatic activation in the lung capillaries, which is the primary target organ for venous blood-borne bone-marrow debris. Soft-tissue surgery and vascular surgery seem to induce less systemic activation of coagulation and fibrinolysis.
心脏手术和髋关节置换手术（HRS）与严重的心肺和血管并发症相关。肺血管系统中凝血和纤溶的激活似乎在这一过程的病理生理学中起关键作用。本文综述了该领域内多项实验和临床研究的结果。动物研究表明，骨创伤会导致手术区域引流的股静脉血中凝血和纤溶显著局部激活，凝血酶 - 抗凝血酶复合物（TAT）血浆水平增加2.5倍以及组织纤溶酶原激活物（tPA）活性增加7倍就表明了这一点。在未手术一侧的股静脉血中也发现TAT略有增加，这表明通过肺微血管的再循环血液中凝血激活增加。此外，人体研究表明，在手术期间，骨制备会使全身循环纤维蛋白肽 - A增加200倍，TAT增加5倍（术后1周停止血栓预防时）。这两种增加都是凝血酶生成的标志物。此外，细胞研究表明，凝血酶和某些细胞毒性化学物质，如甲基丙烯酸甲酯单体（骨水泥），单独或共同触发单核细胞表达组织因子（TF），并导致内皮细胞形态改变和脱离。这可能使单核细胞表面形成细胞周围纤维蛋白，并将非血栓形成的内皮覆盖转化为高度血栓形成的表面，从而触发纤维蛋白原转化为纤维蛋白并释放纤维蛋白肽 - A。最后，粒细胞的隔离导致自消化蛋白酶的释放，这可能进一步加强了这种促凝过程。与肺内大量凝血激活同步，发现纤溶活性增加，手术期间动脉血tPA显著下降就证明了这一点。这表明tPA与肺毛细血管中的纤维蛋白沉积物结合。然而，为了获得足够的血流和气体交换的这种清除过程在手术后数小时被抗纤溶活性（PAI - 1）关闭。因此，这些研究表明，骨手术会在肺毛细血管中引起大量术中止血激活，肺毛细血管是静脉血源性骨髓碎片的主要靶器官。软组织手术和血管手术似乎引起的凝血和纤溶全身激活较少。
