Bauer K A, Rosenberg R D
Blood. 1987 Aug;70(2):343-50.
Numerous investigators have postulated that a hypercoagulable state exists in humans for a period of time before the development of thrombotic episodes. A clear biochemical definition of the prethrombotic state, however, has proved elusive due in part to the lack of reliable techniques for monitoring pertinent changes in blood coagulability. Based on recent advances in our knowledge of the biochemistry of the coagulation system, a series of highly sensitive and specific immunochemical tools has been developed that can quantitate the activities of various steps of the hemostatic mechanism in vivo at the subnanomolar level. We have established assays for F1+2 and the protein C activation peptide, which measure the cleavage of the prothrombin molecule by factor Xa and the scission of protein C by the thrombin-thrombomodulin complex, respectively. Nossel and coworkers had previously constructed similar assays for fibrinopeptide A (FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by thrombin and the proteolysis of fibrin I by plasmin, respectively. Substantial elevations in the levels of these markers have been found in patients with disseminated intravascular coagulation and many subjects with acute deep venous thrombosis. The F1+2 and FPA assays have been used to demonstrate that significant increments in factor Xa activity but not thrombin activity regularly occur in the blood of nonanticoagulated individuals with congenital deficiencies of antithrombin or protein C. These two disorders are known to be correlated with the subsequent development of thrombosis. Patients with protein C deficiency have also been noted to have significantly reduced plasma levels of protein C activation peptide. By using the immunoassays for FPA and B beta 1-42 in studies of postoperative patients, it has been shown that an imbalance between the procoagulant action of thrombin and the anticoagulant effect of plasmin on fibrin I polymer may induce an acquired thrombotic diathesis. Finally, we have recently demonstrated that prothrombin activation as measured by the F1+2 assay is suppressed by oral anticoagulants in the blood of patients with thrombotic diatheses. These investigations suggest that these assay techniques can be used to improve our understanding of the hypercoagulable state as well as to develop more effective treatment strategies for the prevention of thromboembolic events.
许多研究人员推测，在血栓形成发作之前的一段时间内，人类存在高凝状态。然而，由于缺乏监测血液凝固性相关变化的可靠技术，血栓前状态的明确生化定义一直难以捉摸。基于我们对凝血系统生物化学知识的最新进展，已开发出一系列高度敏感和特异的免疫化学工具，可在亚纳摩尔水平定量体内止血机制各个步骤的活性。我们已经建立了F1+2和蛋白C激活肽的检测方法，分别用于测量因子Xa对凝血酶原分子的裂解以及凝血酶-血栓调节蛋白复合物对蛋白C的裂解。诺塞尔及其同事此前曾构建过类似的纤维蛋白肽A（FPA）和Bβ1-42片段的检测方法，分别用于监测凝血酶对纤维蛋白原的裂解以及纤溶酶对纤维蛋白I的蛋白水解。在弥散性血管内凝血患者和许多急性深静脉血栓形成的受试者中，已发现这些标志物的水平显著升高。F1+2和FPA检测方法已被用于证明，在抗凝血酶或蛋白C先天性缺乏的未抗凝个体的血液中，因子Xa活性会显著增加，但凝血酶活性不会。已知这两种疾病与随后的血栓形成有关。还注意到蛋白C缺乏的患者血浆中蛋白C激活肽水平显著降低。通过在术后患者研究中使用FPA和Bβ1-42的免疫测定法，已表明凝血酶的促凝作用与纤溶酶对纤维蛋白I聚合物的抗凝作用之间的失衡可能会诱发获得性血栓形成素质。最后，我们最近证明，在血栓形成素质患者的血液中，口服抗凝剂可抑制通过F1+2检测法测得的凝血酶原激活。这些研究表明，这些检测技术可用于增进我们对高凝状态的理解，并制定更有效的预防血栓栓塞事件的治疗策略。
