The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation.
The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation.
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DOI：
10.1182/blood.v70.2.343.343
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发表时间：
1987-08
期刊：
影响因子：
20.3
通讯作者：
K. Bauer;K. Bauer;R. Rosenberg;R. Rosenberg
中科院分区：
文献类型：
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作者：
K. Bauer;K. Bauer;R. Rosenberg;R. Rosenberg
许多研究人员推测，在血栓形成发作之前，人类体内存在一段时间的高凝状态。然而，事实证明，血栓前状态的明确生化定义是难以捉摸的，部分原因是缺乏监测血液凝固性相关变化的可靠技术。基于我们对凝血系统生物化学知识的最新进展，我们开发了一系列高灵敏度和特异性的免疫化学工具，可以在亚纳摩尔水平上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，分别测量 Xa 因子对凝血酶原分子的裂解和凝血酶-血栓调节蛋白复合物对蛋白 C 的裂解。 Nossel 和同事此前针对纤维蛋白肽 A (FPA) 和片段 B beta 1-42 构建了类似的检测方法，分别监测凝血酶对纤维蛋白原的裂解和纤溶酶对纤维蛋白 I 的蛋白水解。在患有弥散性血管内凝血的患者和许多患有急性深静脉血栓形成的受试者中发现这些标志物的水平显着升高。 F1+2 和 FPA 测定已被用来证明，在先天性缺乏抗凝血酶或蛋白 C 的非抗凝个体的血液中，因子 Xa 活性显着增加，但凝血酶活性不增加。已知这两种疾病与随后的血栓形成相关。还发现蛋白 C 缺乏症患者的蛋白 C 激活肽血浆水平显着降低。通过在术后患者的研究中使用FPA和Bβ1-42的免疫测定，已经表明凝血酶的促凝作用和纤溶酶对纤维蛋白I聚合物的抗凝作用之间的不平衡可能诱发获得性血栓形成素质。最后，我们最近证明，通过 F1+2 测定测量的凝血酶原激活可被血栓素质患者血液中的口服抗凝剂抑制。这些研究表明，这些测定技术可用于提高我们对高凝状态的理解，并开发更有效的治疗策略来预防血栓栓塞事件。
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.