Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency.
Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency.
复制标题
先天性抗凝血酶缺乏症无症状患者血液中 Xa 因子活性升高。
DOI：
10.1172/jci112040
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Rosenberg,RD
中科院分区：
文献类型：
--
作者：
Bauer,KA;Goodman,TL;Kass,BL;Rosenberg,RD
先天性抗凝血酶缺乏症的存在一直被证明是易患静脉血栓形成的患者。我们已经利用凝血酶原片段F1+2放射免疫测定定量因子Xa活性在血液中的22个无症状的个人，这种临床疾病没有接受抗血栓治疗。与正常对照组相比，这些患者的F1+2平均水平显著升高（3.91 vs. 1.97 nM，P <0.001）。抗凝血酶缺乏者和正常人的~（131）I-F_（1 +2）代谢行为相似。通过F1+2试验测量的止血系统活动过度可通过将上述无症状个体的血浆抗凝血酶水平升高至正常范围来特异性校正。这项研究首次证明，血栓前状态可以被生化定义为人体循环中Xa因子酶活性的产生和抑制之间的不平衡。已知抗凝血酶和α 1-蛋白酶抑制剂（PI）是在不存在肝素的情况下人血浆中因子Xa的主要抑制剂。为了进一步评估抗凝血酶作为人类Xa因子抑制剂的机制，我们研究了5例表现出严重先天性α 1-PI缺陷的患者。我们的研究结果表明，这些受试者的血浆显示几乎相同的降低血浆抗凝血因子Xa活性的情况下，肝素相比，抗凝血酶缺乏的个人，但血浆F1+2水平在α 1-PI缺乏的人口没有显着不同，比正常。这些数据表明，α 1-PI在体内并不作为Xa因子的主要抑制剂，并且在人体中存在一种紧张性活性肝素依赖性机制，用于加速抗凝血酶对这种酶的中和。图片
The presence of congenital antithrombin deficiency has been consistently shown to predispose patients to venous thrombosis. We have utilized the prothrombin fragment F1+2 radioimmunoassay to quantitate factor Xa activity in the blood of 22 asymptomatic individuals with this clinical disorder not receiving antithrombotic therapy. The mean level of F1+2 was significantly elevated in these patients as compared to normal controls (3.91 vs. 1.97 nM, P less than 0.001). The metabolic behavior of 131 I-F1+2 was found to be similar in antithrombin-deficient subjects and normal individuals. The hemostatic system hyperactivity as measured by the F1+2 assay could be specifically corrected by raising the plasma antithrombin levels of the above asymptomatic individuals into the normal range. This study provides the first demonstration that the prethrombotic state can be biochemically defined as an imbalance between the production and inhibition of factor Xa enzymatic activity within the human circulation. It is known that antithrombin and alpha 1-proteinase inhibitor (PI) are the major inhibitors of factor Xa in human plasma in the absence of heparin. To further evaluate the mechanism by which antithrombin functions as an inhibitor of factor Xa in humans, we studied five patients who exhibited severe congenital deficiencies of alpha 1-PI. Our results indicated that the plasma of these subjects showed virtually identical decreases in plasma antifactor Xa activity in the absence of heparin when compared to antithrombin-deficient individuals, but the plasma F1+2 levels in the alpha 1-PI deficient population were not significantly different than normal. This data suggests that alpha 1-PI does not function as a major inhibitor of factor Xa in vivo, and that a tonically active heparin-dependent mechanism exists in humans for accelerating the neutralization of this enzyme by antithrombin.Images