Activation of human factor VII in the initiation of tissue factor-dependent coagulation.
Activation of human factor VII in the initiation of tissue factor-dependent coagulation.
复制标题
DOI：
10.1182/blood.v68.3.685.bloodjournal683685
复制
发表时间：
1986-09
期刊：
影响因子：
20.3
通讯作者：
Samuel;I. Rapaport;S. Paul;Bajaj
中科院分区：
文献类型：
--
作者：
Samuel;I. Rapaport;S. Paul;Bajaj
我们使用了激活肽释放试验来比较因子VII和激活因子VII （VIIa）的激活因子X、正常因子IX （IXN）和变异因子IX (IXBmLE)，后者在激活后无法反向激活因子VII。在纯化的系统中，因子VII和因子VIIa各自迅速激活因子X，但因子VII滞后一分钟。VIIa也很容易激活IXN和IXBmLE。因子VII最初未能激活大量的IXN或IXBmLE；在进一步的孵育过程中，因子VII激活了IXN而不是IXBmLE。当大约10%的因子VII转化为VIIa时，IXN开始激活，通过125i -因子VII放射性谱测量。在VIIa中加入因子VII可减缓其对IXBmLE的激活。然而，在因子X的存在下，仅因子VII就能快速激活IXBmLE。与纯化系统不同，1 nmol/L的VIIa添加到缺乏因子vii的血浆中未能激活因子IX。将因子VII增加到10 nmol/L（血浆浓度）作为天然的VII或VIIa，对因子IX和因子x产生相似的活化曲线。在因子x缺乏血浆和因子xii缺乏血浆中添加5%的VIIa大大缩短了稀释后的组织因子凝血时间。这些数据支持了因子VII/组织因子复合物通过最小生成Xa启动组织因子依赖性凝血的假设。然后，Xa迅速重新激活少量的因子VII，随后，因子IX和因子X的激活率急剧增加。
We have used activation peptide release assays to compare factor VII and activated factor VII (VIIa) activation of factor X, normal factor IX (IXN), and a variant factor IX (IXBmLE), which, after activation, is unable to back-activate factor VII. In purified systems, factor VII and VIIa each rapidly activated factor X, but after a one minute lag for factor VII. VIIa also readily activated both IXN and IXBmLE. Factor VII initially failed to activate substantial amounts of either IXN or IXBmLE; on further incubation factor VII activated IXN but not IXBmLE. Activation of IXN began when approximately 10% of factor VII had been converted to VIIa, as measured by 125I-factor VII radioactivity profiles. Adding factor VII to VIIa slowed its activation of IXBmLE. However, in the presence of factor X, factor VII alone rapidly activated IXBmLE. Unlike purified systems, 1 nmol/L VIIa added to factor VII-deficient plasma failed to activate factor IX. Increasing factor VII to 10 nmol/L (plasma concentration) either as native VII or VIIa yielded similar activation curves for factor IX and similar activation curves for factor X. Adding 5% VIIa to factor X-deficient plasma and to factor XII-deficient plasma substantially shortened the dilute tissue factor clotting time of only the former. These data support the hypothesis that factor VII/tissue factor complex initiates tissue factor-dependent clotting through a minimal generation of Xa. This Xa then rapidly back-activates a small amount of factor VII, following which the rates of activation of both factors IX and X increase dramatically.