Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis.
Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis.
复制标题
血浆中凝血酶对因子 XI 的反馈激活导致凝血酶的额外形成，从而保护纤维蛋白凝块免于纤维蛋白溶解。
作者：
Peter;Kr. von dern Borne;C. M. Meijers;Bonno;Bourna
最近，一个替代途径的因子XI活化已被描述，其中因子XI是由凝血酶激活。因子XI缺乏症患者出血多来自局部纤溶活性高的组织。因此，在血浆系统中研究了凝血酶介导的因子XI激活在纤维蛋白形成和纤维蛋白溶解中的作用。在存在或不存在组织型纤溶酶原激活剂的情况下，将组织因子或凝血酶添加到再钙化血浆中诱导凝血，之后使用浊度法测量凝块形成和溶解。在缺乏葡聚糖硫酸盐样辅助因子的生理条件下，凝血酶介导的因子XI激活在血浆中发生。在高组织因子浓度下，未观察到因子XI对纤维蛋白形成速率的影响。组织因子的减少导致因子XI对纤维蛋白形成速率的贡献逐渐增加。此外，凝血酶介导的因子XI激活导致组织型纤溶酶原激活物诱导的凝块溶解受到抑制。这种抑制甚至发生在组织因子浓度下，在没有观察到因子XI对纤维蛋白形成的影响。微量的活化因子XI （1.25 pmol/L，代表0.01%的活化）能够完全抑制我们系统中的纤维蛋白溶解。抑制作用被发现是由凝血酶介导的，凝血酶是通过内在途径以因子xi依赖的方式产生的，并且能够保护凝块免受溶解。我们还观察到，在凝块形成后，额外凝血酶的形成仍在继续。我们得出结论，凝血酶介导的因子XI激活可以在血浆中发生。在凝血过程中，因子XI的存在导致在凝块内形成额外的凝血酶，能够保护该凝块免受纤溶性攻击。大量凝血酶通过内在途径通过因子XI形成，可能在凝块的促凝和血栓形成状态中发挥重要作用，因此可能具有重要的临床和治疗意义。
Recently, an alternative pathway for factor XI activation has been described in which factor XI is activated by thrombin. Patients with a factor XI deficiency bleed mostly from tissues with high local fibrinolytic activity. Therefore, the role of thrombin-mediated factor XI activation in both fibrin formation and fibrinolysis was studied in a plasma system. Clotting was induced by the addition of tissue factor or thrombin to recalcified plasma in the presence or absence of tissue-type plasminogen activator, after which clot formation and lysis were measured using turbidimetry. Thrombin-mediated activation of factor XI was found to take place in plasma under physiologic conditions in the absence of a dextran sulfate-like cofactor. At high tissue factor concentrations, no effect of factor XI was seen on the rate of fibrin formation. Decreasing amounts of tissue factor resulted in a gradually increasing contribution of factor XI to the rate of fibrin formation. In addition, thrombin-mediated factor XI activation resulted in an inhibition of tissue-type plasminogen activator-induced lysis of the clot. This inhibition occurred even at tissue factor concentrations at which no effect of factor XI was observed on fibrin formation. Trace amounts of activated factor XI (1.25 pmol/L, representing 0.01% activation) were capable of completely inhibiting fibrinolysis in our system. The inhibitory effect was found to be mediated by thrombin that is additionally generated in a factor XI-dependent manner via the intrinsic pathway and is capable of protecting the clot against lysis. We also observed that formation of additional thrombin continued after the clot had been formed. We conclude that thrombin-mediated factor XI activation can take place in plasma. The presence of factor XI during coagulation results in the formation of additional thrombin within the clot capable of protecting this clot from fibrinolytic attack. The large amounts of thrombin that are formed by the intrinsic pathway via factor XI may play an important role in the procoagulant and thrombogenic state of clots and may therefore have important clinical and therapeutic implications.
登录
查看更多内容
影响因子：
20.3
作者：
D. Gailani;G. Broze
通讯作者：
D. Gailani;G. Broze
因子 IX 和因子 IXa 与人血小板的相互作用的比较。
DOI：
--
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ahmad,SS;Rawala-Sheikh,R;Walsh,PN
通讯作者：
Walsh,PN
影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
影响因子：
20.3
作者：
A. Gruber;E. Mori;G. D. del Zoppo;L. Waxman;J. Griffin
通讯作者：
A. Gruber;E. Mori;G. D. del Zoppo;L. Waxman;J. Griffin
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lawson,JH;Kalafatis,M;Stram,S;Mann,KG
通讯作者：
Mann,KG