The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.
The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.
复制标题
重组VIIa因子在体内对X因子和凝血酶原的激活是由组织因子介导的。
DOI：
10.1172/jci116691
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Rosenberg,RD
中科院分区：
文献类型：
--
作者：
tenCate,H;Bauer,KA;Levi,M;Edgington,TS;Sublett,RD;Barzegar,S;Kass,BL;Rosenberg,RD
人凝血系统持续产生非常少量的Xa因子和凝血酶。目前的证据表明，止血机制的基础水平激活是通过viia依赖性因子X的激活发生的，但没有直接证据表明组织因子参与了这一途径。为了研究这一问题，我们向正常黑猩猩注射了相对高浓度的重组VIIa因子（约50微克/千克体重），并观察到因子IX激活肽、因子X激活肽和凝血酶原激活片段F1+2的血浆水平显著增加。用放射性标记的因子IX激活肽、因子X激活肽和F1+2进行代谢转换研究表明，激活肽水平升高是由于三种凝血系统酶原加速转化为丝氨酸蛋白酶。给药组织因子强效单克隆抗体，可立即在体外中和VIIa-组织因子复合物的功能，消除重组蛋白介导的因子X和凝血酶原的活化，并抑制基础水平的因子IX和因子X的活化。上述结果表明，重组因子VIIa通过与内源性组织因子位点相互作用而发挥止血前药物的作用。但明确的证据需要在血友病动物中使用相关的止血终点进行研究。
The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrations of recombinant Factor VIIa (approximately 50 micrograms/kg body wt) into normal chimpanzees and observed significant increases in the plasma levels of Factor IX activation peptide, Factor X activation peptide, and prothrombin activation fragment F1+2. Metabolic turnover studies with radiolabeled Factor IX activation peptide, Factor X activation peptide, and F1+2 indicate that elevated levels of the activation peptides are due to accelerated conversion of the three coagulation system zymogens into serine proteases. The administration of a potent monoclonal antibody to tissue factor, which immediately neutralizes function of the Factor VIIa-tissue factor complex in vitro, abolishes the activation of Factor X and prothrombin mediated by the infused recombinant protein, and also suppresses basal level activation of Factor IX and Factor X. The above results suggest that recombinant Factor VIIa functions as a prohemostatic agent by interacting with endogenous tissue factor sites, but definitive proof will require studies in hemophilic animals using relevant hemostatic endpoints.