Physiological concentrations of tissue factor pathway inhibitor do not inhibit prothrombinase.
Physiological concentrations of tissue factor pathway inhibitor do not inhibit prothrombinase.
复制标题
DOI：
10.1182/blood.v87.5.1845.bloodjournal8751845
复制
发表时间：
1996-03
期刊：
影响因子：
20.3
通讯作者：
AE Mast;G. Broze
中科院分区：
文献类型：
--
作者：
AE Mast;G. Broze
组织因子途径抑制剂（TFPI）是一种Kunitz型丝氨酸蛋白酶抑制剂，可直接抑制因子Xa，并以因子Xa依赖性方式抑制因子VIIa/组织因子催化复合物。使用凝血酶原酶复合物的纯化组分检查TFPI在凝血酶原活化测定中的抑制作用。当Xa因子加入到含有TFPI、凝血酶原、钙离子和非活化血小板或因子V和磷脂的混合物中时，TFPI显著降低随后的凝血酶生成，并且肝素增强了抑制作用。如果在加入凝血酶原和生理浓度的TFPI（< 8 nmol/L）之前，将因子Xa与钙离子和凝血酶活化的血小板或因子Va和磷脂预孵育以形成凝血酶原酶，则即使在肝素存在下，也会发生对凝血酶生成的最小抑制。因此，与用显色底物的酰胺分解试验的结果相反，凝血酶原酶在其生理底物凝血酶原存在下对TFPI的抑制具有抗性。较高浓度的TFPI（约100 nmol/L），类似于在动物研究中用于测试TFPI治疗作用的那些，确实有效地阻断凝血酶原酶活性。
Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine proteinase inhibitor that directly inhibits factor Xa and, in a factor Xa dependent manner, inhibits the factor VIIa/tissue factor catalytic complex. The inhibitory effect of TFPI in prothrombin activation assays using purified components of the prothrombinase complex was examined. When factor Xa is added to mixtures containing TFPI, prothrombin, calcium ions, and nonactivated platelets or factor V and phospholipids, TFPI significantly reduces subsequent thrombin generation, and the inhibitory effect is enhanced by heparin. If factor Xa is preincubated with calcium ions and thrombin-activated platelets or factor Va and phospholipids to permit formation of prothrombinase before the addition of prothrombin and physiologic concentrations of TFPI (< 8 nmol/L), minimal inhibition of thrombin generation occurs, even in the presence of heparin. Thus, contrary to results in amidolytic assays with chromogenic substrates, prothrombinase is resistant to inhibition by TFPI in the presence of its physiological substrate, prothrombin. Higher concentrations of TFPI (approximately 100 nmol/L), similar to those used in animal studies testing for therapeutic actions of TFPI, do effectively block prothrombinase activity.