Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates
Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates
复制标题
DOI：
10.1182/blood-2003-01-0324
复制
发表时间：
2003-08-01
期刊：
影响因子：
20.3
通讯作者：
Hanson, SR
中科院分区：
文献类型：
--
作者：
Gruber, A;Hanson, SR
通过激活因子 XI (FXI) 和/或组织因子 (TF)-因子 VIIa 产生的凝血酶对于血栓形成和止血至关重要。我们研究了在动脉血流条件下 FXI 依赖性血栓传播的作用，导致血栓快速生长，在起始阶段后，可能会限制血液/血栓界面处 TF 的可用性。通过将针织涤纶或呈 TF 的聚四氟乙烯移植物部署到经抗人 FXI 抗体 (aFXI) 处理的狒狒的动静脉分流器中，引发血栓形成。尽管aFXI不能阻止血栓形成，但它显着减少了管腔内血栓在两个表面上的生长。 aFXI 的抗血栓作用与肝素相当，剂量显着延长部分凝血活酶时间 (APTT)、凝血酶原时间 (PT) 和出血时间 (BT)。 aFXI 还延长了 APTT，但 PT 和 BT 不受影响。因此，与针对其他凝血因子的策略相比，FXI 的抗血栓靶向可能会抑制血栓形成，且止血损伤相对较轻。
Thrombin, generated through activation of factor XI (FXI) and/or tissue factor (TF)-factor VIIa, is essential for thrombosis and hemostasis. We investigated the role of FXI-dependent thrombus propagation under arterial flow conditions producing rapid thrombus growth that, after the initiation phase, could limit the availability of TF at the blood/thrombus interface. Thrombosis was initiated by knitted dacron or TF-presenting teflon grafts deployed into arteriovenous shunts in baboons treated with antihuman FXI antibody (aFXI). Although aFXI did not prevent thrombus initiation, it markedly reduced intraluminal thrombus growth on both surfaces. The antithrombotic effect of aFXI was comparable with that of heparin at doses that significantly prolonged the partial thromboplastin time (APTT), prothrombin time (PT), and bleeding time (BT). aFXI also prolonged the APTT, but the PT and BT were unaffected. Thus, antithrombotic targeting of FXI might inhibit thrombosis with relatively modest hemostatic impairment versus strategies targeting other coagulation factors.