Ragni M, Golino P, Cirillo P, Scognamiglio A, Piro O, Esposito N, Battaglia C, Botticella F, Ponticelli P, Ramunno L, Chiariello M
Department of Internal Medicine and Cardiovascular Sciences, University of Naples Federico II, Italy.
Circulation. 2000 Jul 4;102(1):113-7. doi: 10.1161/01.cir.102.1.113.
Tissue factor pathway inhibitor (TFPI) is the sole known inhibitor of the extrinsic coagulation pathway of physiological importance; however, its role in modulating thrombosis in vivo is still unclear.
Intravascular thrombosis was initiated by placing an external constrictor around endothelially injured rabbit carotid arteries (n=10). Carotid blood flow velocity was measured by a Doppler flow probe. After placement of the constrictor, cyclic flow reductions (CFRs), due to recurrent thrombosis, developed at the site of stenosis. Transstenotic TFPI plasma activity was measured in blood samples before induction of CFRs and after 30, 60, and 180 minutes of CFRs. TFPI plasma activity distal to the site of thrombosis was significantly lower than the corresponding proximal values at 30, 60, and 180 minutes of CFRs. In addition, a progressive decrease in TFPI plasma activity was observed in both the proximal and the distal samples, indicating consumption of TFPI during thrombus formation. In 10 additional rabbits, CFRs were abolished by administration of aspirin (10 mg/kg). In the animals in which aspirin abolished CFRs, endogenous TFPI was depleted by a bolus of a polyclonal antibody against rabbit TFPI, and the effects on restoration of CFRs were monitored. In 5 of 6 animals in which aspirin abolished CFRs, depletion of endogenous TFPI activity caused full restoration of CFRs.
The data of the present study support the involvement of endogenous TFPI in the process of thrombus formation in vivo and its active role in modulating arterial thrombosis.
组织因子途径抑制剂（TFPI）是已知唯一对生理凝血外源性途径具有重要抑制作用的物质；然而，其在体内调节血栓形成中的作用仍不明确。
通过在兔内皮损伤的颈动脉周围放置外部收缩器（n = 10）引发血管内血栓形成。用多普勒血流探头测量颈动脉血流速度。放置收缩器后，狭窄部位出现因反复血栓形成导致的周期性血流减少（CFRs）。在诱导CFRs之前以及CFRs出现30、60和180分钟后，对血样中的跨狭窄TFPI血浆活性进行测量。在CFRs出现30、60和180分钟时，血栓形成部位远端的TFPI血浆活性显著低于相应的近端值。此外，在近端和远端样本中均观察到TFPI血浆活性逐渐下降，表明在血栓形成过程中TFPI被消耗。在另外10只兔子中，通过给予阿司匹林（10mg/kg）消除了CFRs。在阿司匹林消除CFRs的动物中，通过注射抗兔TFPI多克隆抗体耗尽内源性TFPI，并监测其对CFRs恢复的影响。在6只阿司匹林消除CFRs的动物中，有5只内源性TFPI活性的耗尽导致CFRs完全恢复。
本研究数据支持内源性TFPI参与体内血栓形成过程及其在调节动脉血栓形成中的积极作用。
