Department of Gynecology, Ms.Clinic MayOne, Kashihara, Japan.
Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan.
J Obstet Gynaecol Res. 2023 Jul;49(7):1677-1683. doi: 10.1111/jog.15660. Epub 2023 Apr 25.
Tissue factor (TF), the primary initiator of the extrinsic coagulation pathway, contributes to the generation of a hypercoagulable and prothrombotic state in cancer patients. TF pathway inhibitor (TFPI) is a major inhibitor of TF-mediated coagulation pathway. The two proteins, TFPI1 and TFPI2, are encoded by separate genes. Indeed, various cancer patients with venous thromboembolism (VTE) had significantly lower TFPI1 levels than those without VTE. In contrast, serum TFPI2 level was found to increase in ovarian cancer patients with VTE. It remains unclear why TFPI2, unlike TFPI1, is elevated in ovarian cancer patients with VTE. The aim of this review is to explore the pathophysiological role of TFPI2 on the coagulation and fibrinolysis system.
A literature search was performed from inception to April 30, 2022 in the PubMed and Google Scholar databases.
TFPI1 and TFPI2 are homologs with different protease inhibitory activities in the coagulation and fibrinolysis system. TFPI1 inhibits TF/factor VIIa (FVIIa) catalyzed factor X (FX) activation. On the other hand, TFPI2 is unlikely to affect TF-initiated thrombin generation, but it has strong inhibitory activity against plasmin. Plasmin is involved in fibrin degradation, clot lysis, and inactivation of several coagulation factors (such as FV, FVIII, FIX, and FX). TFPI2 may increase the risk of VTE by inhibiting plasmin-dependent fibrinolysis.
TFPI1 and TFPI2 may have different key functions in regulating the coagulation and fibrinolytic systems.
组织因子（TF）是外源性凝血途径的主要启动子，它导致癌症患者处于高凝和血栓前状态。TF 途径抑制剂（TFPI）是 TF 介导的凝血途径的主要抑制剂。两种蛋白，TFPI1 和 TFPI2，分别由不同的基因编码。事实上，患有静脉血栓栓塞症（VTE）的各种癌症患者的 TFPI1 水平明显低于没有 VTE 的患者。相比之下，研究发现 VTE 的卵巢癌患者的血清 TFPI2 水平升高。目前尚不清楚为什么 TFPI2 与 TFPI1 不同，在 VTE 的卵巢癌患者中升高。本综述的目的是探讨 TFPI2 在凝血和纤溶系统中的病理生理作用。
从 2022 年 4 月 30 日起，在 PubMed 和 Google Scholar 数据库中进行了文献检索。
TFPI1 和 TFPI2 是凝血和纤溶系统中具有不同蛋白酶抑制活性的同源物。TFPI1 抑制 TF/FVIIa（FVIIa）催化的因子 X（FX）激活。另一方面，TFPI2 不太可能影响 TF 引发的凝血酶生成，但它对纤溶酶具有很强的抑制活性。纤溶酶参与纤维蛋白降解、血栓溶解和几种凝血因子（如 FV、FVIII、FIX 和 FX）的失活。TFPI2 通过抑制纤溶酶依赖性纤维蛋白溶解可能会增加 VTE 的风险。
TFPI1 和 TFPI2 可能在调节凝血和纤溶系统方面具有不同的关键功能。
