Mackman Nigel, Sachetto Ana T A
Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Blood Vessel Thromb Hemost. 2024 Jul 31;1(4):100022. doi: 10.1016/j.bvth.2024.100022. eCollection 2024 Dec.
Tissue factor (TF) is a transmembrane protein that, in association with its ligand factor VII (FVII)/activated factor VII (FVIIa), activates blood coagulation. TF is highly procoagulant and even very small amounts can activate blood coagulation. Levels of TF-positive extracellular vesicles (EVs) are increased in blood in diseases associated with thrombosis. However, it is challenging to accurately quantify the very low levels of TF in blood. Activity-based assays have higher sensitivity and specificity than antigen-based assays. Many anti-human TF antibodies have been generated but they differ in their affinity for TF and bind to different epitopes. They can be divided into 2 groups: those that compete with FVII/FVIIa binding to TF, and those that bind to both TF and the TF-FVII/VIIa complex. Commercial enzyme-linked immunosorbent assays are commonly used to measure TF antigen in plasma but have low sensitivity and specificity for the detection of TF antigen in plasma. Flow cytometry is used to measure TF antigen on EVs but also has low sensitivity and specificity. Functional TF activity assays should be performed in the presence and absence of an inhibitory anti-TF antibody to distinguish between TF-dependent and TF-independent FXa generation because FVIIa can activate FX in the absence of TF. TF pathway inhibitor inhibits the TF-FVIIa complex and reduces TF activity of isolated EVs. Two commercial assays are available for the measurement of TF activity of EVs isolated from human plasma. Measurement of TF activity of EVs isolated from plasma may be a useful biomarker of thrombotic risk in different diseases.
组织因子（TF）是一种跨膜蛋白，它与配体因子VII（FVII）/活化因子VII（FVIIa）结合后可激活血液凝固。TF具有高度促凝性，即使极少量也能激活血液凝固。在与血栓形成相关的疾病中，血液中TF阳性细胞外囊泡（EVs）的水平会升高。然而，准确量化血液中极低水平的TF具有挑战性。基于活性的检测方法比基于抗原的检测方法具有更高的灵敏度和特异性。已经产生了许多抗人TF抗体，但它们对TF的亲和力不同，且结合不同的表位。它们可分为两组：与FVII/FVIIa竞争结合TF的抗体，以及既能结合TF又能结合TF-FVII/VIIa复合物的抗体。商业酶联免疫吸附测定通常用于测量血浆中的TF抗原，但对血浆中TF抗原的检测灵敏度和特异性较低。流式细胞术用于测量EVs上的TF抗原，但灵敏度和特异性也较低。应在存在和不存在抑制性抗TF抗体的情况下进行功能性TF活性测定，以区分TF依赖性和TF非依赖性FXa的产生，因为FVIIa在没有TF的情况下也能激活FX。TF途径抑制剂可抑制TF-FVIIa复合物并降低分离的EVs的TF活性。有两种商业检测方法可用于测量从人血浆中分离的EVs的TF活性。测量从血浆中分离的EVs的TF活性可能是不同疾病中血栓形成风险的有用生物标志物。
