Activated Factor VII-Antithrombin Complex, a Biomarker of Tissue Factor-Related Pathways in Different Clinical Settings: A Narrative Review from Cardiovascular Diseases to Cancer

Tissue factor (TF) is a transmembrane glycoprotein that represents the fundamental physiological initiator of the coagulation cascade through its interaction with factor VII. TF belongs to the cytokine receptor protein superfamily and contributes to the transduction of cellular signaling. Therefore, TF-related pathways are involved in multiple pathophysiological processes, not only in coagulation/thrombosis but in a wider mechanisms' panorama, ranging from infective to neoplastic diseases. Consistently, the measurement of TF activity could have a diagnostic and/or prognostic meaning in different clinical conditions. However, the transmembrane localization, the expression on different cellular types and circulating extracellular vesicles, and the different conformations (encrypted and decrypted) and variants (such as the soluble alternatively spliced TF) hamper TF assessment in clinical practice. The activated factor VII-antithrombin (FVIIa-AT) complex is proposed as an indirect biomarker of the TF-FVIIa interaction and, consequently, of the functionally active TF expression. In this narrative review, we evaluate the clinical studies investigating the role of plasma concentration of FVIIa-AT in health and disease. Although without conclusive data, high FVIIa-AT concentrations predict the worst clinical outcomes in different pathologic conditions, such as cardiovascular disease and cancer, thereby suggesting that overactivation of TF-related pathways may play an unfavorable role in various clinical settings.