# Factor VII-Activating Protease (FSAP) and Its Importance in Hemostasis—Part II: A Link Between FSAP, Blood Coagulation, and Fibrinolysis: A Narrative Review

## TL;DR

This review explores how factor VII-activating protease (FSAP) influences blood clotting and clot breakdown, highlighting its role in modulating coagulation and fibrinolysis.

## Contribution

The paper provides a narrative synthesis of FSAP's dual roles in coagulation and fibrinolysis, emphasizing its context-dependent effects and key research gaps.

## Key findings

- FSAP enhances thrombin generation mainly by inactivating TFPI, with limited direct activation of FVII.
- FSAP indirectly accelerates clot lysis by converting scuPA to tcuPA and modifying fibrinogen chains.
- FSAP modulates clot architecture, increasing susceptibility to proteolysis through altered fiber structure.

## Abstract

As a continuation of Part I on the structure and regulation of factor VII-activating protease (FSAP), this narrative review synthesizes mechanistic, translational, and limited clinical evidence to delineate FSAP’s roles at the interface of coagulation and fibrinolysis. Current evidence indicates that FSAP enhances thrombin generation primarily via proteolytic inactivation of tissue factor pathway inhibitor (TFPI), whereas direct activation of factor VII (FVII) by FSAP appears weak or context-restricted. Beyond plasma proteins, FSAP can upregulate tissue factor (TF) in human macrophages, while platelet-related effects remain insufficiently substantiated. On the fibrinolytic axis, FSAP indirectly accelerates clot lysis by converting single-chain urokinase (scuPA) to its active two-chain form (tcuPA) and, less efficiently, by processing tissue-type plasminogen activator (tPA); in addition, selective cleavage of fibrinogen Aα and Bβ chains remodels clot architecture, yielding thinner fibers with higher density and increased susceptibility to proteolysis. Collectively, the data position FSAP as a context-sensitive modulator of thrombin generation and fibrin turnover. Key gaps include isoform specificity, in vivo cellular targets, and the quantitative contribution of the FSAP-TFPI and FSAP–fibrinogen–urokinase/tPA axes in human pathophysiology, which warrant focused mechanistic and clinical studies.