What is the primary pathogenesis of Factor V Leiden (FVL) mutation?

The primary pathogenesis of Factor V Leiden (FVL) mutation is that it is refractory to proteolysis by activated protein C. Normally, activated protein C plays a crucial role in regulating blood clotting by inactivating coagulation factors, including Factor V. However, the FVL mutation results in a single amino acid substitution that makes Factor V resistant to this inactivation process.

Consequently, individuals with the FVL mutation have an increased risk of venous thromboembolism because their coagulation pathway remains excessively activated without the regulatory effect of activated protein C. This leads to an increased predisposition to thrombosis, as the normally tightly controlled clotting mechanisms become dysregulated.

Understanding this mechanism is critical because it highlights how a genetic mutation can lead to an increased risk of thrombotic events and informs both diagnosis and patient management for those affected. By recognizing the specific impact of the mutation on the proteolytic pathway, clinicians can better understand potential treatment options and preventive strategies for affected individuals.