Which clotting factors are inhibited by protein S?

Protein S serves as a crucial cofactor in the inactivation of clotting factors Va and VIIIa by activated protein C (APC). When activated protein C, with the help of protein S, acts on factor Va and factor VIIIa, it leads to their degradation, which diminishes thrombin generation and limits clot formation. This mechanism is essential for maintaining hemostatic balance and preventing excessive clotting, a condition that can lead to thrombosis.

While other factors, such as X, play a role in the clotting process, the specific inhibition by protein S pertains to factors Va and VIIIa, which are the active forms that facilitate the generation of thrombin. Understanding this interaction highlights the regulatory role of protein S in the coagulation cascade, illustrating its importance as a natural anticoagulant.