Clinical and genetic characterization of a protein S deficient patient with multiple thrombotic events

Abstract

Protein S (PS) is a plasma glycoprotein that plays an important role in the blood coagulation pathway. It functions as a cofactor for activated protein C (APC), aiding in the inactivation of certain coagulation factors. One of the main functions of PS is its role in facilitating the proximity of APC to the membrane surface and causing a repositioning of the active site, which accelerates the irreversible inactivation of activated factor V (FVa) and activated factor VIII (FVIIIa). 1,2 PS has also been found to act as a cofactor for the tissue factor inhibitor (TFPI). 3 In plasma, about 60% of PS protein is non-covalently bound to the complement component 4-binding protein β-chain (C4BP), and the remaining 40% is present in free form. PS deficiency can be categorized into three clinical subtypes based on the measurement of free and total PS antigen