Les déficits congénitaux en protéine S ; difficultés diagnostiques

Abstract

Protein S is a physiologic inhibitor of coagulation acting as a cofactor of activated protein C (APC) that inhibits factor Va and VIII. Approximately 60% of PS is bound to C4bBP, a protein of the complement system and only the free PS has a cofactor PCa role. Congenital PS deficiencies are diagnosed by immunologic dosage of free and total PS and functional assay evaluating APC cofactor activity. However, it has been demonstrated a direct anticoagulant activity of free PS, non-dependant of APC on the cascade coagulation and even PS bound to C4bBP seems to have anticoagulant properties. So, it appears that functional assays available estimate only a part of PS anticoagulant activities and, in addition, many interferences are reported with these tests (lupus anticoagulant, factor V Leiden, factor VIII excess…). Immunologic dosages are more reliable in spite of rare qualitative PS deficiencies that could be non-diagnosed. PS deficiencies are often difficult to diagnose because of an overlapping between normal and pathological values. Familial studies are necessary to prove the hereditary origin because there are several causes of acquired and sometimes persistent PS deficiencies (liver insufficiency, vitamin K absence, hormonal therapy in women, PS auto immune deficiency). About 200 different mutations were retrieved and, therefore, molecular studies are not of current practice. It is recommended currently to measure in first intention the free PS, if possible in association with PCa cofactor activity.