title: Acquired deficiencies of protein S. Protein S activity during oral anticoagulation, in liver disease, and in disseminated intravascular coagulation.
abstract: Protein S is a vitamin K-dependent plasma protein which serves as the cofactor for activated protein C. Protein S circulates in both an active, free form and in an inactive complex with C4b-binding protein. To elucidate the role of protein S in disease states and during oral anticoagulation, we developed a functional assay for protein S that permits evaluation of the distribution of protein S between free and bound forms and permits determination of the specific activity of the free protein S. In liver disease, free protein S antigen is moderately reduced and the free protein S has significantly reduced specific activity. In disseminated intravascular coagulation, reduced protein S activity occurs due to a redistribution of protein S to the inactive bound form. During warfarin anticoagulation, reduction of free protein S antigen and the appearance of forms with abnormal electrophoretic mobility significantly decrease protein S activity. After the initiation of warfarin, the apparent half-life of protein S is 42.5 h. In patients with thromboembolic disease, transient protein S deficiency occurs due to redistribution to the complexed form. Caution should be exercised in diagnosing protein S deficiency in such patients by use of functional assays.
authors.affiliation: Cardiovascular/Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
authors.forename: A
authors.initials: A
authors.lastname: D'Angelo
authors.forename: S
authors.initials: S
authors.lastname: Vigano-D'Angelo
authors.forename: C T
authors.initials: CT
authors.lastname: Esmon
authors.forename: P C
authors.initials: PC
authors.lastname: Comp
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D004211:Disseminated Intravascular Coagulation / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007163:Immunosorbent Techniques; D008107:Liver Diseases / Q000378:metabolism*; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D011486:Protein C; D014859:Warfarin