title: An update on clinical and basic aspects of the protein C anticoagulant pathway.
abstract: The protein C anticoagulant pathway provides a mechanism for regulating the coagulation process through the selective inactivation of factors Va and VIIIa. Recent studies have suggested that factor V may facilitate this process and that a mutation at one of the inactivation sites can contribute to resistance to activated protein C (APC) inactivation of factor Va. This appears to be a common cause of familial thrombophilia. The control mechanisms involved in factor Va inactivation have also begun to become more clear. Membrane surfaces seem to be critical to complete factor Va inactivation, and the membrane composition requirements for optimal anticoagulant activity are distinct from those of procoagulant reactions. Specifically, the APC anticoagulant activity requires phosphatidylethanolamine, whereas the prothrombin activation complex does not. These observations may partially explain thrombotic complications with antiphospholipid antibodies in which the some antibodies have been shown to react preferentially with phosphatidylethanolamine and could, therefore, selectively block APC function. Clinically, more complete studies on partial protein C deficiency indicate that, at least within families, the deficiency is a significant risk factor for thrombosis. The impact of deficiencies on thrombotic risk suggests that protein C or other components of the pathway may be useful therapeutic agents. The limited clinical experience in treating meningococcemia, warfarin-induced skin necrosis, and homozygous protein C deficiency with protein C concentrates suggests that this approach is safe and effective.
authors.affiliation: Charles Esmon is at the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; the Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; the Howard Hughes Medical Institute, Oklahoma City, OK 73104, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Esmon
authors.forename: H P
authors.initials: HP
authors.lastname: Schwarz