title: Oral anticoagulation reduces activated protein C less than protein C and other vitamin K-dependent clotting factors.
abstract: Oral anticoagulant therapy, which is used for prophylaxis and management of thrombotic disorders, causes similar reductions in plasma levels of vitamin K-dependent procoagulant and anticoagulant clotting factor zymogens. When we measured levels of circulating activated protein C, a physiologically important anticoagulant and anti-inflammatory agent, in patients on oral anticoagulant therapy, the results unexpectedly showed that such therapy decreases levels of activated protein C substantially less than levels of protein C, prothrombin, and factor X, especially at lower levels of prothrombin and factor X. Thus, we suggest that oral anticoagulant therapy results in a relatively increased expression of the protein C pathway compared with procoagulant pathways not only because there is less prothrombin to inhibit activated protein C anticoagulant activity, but also because there is a disproportionately higher level of circulating activated protein C.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Haematology, and Department of Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands. m.simmelink@lab.azu.nl
authors.forename: Marleen J A
authors.initials: MJ
authors.lastname: Simmelink
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Ronald H W M
authors.initials: RH
authors.lastname: Derksen
authors.forename: José A
authors.initials: JA
authors.lastname: Fernandez
authors.forename: John H
authors.initials: JH
authors.lastname: Griffin
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000187:drug effects*; D005170:Factor X / Q000187:drug effects; D006331:Heart Diseases / Q000097:blood; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D011486:Protein C / Q000187:drug effects*; D011516:Prothrombin / Q000187:drug effects; D014812:Vitamin K
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011486:Protein C; D014812:Vitamin K; D011516:Prothrombin; D005170:Factor X