title: Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency.
abstract: Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans.
authors.affiliation: Service d'Hematologie-Immunologie, Hotel Dieu, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Conard
authors.forename: K A
authors.initials: KA
authors.lastname: Bauer
authors.forename: A
authors.initials: A
authors.lastname: Gruber
authors.forename: J H
authors.initials: JH
authors.lastname: Griffin
authors.forename: H P
authors.initials: HP
authors.lastname: Schwarz
authors.forename: M H
authors.initials: MH
authors.lastname: Horellou
authors.forename: M M
authors.initials: MM
authors.lastname: Samama
authors.forename: R D
authors.initials: RD
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000627:therapeutic use; D020151:Protein C Deficiency; D013927:Thrombosis / Q000209:etiology / Q000628:therapy
chemical_list: D011486:Protein C