Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency.
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.
Conard
J
J
Service d'Hematologie-Immunologie, Hotel Dieu, Paris, France.
Bauer
K A
KA
Gruber
A
A
Griffin
J H
JH
Schwarz
H P
HP
Horellou
M H
MH
Samama
M M
MM
Rosenberg
R D
RD
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
D011486:Protein C