Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model.
The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, without the severe side effects associated with bacterial sepsis. Quantitative determination of canine plasma protein C levels were performed using a multiple step amidolytic assay, that included a specific precipitation of the vitamin K-dependent proteins from citrated plasma, followed by thrombin activation (and neutralization) and subsequent measurement of the activated protein C (APC) by chromogen hydrolysis. This investigation demonstrated, that over a twenty-four hour interval, intradermal administration of endotoxin produces a gradual decrease in the PC activity levels, concomitant with a significant reduction in the Factor V, Factor VIII and fibrinogen levels and platelet count, and a prolongation of the Prothrombin Time and Partial Thromboplastin Time. During the first 6 hours, protein C levels fell below the pre-levels and remained significantly lower in the surviving dogs. Thus, this endotoxin-induced DIC animal model permits evaluation of various hemostatic parameters, yet diminishes the severe clinical findings associated with DIC.
Laboratory Service, Veterans Administration Medical Center, Denver, CO.
R M
RM
Madden
M
M
Ward
R A
RA
Marlar
D000818:Animals; D001779:Blood Coagulation Factors / Q000032:analysis; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000139:chemically induced; D004285:Dogs; D004731:Endotoxins / Q000008:administration & dosage* / Q000097:blood; D006403:Hematologic Tests; D008297:Male; D011486:Protein C / Q000378:metabolism*
D001779:Blood Coagulation Factors; D004731:Endotoxins; D011486:Protein C