Consumption of plasma factor VII in a rabbit model of non-overt disseminated intravascular coagulation.
BACKGROUND
We have recently described an experimental animal model of non-overt disseminated intravascular coagulation (DIC) in the rabbit in which the induction of tissue factor (TF) mRNA and TF antigen expression in peripheral blood leukocytes (PBL) was demonstrated to occur within 2 h of administration of low-dose endotoxin [Hematol. J. 2 (2001) 188]. In the present study, we demonstrate that the leukocyte TF expressed has procoagulant activity leading to a rapid decline in the concentration of factor VII (FVII) in rabbit plasma.


METHODS
Total plasma FVII antigen and FVIIa were quantitated by rabbit FVII-specific immunoassay and FVIIa-specific clotting assays, respectively. Plasma samples from either saline-injected rabbits or rabbits administered a single bolus of 10 microg/kg Salmonella lipopolysaccharide were compared over a 24-h period.


RESULTS
Total plasma FVII antigen decreased progressively post-endotoxin injection, reaching 71% of the baseline concentration at 8 h (p<0.001, n=18), and remained low (78%) at 24 h post-injection (p<0.01, n=16), returning to normal by 48 h. Plasma FVIIa levels increased to 120% within 2 h of endotoxin injection, fell to 73% of the baseline concentration at 8 h (p<0.05, n=18) and returned to normal by 24 h post-endotoxin administration. Procoagulant activity of rabbit peripheral blood leukocytes was enhanced at 2 h (p<0.01, n=6) and 4 h (p<0.05, n=6) post-endotoxin injection. The prothrombin time (PT) was increased by <3 s, and thrombin-antithrombin (TAT) complex formation was not significantly increased in the plasma of endotoxin-treated rabbits. No significant changes in total plasma FVII antigen, FVIIa or leukocyte procoagulant activity were observed in rabbits treated with saline.


CONCLUSIONS
We conclude that the activation of FVII to FVIIa and rapid consumption of total FVII/FVIIa occur very early and likely are integral events linked to the initiation and propagation of non-overt DIC induced by endotoxin.
Clarke
Bryan J
BJ
Department of Pathology and Molecular Medicine, HSC 4N65, McMaster University, 1200 Main St. West, L8N 3Z5, Hamilton, Ontario, Canada. bjclarke@mcmaster.ca
Sridhara
Sampath
S
Woskowska
Zofia
Z
Blajchman
Morris A
MA
D000818:Animals; D000990:Antithrombin III; D001777:Blood Coagulation; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood*; D004731:Endotoxins / Q000494:pharmacology; D005167:Factor VII / Q000378:metabolism*; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood; D011517:Prothrombin Time; D011817:Rabbits
D004731:Endotoxins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005167:Factor VII; D010447:Peptide Hydrolases