The effect of factor Xa/phospholipid infusion on the acute phase response in baboons.
Disseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 +/- 0.23 g/l (mean +/- SE, n = 5; p < 0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 +/- 0.12 g/l). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 +/- 0.4 mg/l to a maximum of 33.0 +/- 7.3 at day one, which was five-fold higher (p < 0.01) than in control animals at day one (6.2 +/- 0.5 mg/l). Transient increases were observed within 6h for interleukin-6 from basal values of 6.2 +/- 1.7 ng/l to peak plasma levels of 42.9 +/- 21.4 ng/l, a value three-fold higher (p = 0.07) than in control animals (14.8 +/- 4.0 ng/l). The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.
Kruithof
E K
EK
Division of Angiology-Hemostasis, University Hospital, Geneva, Switzerland.
Agay
D
D
Mestries
J C
JC
Gascon
M P
MP
Ythier
A
A
D000210:Acute-Phase Reaction / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002417:Cattle; D004211:Disseminated Intravascular Coagulation / Q000097:blood*; D015951:Factor Xa / Q000008:administration & dosage / Q000633:toxicity*; D005340:Fibrinogen / Q000378:metabolism; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D010215:Papio; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D010718:Phosphatidylserines / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D013917:Thrombin / Q000096:biosynthesis
D015415:Biomarkers; D015850:Interleukin-6; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D005340:Fibrinogen; D002097:C-Reactive Protein; D013917:Thrombin; D015951:Factor Xa