THE EFFECT OF FACTOR XA PHOSPHOLIPID INFUSION ON THE ACUTE-PHASE RESPONSE IN BABOONS/

Disseminated intravascular coagulation (DIG) is a frequent compli cati on of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not k nown whether thrombin or fibrin deposition may directly induce an acut e 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 fib rinogen and a high dosage (two injections at 5h interval; 3 animals) l eading to complete fibrinogen depletion: Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 +/- 0.2 3 g/l (mean +/- SE, n = 5; p < 0.01 with respect to basal levels) at d ay 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were obser ved (maximal values: 1.88 +/- 0.12 gill. Serum concentrations of C-rea ctive 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). Trans ient increases were observed within 6 h for interleukin-6 from basal v alues of 6.2 +/- 1.7 ng/l to peak plasma levels of 42.9 +/- 21.4 ng/l, a value threefold higher (p = 0.07) than in control animals (14.8 +/- 4.0 ng/l). The preliminary results of this observational study sugges t that factor Xa/phospholipid infusion is followed by an acute phase r esponse, leading after one day to significant increases of fibrinogen and of C-reactive protein.