Effects of low molecular weight heparin, alone or combined with antithrombin III, on mortality, fibrin deposits and hemostatic parameters in endotoxin-induced disseminated intravascular coagulation in rabbits

The effect of low molecular weight heparin (LMWH) with or without antithrom bin III (AT III) has been studied in a rabbit model of disseminated intrava scular coagulation (DIC) induced by continuous infusion of 100 mu g/kg/hr o f Escherichia coli endotoxin for 6 hr. LMWH (5 and 10 IU/kg/hr/6 hr), alone or in combination with AT III (20 U/kg/hr/6 hr), or saline were administer ed simultaneously with endotoxin. Hemostatic markers at 0, 2, and 6 hr as w ell as kidney fibrin deposits and the mortality rate at 24 hr were determin ed. Rabbits receiving only endotoxin showed an impairment in hemostasis, as well as high kidney fibrin deposits and a high mortality rate. LMWH alone did not exert any effect. The simultaneous infusion of LMWH and AT III exer ted a beneficial effect on the hemostatic markers and reduced the kidney fi brin deposits as well as the mortality rate in a LMWH dose-dependent manner . Fibrinogen and protein C consumption were significantly higher and renal fibrin deposits more intense in the rabbits that had died in the first 24 h r. There was also a significant positive correlation between kidney fibrin deposits and platelets, fibrinogen, and protein C consumption, taking the w hole rabbit population. It is concluded that the simultaneous infusion of L MWH and AT III is useful in this DIC model and would make it possible to re duce significantly the AT III doses used when AT III is given alone. (C) 19 99 Wiley-Liss, Inc.