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 antithrombin III (AT III) has been studied in a rabbit model of disseminated intravascular coagulation (DIC) induced by continuous infusion of 100 microg/kg/hr of 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 administered simultaneously with endotoxin. Hemostatic markers at 0, 2, and 6 hr as well as kidney fibrin deposits and the mortality rate at 24 hr were determined. 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 exerted a beneficial effect on the hemostatic markers and reduced the kidney fibrin 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 hr. There was also a significant positive correlation between kidney fibrin deposits and platelets, fibrinogen, and protein C consumption, taking the whole rabbit population. It is concluded that the simultaneous infusion of LMWH and AT III is useful in this DIC model and would make it possible to reduce significantly the AT III doses used when AT III is given alone.
Hermida
J
J
Laboratory of Vascular Biology and Thrombosis, School of Medicine, University of Navarra, Pamplona, Spain.
Montes
R
R
Muñoz
M C
MC
Orbe
J
J
Páramo
J A
JA
Rocha
E
E
D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000187:drug effects*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000401:mortality*; D004338:Drug Combinations; D004731:Endotoxins; D005337:Fibrin / Q000187:drug effects / Q000378:metabolism*; D005340:Fibrinogen / Q000032:analysis; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D006652:Histological Techniques; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D010976:Platelet Count; D011486:Protein C / Q000032:analysis; D011817:Rabbits
D001779:Blood Coagulation Factors; D004338:Drug Combinations; D004731:Endotoxins; D006495:Heparin, Low-Molecular-Weight; D011486:Protein C; D000990:Antithrombin III; D005337:Fibrin; D005340:Fibrinogen