Urinary protein C inhibitor as a therapeutic agent to disseminated intravascular coagulation (DIC): a comparison with low molecular weight heparin in rats with lipopolysaccharide-induced DIC.
We compared urinary protein C inhibitor (uPCI) with low molecular weight heparin (LMWH) in terms of the effect on the pathophysiology of disseminated intravascular coagulation (DIC), such as hypercoagulation, induction of secondary fibrinolysis and organ failure, using lipopolysaccharide (LPS)-induced DIC in rats. The uPCI (0.5 and 1.0 mg/kg) administration significantly inhibited both the decrease in fibrinogen level and the increase in fibrin/fibrinogen degradation products (FDP) level, and the effects compared favorably with those of LMWH (100 and 200 IU/kg). Both uPCI (0.5 and 1.0 mg/kg) and a low dose of LMWH also inhibited the increases in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), thrombin, and plasma kallikrein equally, but a high dose of LMWH did not inhibit the changes in those parameters. Furthermore, uPCI dose-dependently prevented the prolongation of activated partial thromboplastin time (APTT), while LMWH excessively prolonged APTT at a high dose. These results suggest that the preventive effect of uPCI on the pathophysiology of DIC compares favorably with that of LMWH, including the lack of a hemorrhagic reaction in contrast to LMWH.
Izutani
W
W
Development and Research Laboratories, JCR Pharmaceuticals Co., Ltd., Kobe, Japan.
Fujita
M
M
Nishizawa
K
K
Koga
J
J
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011486:Protein C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides; D011486:Protein C; D005340:Fibrinogen; D000410:Alanine Transaminase