Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid.
OBJECTIVE
We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA).


METHODS
DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h.


RESULTS
In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone.


CONCLUSIONS
Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH.
Department of Internal Medicine III, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, Ishikawa 920-8641, Japan. hasakura@med3.m.kanazawa-u.ac.jp
Hidesaku
H
Asakura
Yoko
Y
Sano
Tomotaka
T
Yoshida
Mika
M
Omote
Yasuo
Y
Ontachi
Tomoe
T
Mizutani
Masahide
M
Yamazaki
Eriko
E
Morishita
Akiyoshi
A
Takami
Ken-ichi
K
Miyamoto
Shinji
S
Nakao
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced* / Q000188:drug therapy; D004347:Drug Interactions; D005342:Fibrinolysis / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D023421:Models, Animal; D015849:Plasminogen Inactivators / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; D014148:Tranexamic Acid