Low molecular weight heparin attenuates multiple organ failure in a murine model of disseminated intravascular coagulation.
OBJECTIVE
Bacterial sepsis causes widespread vascular inflammation that frequently leads to disseminated intravascular coagulation (DIC). Although intravascular coagulation contributes to organ failure, it is often debated whether anticoagulant therapy produces any beneficial effects in patients with DIC. The aim of this study was to document potential beneficial effects of low molecular weight heparin (LMWH) in a lipopolysaccharide-induced DIC model.


METHODS
Controlled animal experiment combined with an in vitro laboratory study.


METHODS
Academic research laboratory.


METHODS
C57BL/6 mice subjected to two injections of Serratia Marcescens lipopolysaccharide (LPS) resulting in the generalized Shwartzman's reaction as a model for DIC.


METHODS
LMWH (5 IU of anti-Xa activity) or saline was administered before both LPS injections and 10 hrs after the first exposure to LPS. To test the effect of LMWH on LPS-driven monocyte inflammatory responses, a human monocyte-human umbilical vein endothelial cell co-culture was used to determine E-selectin expression as a marker of monocyte adherence.


RESULTS
In our murine DIC model, LMWH had no effect on markers of inflammation. In addition, no effect of LMWH was detected on monocyte adherence in the human monocyte-human umbilical vein endothelial cell co-culture. Organ damage, contrarily, was significantly reduced as determined by hepatic necrosis (p < .05), lung epithelial protein leakage (p < .05), and creatinine release from kidneys into plasma (p < .01). LMWH protection from organ failure resulted in an increase in survival (p = .06) in this model for DIC.


CONCLUSIONS
These results demonstrate the significance of blood coagulation in the progression of DIC and hint at a beneficial role for LMWH anticoagulation in the management of DIC.
Slofstra
Sjoukje H
SH
Laboratory for Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van 't Veer
Cornelis
C
Buurman
Wim A
WA
Reitsma
Pieter H
PH
ten Cate
Hugo
H
Spek
C Arnold
CA
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000401:mortality; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects; D009102:Multiple Organ Failure / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides