Treatment effects of recombinant human soluble thrombomodulin in patients with septic urinary tract infection-induced disseminated intravascular coagulation

Y. Hashimoto, K. Tozawa, K. Kohri
2014 International Journal of Infectious Diseases  
Urinary tract infection (UTI) complicates sepsis and/or disseminated intravascular coagulation (DIC) when the disease becomes severe; mortalities of septic DIC is reported to reach to 37% despite current therapy. Cross-talk between the coagulation system and inflammatory reactions during sepsis causes organ damage followed by multiple organ dysfunction syndrome or even death. Therefore, anticoagulant therapies have been expected to be beneficial in the treatment of severe sepsis. Recombinant
more » ... an soluble thrombomodulin (rhTM) binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce activated protein C. The purpose of this study was to examine the efficacy of rhTM for treating patients with septic UTIinduced DIC. Methods & Materials: This study comprised 45 patients with septic UTI-induced DIC. All patients fulfilled the criteria of severe sepsis and the International Society on Thrombosis and Haemostasis criteria for overt DIC. The initial 25 patients were treated without rhTM (control group), and the following 20 consecutive patients were treated with rhTM (0.06 mg/kg/day) for six days (rhTM group). The primary outcome measure was 28-day mortality. Stepwise multivariate Cox regression analysis was used to assess which independent variables were associated with mortality. Comparisons of Sequential Organ Failure Assessment (SOFA) score on sequential days between the two groups were analyzed by repeated measures analysis of variance. Results: Cox regression analysis showed 28-day mortality to be significantly lower in the rhTM group than in the control group (adjusted hazard ratio, 0.301; 95% confidence interval, 0.104 to 0.867; P = 0.028). SOFA score in the rhTM group decreased significantly in comparison with that in the control group (P = 0.029). In the post hoc test, SOFA score decreased rapidly in the rhTM group compared with that in the control group on day 1 (P < 0.05). Conclusion: We found that rhTM administration may improve organ dysfunction in patients with septic UTI-induced DIC. Further clinical investigations are necessary to evaluate the effect of rhTM on the pathophysiology of septic UTI-induced DIC. http://dx.
doi:10.1016/j.ijid.2014.03.877 fatcat:vb2tt67qtvfnzg4e3n2yf3dwiq