Treatment effects of Antithrombine,recombinant human soluble thrombomoduline(ART-123) and heparin on disseminated intravascular coagulation(DIC) in patients withsepsis:a systematic review of Randomized control trials

Background and objectives To review the efficacy of antithrombin(AT),recombinant human soluble thrombomoduline(ART-123) and heparin on DIC in patients with sepsis with a comparison-based review. Methods A systematic review of all randomized controlled trials (RCTs) that examined the impact of AT,ART-123,heparin on DIC-recovery,reduction in mortality rate and adverse events such as major bleeding. Databases such as MEDLINE and Cochrane library were searched up to November 2016. Trials were included if they compared effects of interventions with a control group. trials were limited to English language studies with accessible free full text. 4 studies had adequate blinding statistics. Included studies had checked with The Cochrane Collaboration’s tool for assessing risk of bias to be at low risk of bias. Results 4 RCTs included with a total of 887 participants. They included if they had all inclusion criteria. Compared with placebo or no intervention,AT can improves DIC(p=0.015). AT reduce 28-days mortality rate in patients with DIC compared with placebo group [risk ratio(95% confidence interval),0.64(0.43-0.94),p=0.024]; 28- days mortality rate among patients without DIC administrated no significant difference between AT and placebo groups [0.99(0.66-1.49),p> 0.2]. major bleeding rate did not significantly differ between two groups [1.63(0.86-3.10),p=0.14]. there was higher rate of DIC resolution in ART-123 group than heparin group(difference 19.7%;95% CI 2.6-36.8).LPS infusion increased D-dimer levals (p<0.05 versus baseline),an effect that was blunted by heparin(p<0.01 versus placebo group). Limitations Due to small number of accessible RCTs conducted about this topic we did not added time limitation and strict conditions for follow up duration. Conclusion AT therapy in patients with DIC may result in a significant mortality reduction.ART-123 therapy more significantly improves DIC compared with heparin therapy.

Keywords:

disseminated intravascular coagulation , antithrombin , sepsis , heparin