从KyberSept和OPTIMIST研究失败看肝素治疗脓毒症的潜力

Highlighting the potential of heparin in the treatment of sepsis in view of failure of KyberSept and OPTIMIST projects

严重脓毒症导致凝血系统紊乱的事实早已被人们注意到，但对其在严重脓毒症发生发展及其影响预后重要性方面的认识则是近年才获得的。

Systemic inflammation can induce blood hypercoagulability, even disseminated intravascular coagulation （DIC）, and ＂cross talk＂ exists between inflammatory and coagulation system. So anticoagulation should be helpful in the treatment of systemic inflammatory response syndrome （SIRS） or sepsis. The success in the use of recombinant human activated protein C （rhAPC） is a strong evidence to support anticoagulation strategy in the treatment of sepsis. Unexpectedly, other two anticoagulation studies, KyberSept and OPTIMIST, respectively with antithrombin and tissue factor pathway inhibitor （TFPI） failed to show improvement in 28 -day survival rate. Blame had been laid on the combined use of heparin or low molecular weight heparin （LMWH）, as it might interfere with efficacy of antithrombin and TFPI. However, no compellent evidences were found to support this hypothesis, as there was no significant difference in result between the patients with and without heparin or LMWH in the treatment groups in these two studies. Contrarily, significant differences in outcome were found between patients with and without heparin or LMWH in control groups, and the survival rate of patients with heparin or LMWH in control groups was higher than that of the treatment groups. These results strongly suggested heparin or LMWH could be effective in the treatment of sepsis. It is our understanding that any anticoagulant should have some potential effect in treatment of sepsis. Therefore, it seems to be necessary to explore the efficacy of traditional anticoagulant, and compare the effects between the new and old drugs.