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鉴于KyberSept和OPTIMIST项目的失败,突显肝素在脓毒症治疗中的潜力

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

作者信息

Lin Hong-yuan

机构信息

Intensive Care Unit, the First Affiliated Hospital of General Hospital of PLA, Beijing 100037, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Mar;19(3):134-7.

Abstract

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 compelling evidence was 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.

摘要

全身炎症可诱导血液高凝状态,甚至引发弥散性血管内凝血(DIC),且炎症系统与凝血系统之间存在“串扰”。因此,抗凝治疗可能有助于全身炎症反应综合征(SIRS)或脓毒症的治疗。重组人活化蛋白C(rhAPC)的成功应用是支持脓毒症抗凝治疗策略的有力证据。出乎意料的是,另外两项分别使用抗凝血酶和组织因子途径抑制剂(TFPI)的抗凝研究(KyberSept和OPTIMIST)未能显示28天生存率有所改善。有人将此归咎于肝素或低分子量肝素(LMWH)的联合使用,因为其可能会干扰抗凝血酶和TFPI的疗效。然而,并未找到确凿证据支持这一假设,因为在这两项研究的治疗组中,使用和未使用肝素或LMWH的患者之间结果并无显著差异。相反,在对照组中,使用和未使用肝素或LMWH的患者之间结果存在显著差异,且对照组中使用肝素或LMWH的患者生存率高于治疗组。这些结果强烈表明肝素或LMWH可能对脓毒症治疗有效。我们的理解是,任何抗凝剂在脓毒症治疗中都应具有一定潜在作用。因此,探索传统抗凝剂的疗效,并比较新旧药物的效果似乎很有必要。

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