切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2016, Vol. 02 ›› Issue (03) : 156 -161. doi: 10.3877/cma.j.jssn.2096-1537.2016.03.004

所属专题: 重症医学 总编推荐 文献

述评

脓毒症抗凝治疗的现实与未来
章志丹, 李鑫, 马晓春   
  • 收稿日期:2016-07-18 出版日期:2016-08-28
  • 通信作者: 马晓春

The current situation and future of anticoagulant therapy for sepsis

Zhidan Zhang, Xin Li, Xiaochun Ma   

  • Received:2016-07-18 Published:2016-08-28
  • Corresponding author: Xiaochun Ma
  • About author:
    Corresponding author: Ma Xiaochun, Email:
引用本文:

章志丹, 李鑫, 马晓春. 脓毒症抗凝治疗的现实与未来[J]. 中华重症医学电子杂志, 2016, 02(03): 156-161.

Zhidan Zhang, Xin Li, Xiaochun Ma. The current situation and future of anticoagulant therapy for sepsis[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2016, 02(03): 156-161.

脓毒症是感染诱发的宿主反应失调所导致危及生命的器官功能障碍的一种临床综合征,通常伴有凝血功能障碍的发生。脓毒症诱发的微血管内血栓形成具有"双刃剑"的作用。感染局部的微血管内血栓形成能够发挥免疫血栓的防御功能,促进病原微生物的清除,对机体是有利的。相反,弥散性微血管内血栓形成是脓毒症相关多器官功能障碍的重要发病机制,为脓毒症的抗凝治疗提供了充足的理论基础。尽管针对脓毒症抗凝治疗的临床研究尚存在争议,但并不能因此而全面否定抗凝治疗对脓毒症的价值。我们应当全面评估脓毒症患者的凝血功能障碍,寻找抗凝治疗的合适时机以及可能受益的人群,并采用优化的抗凝治疗策略,为脓毒症的抗凝治疗寻求更为合理有效的方案。

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is usually associated with coagulation dysfunction. Sepsis induced microvascular thrombosis works as a ″double-edged sword″. The local microvascular thrombosis can play a role of host defense as immunothrombosis and promote the removal of pathogenic microorganisms. In contrast, disseminated intravascular thrombosis is an important pathogenesis of sepsis related multiple organ dysfunction, which provides a theoretical basis for the anticoagulation therapy. Although there is controversy about the clinical trials on the anticoagulation therapy for sepsis, the clinical value of anticoagulation therapy can not be completely denied. We should comprehensive evaluate the coagulation function of septic patients to find the optimal timing for anticoagulant therapy and the optimal patient group who may get benefit from the anticoagulant therapy, and further optimize the strategy of anticoagulant therapy for septic patients.

[1]
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3)[J]. JAMA, 2016, 315(8):801–810.
[2]
Okamoto K, Tamura T, Sawatsubashi Y. Sepsis and disseminated intravascular coagulation[J]. J Intensive Care, 2016, 4:23.
[3]
Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock; 2012[J]. Crit Care Med, 2013, 41(2):580–637.
[4]
Oda S, Aibiki M, Ikeda T, et al. The Japanese guidelines for the management of sepsis[J]. J Intensive Care, 2014, 2(1):55.
[5]
Angus DC, van der Poll T. Severe Sepsis and Septic Shock[J]. N Engl J Med, 2013, 369(9):840–851.
[6]
Wiersinga WJ, Leopold SJ, Cranendonk DR, et al. Host innate immune responses to sepsis[J]. Virulence , 2014, 5(1):36–44 .
[7]
Semeraro N, Ammollo CT, Semeraro F, et al. Coagulopathy of Acute Sepsis[J]. Semin Thromb Hemost , 2015, 41(6):650–658.
[8]
Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis[J]. Proc Natl Acad Sci U S A, 2010, 107(36):15880–15885.
[9]
Ammollo CT, Semeraro F, Xu J, Esmon NL, et al. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation[J]. J Thromb Haemost, 2011, 9(9):1795–1803.
[10]
Ito T. PAMPs and DAMPs as triggers for DIC[J]. J Intensive Care, 2014, 2(1):67.
[11]
Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity[J]. Nat Rev Immunol , 2013, 13(1):34–45.
[12]
Seeley EJ, Matthay MA, Wolters PJ. Inflection points in sepsis biology: from local defense to systemic organ injury[J]. Am J Physiol Lung Cell Mol Physiol , 2012, 303(5):355–363.
[13]
Soerensen KE, Olsen HG, Skovgaard K, et al. Disseminated intravascular coagulation in a novel porcine model of severe staphylococcus aureus sepsis fulfills human clinical criteria[J]. J Comp Pathol, 2013, 149(4):463–474.
[14]
Simmons J, Pittet JF. The coagulopathy of acute sepsis[J]. Curr Opin Anaesthesiol, 2015, 28(2):227–236.
[15]
Abraham E, Reinhart K, Opal S, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial[J]. JAMA, 2003, 290(2):238–247.
[16]
Wunderink RG, Laterre PF, Francois B, et al. Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia a randomized trial[J]. Am J Respir Crit Care Med , 2011, 183(11):1561–1568.
[17]
Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial[J]. JAMA, 2001, 286(15):1869–1878.
[18]
Allingstrup M, Wetterslev J, Ravn FB, et al. Antithrombin Ⅲ for critically ill patients[J]. Cochrane Database Syst Rev, 2016, 2:CD005370.
[19]
Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis[J]. N Engl J Med, 2001, 344(10):699–709.
[20]
Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock[J]. Intensive Care Med, 2004, 30(4):536–555.
[21]
Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death[J]. N Engl J Med, 2005, 353(13):1332–1341.
[22]
Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock[J]. N Engl J Med, 2012, 366(22):2055–2064.
[23]
Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012[J]. Crit Care Med, 2013, 41(2):580–637.
[24]
Vincent JL, Ramesh MK, Ernest D, et al. A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy ofrecombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation[J]. Crit Care Med, 2013, 41(9):2069–2079.
[25]
Yamakawa K, Aihara M, Ogura H, et al. Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis[J]. J Thromb Haemost, 2015 , 13(4):508–519.
[26]
Jaimes F, De La Rosa G, Morales C, et al. Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study)[J]. Crit Care Med, 2009, 37(4):1185–1196.
[27]
Wang C, Chi C, Guo L, et al. Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis[J]. Crit Care, 2014, 18(5):563.
[28]
Zarychanski R, Abou-Setta AM, Kanji S, et al. The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis[J]. Crit Care Med, 2015, 43(3):511–518.
[29]
Allen KS, Sawheny E, Kinasewitz GT. Anticoagulant modulation of inflammation in severe sepsis[J]. World J Crit Care Med, 2015, 4(2):105–115.
[30]
Fiusa MM, Carvalho-Filho MA, Annichino-Bizzacchi JM, et al. Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective[J]. BMC Med, 2015, 13:105.
[31]
Umemura Y, Yamakawa K, Ogura H, et al. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials[J]. J Thromb Haemost, 2016, 14(3):518–530.
[32]
Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan[J]. Int J Hematol, 2016, 103(3):253–261.
[33]
Iba T, Saitoh D, Wada H, et al. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a secondary survey[J]. Crit Care, 2014, 18(5):497.
[34]
Yoshimura J, Yamakawa K, Ogura H, et al. Benefit profile of recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis[J]. Crit Care, 2015, 19:78.
[35]
Semeraro N, Ammollo CT, Semeraro F, et al. Sepsis, thrombosis and organ dysfunction[J]. Thromb Res, 2012, 129(3):290–295.
[36]
Allam R, Kumar SV, Darisipudi MN, et al. Extracellular histones in tissue injury and inflammation[J]. J Mol Med (Berl), 2014, 92(5):465–472.
[37]
Xu J, Zhang X, Pelayo R, et al. Extracellular histones are major mediators of death in sepsis[J]. Nat Med, 2009, 15(11):1318–1321.
[38]
Li Y, Liu Z, Liu B, et al. Citrullinated histone H3: a novel target for the treatment of sepsis[J]. Surgery, 2014, 156(2):229–234.
[39]
Iba T, Hashiguchi N, Nagaoka I, et al. Heparins attenuated histone-mediated cytotoxicity in vitro and improved the survival in a rat model of histone-induced organ dysfunction[J]. Intensive Care Med Exp, 2015, 3(1):36.
[40]
Wildhagen KC, García de Frutos P, Reutelingsperger CP, et al. Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis[J]. Blood, 2014, 123(7):1098–1101.
[41]
Wildhagen KC, Ding R, Hao D, Guo R, et al. Treatment with unfractionated heparin attenuates Coagulation and Inflammation in Endotoxemic Mice[J]. Thromb Res, 2011, 128(6):160–165.
[42]
Zhao D, Ding R, Mao Y, et al. Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses[J]. Inflammation, 2012, 35(6):1825–1832.
[43]
Li X, Zheng Z, Li X, et al. Unfractionated heparin inhibits lipopolysaccharide-induced inflammatory response through blocking p38 MAPK and NF-κB activation on endothelial cell[J]. Cytokine, 2012, 60(1):114–121.
[44]
Luan ZG, Naranpurev M, Ma XC. Treatment of low molecular weight heparin inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats[J]. Inflammation, 2014, 37(3):924–932.
[45]
Yini S, Heng Z, Xin A, et al. Effect of unfractionated heparin on endothelial glycocalyx in a septic shock model[J]. Acta Anaesthesiol Scand, 2015, 59(2):160–169.
[46]
Wang L, Liu Z, Dong Z, et al. Azurocidin-induced inhibition of oxygen metabolism in mitochondria is antagonized by heparin[J]. Exp Ther Med, 2014, 8(5):1473–1478.
[47]
Iba T, Miki T, Hashiguchi N, et al. Combination of antithrombin and recombinant thrombomodulin modulates neutrophil cell-death and decreases circulating DAMPs levels in endotoxemic rats[J]. Thromb Res, 2014, 134(1):169–173.
[48]
Annane D, Buisson CB, Cariou A, et al. Design and conduct of the activated protein C and corticosteroids for human septic shock (APROCCHSS) trial[J]. Ann Intensive Care, 2016, 6(1):43.
[1] 韩媛媛, 热孜亚·萨贝提, 冒智捷, 穆福娜依·艾尔肯, 陆晨, 桑晓红, 阿尔曼·木拉提, 张丽. 组合式血液净化治疗对脓毒症患者血清炎症因子水平和临床预后的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 272-278.
[2] 孟建标, 张庚, 焦燕娜. 脓毒症合并心功能障碍患者早期肠道微生态改变的探讨[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 279-285.
[3] 陈宇, 冯芳, 张露, 刘健. 基于生物信息学分析筛选脓毒症心肌病关键致病基因[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 286-291.
[4] 张晓燕, 肖东琼, 高沪, 陈琳, 唐发娟, 李熙鸿. 转录因子12过表达对脓毒症相关性脑病大鼠大脑皮质的保护作用及其机制[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 540-549.
[5] 魏徐, 张鸽, 伍金林. 新生儿脓毒症相关性凝血病的监测和治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 379-386.
[6] 姚咏明. 如何精准评估烧伤脓毒症患者免疫状态[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 552-552.
[7] 窦上文, 邓欢, 刘邦锋, 岳高远志, 朱华财, 刘永达. 术前复查尿培养在预测微通道经皮肾镜取石术相关感染并发症中的作用[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 361-366.
[8] 李云锋, 俞永江. 抗凝治疗的老年腹股沟疝患者围手术期治疗研究进展[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(03): 247-250.
[9] 李伟, 卓剑, 黄川, 黄有攀. Lac、HO-1、sRAGE、CRP/ALB表达及脓毒症并发ARDS危险因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 514-516.
[10] 李翠平, 陈晓燕, 钱师宇, 林惠珠, 曾彩辉, 阳莉, 卢建溪. 不同抗凝剂保存液对脐血培养的NK细胞增殖及杀伤效应的影响[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 572-576.
[11] 苗软昕, 乔晞. Toll样受体在脓毒症性急性肾损伤中的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 210-214.
[12] 高超, 巢杰, 邱海波. T-bet:脓毒症免疫失衡中Th17细胞的新型调节分子[J]. 中华重症医学电子杂志, 2023, 09(03): 280-285.
[13] 杨翔, 郭兰骐, 谢剑锋, 邱海波. 宏基因组二代测序在脓毒症病原体诊断中的应用进展[J]. 中华重症医学电子杂志, 2023, 09(03): 292-297.
[14] 谭睿, 王晶, 於江泉, 郑瑞强. 脓毒症中高密度脂蛋白、载脂蛋白A-I和血清淀粉样蛋白A的作用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(06): 749-753.
[15] 蔡荇, 郑瑞强. 肝素结合蛋白在脓毒症中的应用及研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(04): 487-490.
阅读次数
全文


摘要