• Libing Jiang, Shouyin Jiang, Xia Feng, Yuefeng Ma, and Mao Zhang.
• Department of Emergency Medicine, Second Affiliated Hospital, School of Medicine & Institute of emergency Medicine, Zhejiang University, Hangzhou, China.
• BMJ Open. 2014 Jan 1;4(12):e006770.

IntroductionSepsis is the leading cause of mortality in non-cardiological critically ill patients. There are as many as 20 million cases of sepsis annually worldwide, with a mortality rate of around 35%. It has been reported that the dysregulation of haemostatic system due to the interaction between coagulation system and inflammatory response is a strong predictor of mortality in patients with severe sepsis. In this context, several anticoagulants have been evaluated in recent years. However, the results of these studies were inconsistent and even contradictory. In addition, there is insufficient evidence comparing the efficacy and safety of different anticoagulants. The purpose of our study is to carry out a systematic review and network meta-analysis comparing the efficacy and safety of different anticoagulants for severe sepsis based on existing randomised controlled trials (RCTs) and ranking these anticoagulants for practical consideration.Methods And AnalysisPubMed, EMBASE and Cochrane Library databases will be systematically searched for eligible studies. Randomised controlled trials (RCT) on anticoagulant therapy for severe sepsis with multiple outcome measures will be included. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are mortality and bleeding events. The secondary outcomes include the length of intensive care stay, the length of hospital stay and duration of mechanical ventilation. Direct pairwise meta-analysis (DMA), indirect treatment comparison meta-analysis (ITC) and network meta-analysis (NMA) will be conducted to compare different anticoagulants.Ethics And DisseminationEthical approval is not required given that this is a protocol for a systematic review. The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at a relevant conference.Trial Registration NumberThis protocol has been registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42014013886.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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