Fibrinogen levels drop early in postpartum hemorrhage (PPH), and low fibrinogen levels predict outcomes. There is increasing interest in replacing fibrinogen early in severe PPH and this systematic review’s aim was to assess if early fibrinogen replacement therapy improves outcomes in severe PPH.

We searched the following databases from inception to June 2019: CDSR and CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, PubMed, Transfusion Evidence Library, LILACS, Web of Science Conference Proceedings Citation Index-Science, ClinicalTrials.gov and the WHO International Clinical Trials Registry Portal. We included randomized (RCT) and well-designed controlled observational studies where fibrinogen replacement therapy was given early (within 90 minutes of bleeding) compared with standard protocol in pregnant women > 24 weeks’ gestation who developed PPH, defined as estimated blood loss ≥500 mL up to 24 hours post-delivery. Two independent reviewers extracted and reviewed the data on the primary outcome of allogeneic blood transfusion at 24 hours after intervention and secondary outcomes including all-cause mortality, rate of thrombosis, and the need for surgical and non-surgical interventions.

We identified 5 eligible studies: 2 completed (total of 299 women) RCTs comparing fibrinogen concentrate with placebo, and 3 ongoing RCTs. There was no completed study assessing cryoprecipitate transfusion. There was variation of: timings of intervention administration; severity of PPH; fibrinogen doses and use of tranexamic acid. There was insufficient evidence that early administration of fibrinogen in PPH reduces the need for allogeneic blood transfusion at 24 hours (risk ratio 0.83 (95% CI 0.54–1.26), P = 0.38) (2 trials, 299 participants) or improves other outcomes. Both studies were underpowered to answer our outcomes.

There is a lack of evidence that early fibrinogen replacement therapy improves outcomes in PPH. Future studies are needed to address this, underpinned by data on the optimal fibrinogen dose, protocol-driven approaches versus targeted therapy, and cost-effectiveness of cryoprecipitate versus fibrinogen concentrate therapy in PPH.

产后出血（PPH）早期纤维蛋白原水平下降，而纤维蛋白原水平低则预示了结局。在重度PPH中早期更换纤维蛋白原的兴趣日益浓厚，该系统评价的目的是评估早期纤维蛋白原替代疗法是否可以改善重度PPH中的预后。

从开始到2019年6月，我们搜索了以下数据库：CDSR和CENTRAL（The Cochrane Library），MEDLINE，Embase，CINAHL，PubMed，输血证据库，LILACS，Web of Science会议论文集引文索引，Science，ClinicalTrials.gov和WHO国际临床试验注册中心门户网站。我们纳入了随机（RCT）和设计良好的对照观察性研究，其中妊娠> 24周且发生PPH的孕妇（定义为失血量≥500），与标准方案相比，较早（在出血90分钟之内）给予了纤维蛋白原替代治疗。交货后24小时内不得超过mL。两名独立的审查者提取并审查了干预后24小时同种异体输血的主要结果和次要结果（包括全因死亡率，血栓形成率以及是否需要手术和非手术干预）的数据。

我们确定了5项合格研究：2项（共299名女性）完成的RCT（将纤维蛋白原浓缩物与安慰剂进行比较）和3项正在进行的RCT。尚未完成评估冷沉淀输血的研究。存在以下变化：干预管理的时间安排；PPH的严重程度；纤维蛋白原剂量和氨甲环酸的用途。没有足够的证据表明在PPH中早期给予纤维蛋白原可减少24小时异体输血的需要（风险比0.83（95％CI 0.54–1.26），P = 0.38）（2个试验，299名参与者）或改善了其他结局。两项研究均不足以回答我们的结果。

缺乏证据表明早期纤维蛋白原替代疗法可改善PPH的预后。在PPH中，最佳纤维蛋白原剂量，方案驱动方法与靶向治疗的数据以及冷冻沉淀与纤维蛋白原浓缩物治疗的成本效益相关的数据，需要进一步的研究来解决。