Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial

Abstract

Objective To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. Design Multicentre, double‐blind, randomised placebo‐controlled trial. Setting: 30 French hospitals. Population Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. Methods Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. Main outcome measures Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity–mortality within 6 ± 2 weeks after delivery. Results 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66–1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. Conclusions As previous placebo‐controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. Tweetable abstract Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Haematological management of major haemorrhage: a British Society for Haematology Guideline

“…A low fibrinogen level during PPH is an important predictor of the severity of PPH and poor clinical outcome 84,85 . RCTs do not support the early unselected use of fibrinogen concentrate replacement therapy, 86,87 and administering fibrinogen supplementation to women with PPH who have fibrinogen levels of >2 g/l is unlikely to have added benefit 88 . A recent pilot cluster RCT in severe PPH highlighted practical challenges around the early delivery of cryoprecipitate in PPH, and further trials are required to evaluate clinical outcomes 89 …”

Emergencies in obstetric anaesthesia: a narrative review

“…Hypofibrinogenaemia can develop well before prolongation of the activated partial thromboplastin time/prothrombin time and thrombocytopenia, particularly after placental abruption [52–55]. Despite this, trials of empiric fibrinogen concentrate administration without laboratory testing in PPH > 1500 ml have been disappointing (Table 3) [56–58]. Using point‐of‐care viscoelastic assays during PPH to guide fibrinogen concentrate administration did not reduce transfusion rates or blood loss [56].…”

“…(Table 3) [56][57][58]. Using point-of-care viscoelastic assays during PPH to guide fibrinogen concentrate administration did not reduce transfusion rates or blood loss [56].…”

The Role of Thromboelastography during the Management of Postpartum Hemorrhage: Background, Evidence, and Practical Application

“…38 Two studies, undertaken by Wikkelsø et al and the Fibrinogen in Hemorrhage of Delivery (FIDEL) group, have investigated empirical fibrinogen concentrate replacement during PPH >1,000 mL with ongoing bleeding or after failed firstline uterotonics. 35,39 Neither study used either laboratory or POC-VHA to guide therapy. Wikkelsø et al gave 2 g of fibrinogen concentrate and found no difference in their primary or secondary outcomes of RBC transfusion or bleed volume.…”