PPH protocol
The patients were managed medically and surgically according to the most recent French guidelines 4,20,21. Antifibrinolytic prophylaxis was given according to the investigators’ choice in both groups. Administration of tranexamic acid (TXA) or fibrinogen within 48h prior to inclusion was a non-inclusion criteria, but was allowed after inclusion 19. After intravenous infusion of the investigational medicinal product (IMP: 3 g fibrinogen concentrate or placebo), the decision to transfuse blood or not was taken based on European guidelines 22. Administration of fibrinogen concentrate (Clottafact®, LFB, Les Ulis – France) beyond 60 minutes after the start of the IMP and of other rescue procedures were allowed as safety measures following strict rules to control bias19. The start time of the IMP infusion corresponded to H0. Blood samples were taken at H0, H2, H6 and D2 (Figure S1). The fibrinogen dose was set according to a preliminary kinetics study.