HPE CSL Managing Perioperative Bleeding handbook - Page 18

Pregnancy and post-partum anaemia, need for transfusion and invasive procedures, and maternal morbi-mortality: Hb drop compared with the reference level, percentage of patients developing anaemia (Hb < 8g/dl), requirement for PRBC transfusion or any other blood products, requirement of intrauterine balloon tamponade and/or invasive procedure (arterial ligature, or embolisation, or hysterectomy), and calculated blood loss. Regarding the population selection, evidence has shown that fibrinogen supplementation may be more efficient in patients with hypofibrinogenemia. The study population may therefore be better selected among patients with quite severe PPH at risk of developing coagulopathy. The criteria of selection was to enrol patients at the beginning of prostaglandin (sulprostone; Nalador ® ) administration, which is a time-validated second step of uterotonic treatment in the algorithm of the French PPH management guidelines (30 French guidelines). Prostaglandins are advocated after no more than 30 minutes of ongoing PPH and oxytocin failure. This inclusion criterion has been used previously. 4 Randomisation stratification by centres should protect against the bias of variable team reactivity times in taking the decision for oxytocin–prostaglandin switch. Thromboelastometric identification of coagulopathic patients was not chosen in the FIDEL protocol because most of the centres are not equipped to perform this. 18 Which fibrinogen concentrate dose to stop bleeding? The fibrinogen dose administered depends on the severity of haemorrhage as well as on the initial plasma level. Grottke demonstrated that a single dose of 2g and a target level of 1.5g/l was able to avoid death in an experimental design of liver injury in pigs. 9 In cases of severe acute obstetrical haemorrhage, larger doses of fibrinogen concentrate (4–8g) might be necessary. In a study by Kikuchi et al, 1g fibrinogen concentrate increased the plasma fibrinogen level to approximately 400mg/l only. 24 Makino et al obtained a similar increase of 32mg/ dl/g fibrinogen concentrate administered, which was not sufficient to properly correct severe hypofibrinogenemia in deep coagulopathic atonic patients. 25 The FIDEL trial aims to determine the more efficient place of a 3g dose of fibrinogen concentrate infusion, likely by administering it earlier in coagulopathic hospitalpharmacyeurope.com patients before PPH becomes life- threatening. This dose was selected on the basis of an anticipated amount of blood loss and corresponding fibrinogen loss at the time of prostaglandin administration. Because the main objective of the study is to assess the benefit associated with an early administration of fibrinogen as a therapeutic strategy, the 3g dose required in the protocol is lower than the 4–8g dose recommended in the Summary of Product Characteristics to treat the most severe PPH. Additional open-label administrations of fibrinogen concentrate will be allowed in both groups, as a rescue therapy, if the severity of the clinical situation requires it, and as per investigator discretion. Conclus