Impact of fibrinogen-to-erythrocyte suspension ratio on mortality and functional outcomes in major perioperative bleeding (Approximate Dose-Equivalent of Fibrinogen-to-Erythrocyte Suspension (ADEFES) study): protocol for a prospective observational study.

introductionEarly and balanced replacement of blood products appears to be the key factor in improving outcomes of major bleeding patients including acute trauma, cardiac, obstetric and transplant surgery patients. Definitive clinical guidance regarding the optimal ratio of blood products, including those containing fibrinogen, is still lacking. Therefore, we tested the hypothesis that increasing the fibrinogen content to erythrocyte suspension ratio improves the mortality and functional outcomes of patients undergoing surgeries with expected major bleeding. METHODS AND ANALYSIS: The Approximate Dose-Equivalent of Fibrinogen-to-Erythrocyte Suspension (ADEFES) ratio is a multicentre, prospective, observational, cohort study of patients undergoing major surgical procedures with expected major perioperative bleeding (ie, requiring packed red blood cells (PRBC)>4U/24 hours). For 5U of cryoprecipitate and 1.5 U of fresh frozen plasma (FFP), the approximate dose-equivalent for fibrinogen is considered as 1 gram of fibrinogen. Association of the ADEFES ratio at 24 hours will be assessed on the primary objective, which will consist of the composite of 30-day all-cause mortality, 30-day bleeding-specific mortality and the 'highly-dependent scores' of Katz index of independence in activities of daily living. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Ankara Bilkent City Hospital (approval no. E2-23-4265, dated 07 June 2023; Chair: Prof. Dr. F.E. Canpolat) and by the institutional review boards of all participating centres. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, as well as in compliance with national regulations on data protection and Good Clinical Practice standards. Written informed consent will be obtained from all participants prior to inclusion in the study.The results of this study will be disseminated through peer-reviewed scientific journals, presentations at national and international conferences, and communication with relevant stakeholders including clinical practitioners and healthcare institutions. If applicable, study outcomes will also be shared via institutional newsletters and digital platforms to reach a broader audience in the medical community. TRIAL REGISTRATION NUMBER: NCT06021184.