WHAT IS A MASSIVE TRANSFUSION? A SCOPING REVIEW TO INFORM AN INTERNATIONAL CONSENSUS DEFINITION.

Abstract

Background: No standardized or universally accepted definition for massive transfusion (MT) currently exists, making it difficult to compare safety and efficacy data across studies on critically bleeding patients. The Bleeding Academic Research Consortium successfully standardized definitions for major bleeding in both surgical and non-surgical patients, providing proof of principle for a similar approach to be adopted for the definition of MT. Aim(s): To identify and evaluate all MT definitions used in randomized controlled trials (RCTs) to date to inform the development of an international consensus definition for MT. Method(s): We performed a scoping review of RCTs related to MT. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library were searched from inception until 11 August 2022 without language restriction. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies were required to: (1) be an RCT; (2) include an adult patient population with an acquired bleeding disorder who had received, or were anticipated to receive, an MT in any clinical setting; and (3) have a specified definition for MT. Conference abstracts, opinion pieces, clinical guidelines, narrative reviews, post hoc analyses, laboratory-only studies, and studies including only paediatric or non-human subjects were excluded. Result(s): of the 8,460 distinct references identified from the initial search, 30 studies were included (19 published, 11 ongoing). Several landmark trials on critically bleeding patients, including CRASH-2, were excluded as they did not report a definition for MT. Table 1 highlights the lack of uniformity in MT definitions used to date. Fifteen distinct definitions of MT have been used in RCTs across 4 different specialties (trauma, obstetrics/gynecology, cardiothoracic surgery, and orthopedic surgery) since 1986. Most were based on number of units of RBCs or whole blood administered within a certain time interval. None included other blood products (e.g., platelets, plasma), and some did not specify a time interval during which administration needed to take place. The most common definition of MT (featuring in 10/30 = 33% of studies) was the classic definition of >=10 units of RBCs in 24 hours (h), with a trend in more recent studies towards the use of shorter time frames (e.g., >=4 RBCs in 6 h in the TrauCC study registered in 2016 and T-STORHM study published in 2019; >=3 RBCs in 1 h in a Spanish trial registered in 2017 and the PROCOAG study published in 2021). The classic definition (>=10 RBCs in 24 h) was favored in trauma (featuring in 9/15 = 60% of trauma trials), whereas the most frequently used definition in obstetrics/gynecology was >5 units of whole blood (featuring in 3/6 = 50% of obstetrics/gynecology trials). Summary/Conclusion: Significant heterogeneity exists in the definitions used for MT in RCTs to date. Our findings provide a basis for the development of a consensus definition for MT (e.g., through a modified Delphi process) that can be applied consistently across future trials, which balances the strengths and weaknesses of previous definitions in a specialtyspecific manner.