Empiric Cryoprecipitate Transfusion in Patients with Severe Hemorrhage: Results from The US Experience in the International Cryostat-2 Trial

Abstract

Background: Hypofibrinogenemia has been shown to predict massive transfusion and is associated with higher mortality in severely injured patients. However, the role of empiric fibrinogen replacement in bleeding trauma patients remains controversial. We sought to determine the effect of empiric cryoprecipitate as an adjunct to a balanced transfusion strategy (1:1:1). Study Design: Sub-analysis of the single US trauma center in a multi-center randomized controlled trial. Trauma patients (>15 years of age) were eligible if they had evidence of active hemorrhage requiring emergent surgery or interventional radiology, massive transfusion protocol (MTP) activation, and received at least one unit of blood. Transfer patients, those with injuries incompatible with life, or >3 hours from injury were excluded. Patients were randomized to standard MTP (STANDARD) or MTP plus 3 pools of cryoprecipitate (CRYO). Primary outcome: all-cause mortality at 28 days. Secondary outcomes: transfusion requirements, intra-operative and post-operative coagulation labs, and quality of life measures (Glasgow Outcome Score, GOS). Results: 49 patients were enrolled between 05/21-10/21 (CRYO-23 and STANDARD-26). Time to randomization was similar between groups (14 minutes vs 24 minutes); p=0.676. Median time to cryoprecipitate was 52 minutes [IQR, 47,60]. There were no differences in demographics, arrival physiology, laboratory values, or injury severity. Intra-operative and ICU TEG values, including functional fibrinogen, were similar between groups. There was no benefit to CRYO with respect to post-ED transfusions (intra-op and ICU through 24 hours), complications, GOS, or mortality. Conclusion: In this study of severely injured, bleeding trauma patients, empiric cryoprecipitate did not improve survival or reduce transfusion requirements. Cryoprecipitate should continue as an “on demand” addition to a balanced transfusion strategy, guided by laboratory values and should not be given empirically.