Systematic literature review and meta-analysis on the safety of fibrinogen concentrate versus cryoprecipitate in patients with surgical bleeding

Abstract

Fibrinogen is a protein essential to clot formation. Two plasma-derived products, fibrinogen concentrate (FC) and cryoprecipitate, are both effective options for fibrinogen replacement in patients with surgical bleeding. However, differences in composition may impact safety outcomes, particularly the risk of thromboembolic events (TEE). A systematic literature review (SLR) and meta-analysis explored the comparative safety of FC and cryoprecipitate in the management of surgical bleeding. Database searches were conducted on February 28, 2025 to identify randomized controlled trials reporting on patients with surgical bleeding (elective surgery); subgroups of interest included age (i.e., adults versus pediatrics) and surgery type. A feasibility assessment determined the viability of conducting a meta-analysis using data from the studies identified in the SLR and informed the selection of the meta-analysis approach and model. Safety outcomes of interest were selected based on the availability of data in at least two trials: All TEEs, deep vein thrombosis (DVT), pulmonary embolism (PE), Any Adverse Events (AE), and serious AEs (SAE). The SLR identified seven studies—all were considered feasible for meta-analysis. In the base case, the odds of DVT events in patients in the FC group were significantly lower than in the cryoprecipitate group (odds ratio [OR]: 0.31 [95% confidence interval (CI): 0.12, 0.81]). FC was also associated with lower odds of Any AEs (OR: 0.70 [95% CI: 0.52, 0.94]); however, statistical significance was not maintained across all sensitivity analyses, despite a consistent direction of effect. No statistically significant differences were observed for All TEEs, PE, or SAEs. In this meta-analysis, FC was associated with lower odds of DVT versus cryoprecipitate in the management of surgical bleeding, while the base-case analysis indicated lower odds of Any AEs; however, statistical significance for the Any AEs finding was not maintained across all sensitivity analyses. No clear differences were observed for All TEEs, PE, or SAEs. These findings should be interpreted in the context of the outcome-specific certainty of evidence, the limited evidence base, and clinical and statistical heterogeneity across studies. Further adequately powered studies are needed to better characterize the comparative safety of FC and cryoprecipitate across surgical settings.