Optimal fibrinogen threshold in non-traumatic massive bleeding: a multicenter retrospective observational study

Current guidelines make no recommendation regarding appropriate fibrinogen replacement thresholds for non-traumatic massive bleeding. We aimed to determine the optimal post-treatment fibrinogen level associated with survival in critically ill patients with non-traumatic massive bleeding. This multicenter retrospective cohort study enrolled adult ICU patients with non-traumatic massive bleeding and hypofibrinogenemia (fibrinogen <2.0 g/L) from 12 centers in China (2018–2025). Maximum fibrinogen level (FIBmax) achieved during treatment within 3 Days of hemorrhage onset was the primary predictor. We used the Boruta algorithm for variable selection, multivariable logistic regression to assess the independent association between FIBmax and hospital mortality, restricted cubic splines to examine dose-response relationships, and pairwise group comparisons with Bonferroni correction to identify the optimal threshold. Among 358 patients (median age 59 years; 62.6% male), 74 (20.7%) died during hospitalization. FIBmax was independently associated with hospital mortality after adjustment for confounders (OR 0.37 per g/L increase; 95% CI 0.25–0.57; P < 0.001). Adding FIBmax to the base model significantly improved discrimination (AUC 0.899 vs. 0.868; P = 0.017), calibration (Hosmer-Lemeshow P = 0.096 vs. 0.031), and reclassification (NRI 0.814; IDI 0.076). Restricted cubic spline analysis revealed a non-linear dose-response relationship (P for non-linearity = 0.026), with an inflection point at 2.03 g/L. Pairwise comparisons identified a significant hospital mortality transition at 2.0 g/L: patients with FIBmax of 1.5–2.0 g/L had 3.23-fold higher hospital mortality compared to those achieving 2.0–2.5 g/L (P = 0.004), representing the only significant transition point across all adjacent group comparisons. Hospital mortality plateaued at higher levels, with no additional benefit observed above 2.5 g/L. Patients achieving FIBmax ≥ 2.0 g/L had hospital mortality of 10.1% versus 48.0% for those below this threshold (P < 0.001). In critically ill patients with non-traumatic massive bleeding, a post-treatment fibrinogen level of 2.0–2.5 g/L appears optimal, and 2.0 g/L may represent a potential therapeutic threshold.