Optimal fibrinogen threshold in non-traumatic massive bleeding: a multicenter retrospective observational study
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Source: Critical Care
Authors: Siying Chen, Shiyu Liu, Bingkui Ren, Yuping Zhang, Jinglong Dai, Ziyan Ye, Lu Xu, Yun Fan, Chuanbao Li, Zhengying Jiang, Qian Liu, Kang Zou, Zhiyuan Zhang, Wenqing Lian, Shuangling Li, Peng Wang, Lu Ke, Weibang Pan, Wenjian Mao, Feng Guo, Yi-miao Xu, Ting Lin, Wenjun Tan, Weihai Wei, Qiuhua Yang, Jun Duan, Dezhi Ren, Zheng Duan, Luchuan Xing, Hua Xu, Lin Dou, Wensong Su, Linghui Zhan, Fengxue Zhu, Zhigang Chang
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Hospital, Peking University People's Hospital, Chongqing University, Chongqing Cancer Hospital, Gannan Medical University, First Affiliated Hospital of Gannan Medical University, Peking University First Hospital, Nanjing General Hospital of Nanjing Military Command, Nanjing University, Sir Run Run Shaw Hospital, Zhejiang University, First Affiliated Hospital of Xi'an Jiaotong University, First Hospital of Xi'an, China-Japan Friendship Hospital, Shengli Oilfield Central Hospital, Tianjin First Center Hospital, Fifth Tianjin Central Hospital, Xiamen University, Zhongshan Hospital of Xiamen University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W7148506993