Tigecycline-Associated Hypofibrinogenemia and Major Bleeding: Incidence, Predictors, and Clinical Outcomes in a Retrospective Cohort

Background: Tigecycline-associated hypofibrinogenemia has been increasingly reported, but its clinical significance and predictors of bleeding remain unclear. We assessed incidence, predictors, and bleeding outcomes in routine care. Methods: We conducted a retrospective cohort study of adults receiving tigecycline at a tertiary medical center in 2022. Hypofibrinogenemia was defined as fibrinogen less than 200 mg/dL during treatment. Major bleeding was defined using International Society on Thrombosis and Haemostasis criteria. Patients were followed from treatment initiation until 7 days after discontinuation. Multivariable logistic regression identified independent predictors of hypofibrinogenemia and major bleeding. Receiver operating characteristic analyses determined optimal cut-offs using the Youden index. Results: Among 231 included patients, 98 (42.4%) developed hypofibrinogenemia. Major bleeding occurred in 52 (22.5%) patients and was more frequent in patients with hypofibrinogenemia (30.6% vs 16.5%, p = 0.01). Independent predictors of hypofibrinogenemia included baseline fibrinogen less than 350 mg/dL (aOR: 3.27, 95% CI: 1.73– 6.19), hemodialysis (aOR: 2.34, 95% CI: 1.02– 5.38), peptic ulcer disease (aOR: 7.10, 95% CI: 1.38– 38.53), and cumulative tigecycline dose greater than 1125 mg (aOR: 2.60, 95% CI: 1.40– 4.84). Hypofibrinogenemia was the only independent predictor of major bleeding (aOR: 2.25, 95% CI: 1.14– 4.44). Conclusion: Hypofibrinogenemia was common during tigecycline therapy and independently associated with major bleeding. Baseline fibrinogen and cumulative exposure may help identify high-risk patients. Routine fibrinogen monitoring should be considered during tigecycline treatment. Plain Language Summary: Tigecycline is often used when infections are difficult to treat, especially when bacteria are resistant to many standard antibiotics. However, this drug can sometimes lower fibrinogen, a clotting protein that helps prevent bleeding. This change may not be noticed right away, but it can become clinically important during treatment. We studied hospitalized adults who received tigecycline at a tertiary medical center. Our goal was to find out how often low fibrinogen developed, which patients were at higher risk, and whether this complication was associated with bleeding. We found that hypofibrinogenemia was common and was linked to major bleeding. Higher-risk groups included people with lower fibrinogen levels before treatment, those undergoing hemodialysis, those with peptic ulcer disease, and those who received a greater total amount of tigecycline. Our results support the use of fibrinogen monitoring before and during tigecycline treatment. This may be particularly helpful when longer treatment courses are expected or when patients already have factors that increase bleeding risk.