Risk Factors for Tigecycline-Associated Hypofibrinogenemia

Abstract

Background With the widespread use of tigecycline, especially in elderly people infected with multidrug-resistant bacteria, the associated coagulation disorders are attracting the attention of clinicians. The risk factors of tigecycline-associated hypofibrinogenemia are still controversial. Purpose The aims of our study were to explore the related factors of hypofibrinogenemia caused by tigecycline, and to establish the risk assessment criteria for tigecycline-associated hypofibrinogenemia. Patients and Methods This was an observational retrospective cohort study of patients treated for at least 3 days with tigecycline. Hypofibrinogenemia was defined as plasma fibrinogen <2.0 g/L. Risk factors were determined using logistic regression analysis, and the risk assessment criteria were identified by using receiver operating characteristic curves. Results In total, 148 patients were included in the analysis, mean age was 77.09±15.11 years old. Ninety patients who developed hypofibrinogenemia during tigecycline treatment with mean plasma fibrinogen of 1.42 g/L were included in the hypofibrinogenemia group, the other 58 patients with mean plasma fibrinogen of 2.68 g/L were included in the normal group. In the multivariate analysis, age ( p = 0.035), tigecycline treatment duration ( p = 0.044), and baseline fibrinogen level ( p = 0.002) were independently associated with hypofibrinogenemia. An age of ≥82 years, ≥9 days of medication, and a baseline fibrinogen level of ≤3.5 g/L were selected for predicting hypofibrinogenemia. Hypofibrinogenemia was independently associated with bleeding (OR 8.96, 95% CI [1.132–70.946], p = 0.038). Conclusion Hypofibrinogenemia is a common adverse effect of tigecycline in our study. Elderly patients are more prone to developing hypofibrinogenemia after the administration of tigecycline. It is independently associated with bleeding but not death. The risk assessment criteria can help in the identification of patients with high risk of hypofibrinogenemia.

Progression of Fibrinogen Decrease during High Dose Tigecycline Therapy in Critically Ill Patients: A Retrospective Analysis

“…The decreasing group experienced a longer tigecycline treatment by two days, which is in line with the findings of Liu et al [19]. Three recent studies in critically ill patients showed similar results, with Hu et al observing a treatment duration nearly twice as long (11 vs. 6 days) if fibrinogen decreased below 200 mg/dL [18].…”

“…Intriguingly, our patients received doses that were about one-third lower than in the other studies (153 mg/day in the decreasing group, 130.4 mg/day in the non-decreasing group), but experienced comparable fibrinogen decreases, which raises the question of whether or not fibrinogen decrease is dose-dependent. In contrast to this, Liu et al only observed a trend towards higher doses in 15 patients with low fibrinogen [19]. Furthermore, the largest trial did not show an association of fibrinogen decrease with higher doses, but instead with treatment durations longer than 14 days [16].…”

“…This is comparable with Hu and co-workers [18] reporting a dose higher than 100 mg/day being a risk factor in 127 critically ill patients. All studies defined a daily dose of 200 mg as high-dose as compared to the recommended standard dose of 2 × 50 mg/day [12][13][14][16][17][18][19]. Intriguingly, our patients received doses that were about one-third lower than in the other studies (153 mg/day in the decreasing group, 130.4 mg/day in the non-decreasing group), but experienced comparable fibrinogen decreases, which raises the question of whether or not fibrinogen decrease is dose-dependent.…”

“…This is in contrast to our overweight patients receiving an approximately one-third higher dosage with a similarly comparable fibrinogen decrease. The most recent study from China only provided BMI [19], so the current literature still remains conflicted in regard to dose-dependency of coagulopathy.…”

“…In a Chinese retrospective analysis, Leng et al demonstrated decreased fibrinogen levels in 50 hospitalized patients [14]. In 2020 and 2021, four further retrospective studies with more than 600 patients were published (three from China and one from Spain), showing a possible association of tigecycline use with hypofibrinogenemia most commonly commencing on the sixth day of treatment [16][17][18][19]. In a retrospective study from China, 50.5% of 426 analyzed patients developed hypofibrinogenemia, which appeared to be more frequent in patients with kidney failure [16].…”