Clinical characteristics and risk factors of tigecycline-associated hypofibrinogenaemia in critically ill patients

Abstract

Purpose To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. Methods A retrospective case-control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/ sulbactam in the hypofibrinogenaemia group were also analyzed. Results In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4-8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3-5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. Conclusion Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th-8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam.

Risk Factors for Tigecycline-Associated Hypofibrinogenemia

“…According to our research, hypofibrinogenemia was common in clinical practice, which occurred in 60.8% of the patients. This is in agreement with prior reports: in Hu’s research, 14 there were 56% developed hypofibrinogenemia, and in Zhang’s research, 15 there were 50.5% developed hypofibrinogenemia, respectively. Fibrinogen decreased by an average of 49.2%, PT, aPTT and TT increased by an average of 16.8%, 19.5% and 26.7%, respectively.…”

“…Similarly, Hu’s study also showed there is no correlation between hypofibrinogenemia and age. 14 But in their study, the age of the hypofibrinogenemia group was 63.72±15.68 years old, and that of the normal group was 55.82±18.59 years old, which were much smaller than the age of the patients in our study. Our study can better reflect the effect of tigecycline on coagulation in elderly patients.…”

“…To date, most of the published articles about tigecycline-associated hypofibrinogenemia are case reports, 8 , 11 , 12 , 16–20 and few of them are retrospective observation studies. 10 , 13 , 14 , 21 Our study was a retrospective study that included 148 patients. We found that patients who were administered tigecycline experienced a prolonged PT, a prolonged APTT, a prolonged TT, and a decreased fibrinogen level.…”

“…Consistent with the results of previous studies, the duration of medication and the baseline fibrinogen level were associated with hypofibrinogenemia. 14 However, the correlation between age and hypofibrinogenemia is controversial. In clinical practice, tigecycline is often used to treat life-threatening infections with multidrug-resistant bacteria, which is often occurred in patients with advanced age.…”

“…Inconsistent with our findings, Hu et al found that the dosage of medication and intra-abdominal infection were related to the incidence of hypofibrinogenemia. 14 This inconsistency may be due to differences in the patient characteristics. The study population in Hu’s research included mainly patients in the intensive care unit.…”