Tigecycline was approved in 2005 by the US Food and Drug Administration (FDA) and since then has been used as a last-resort treatment option against severe infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter spp . The combination of tigecycline with another antimicrobial agent is considered even in the treatment of nosocomial pneumonia due to pandrug-resistant Acinetobacter baumannii infections . In our retrospective analysis across 18 months, the maximum species of pathogens of these severe infected patients using tigecycline was multi-drug resistant Acinetobacter baumannii, with a percentage of 63.9% (53/83). At the meantime, the vast majority of these patients were treated for ventilator-associated and healthcare-acquired pneumonia, with a percentage of 87.9% (73/83).
Prescribing information provided by the manufacturer suggests that tigecycline might affect the coagulation function, although an uncommon adverse reaction (incidence < 2%) . Tigecycline associated hypofibrinogenemia was not mentioned in the prescribing information. However, there are some literature reports about tigecycline associated hypofibrinogenemia in recent years [13–17], giving first place to case report [15–18], occasionally but significant. Moreover, Routsi et al.  in a study of 45 ICU patients on tigecycline reported that a higher dose of tigecycline treatment resulted in a decrease in fibrinogen, along with an increase in INR and APTT values, and these alterations were reversible almost immediately following tigecycline discontinuation. Zhang et al.  found a significantly lower fibrinogen level in patients treated with tigecycline, and the fibrinogen level returned to normal after the cessation of tigecycline. The strong time-dependent association of fibrinogen and the use of tigecycline and its reversal after discontinuation might point to a causative role of the drug.
Tigecycline was approved for administration at a loading dose of 100 mg followed by 50 mg twice daily . However, high percentages of treatment failure and higher mortality among patients treated with the standard dose of tigecycline were documented [21–24]. Higher doses have been applied especially in patients with severe bacterial infections, but data addressing coagulation variables are limited. According to our study, in the higher-dose group, the fibrinogen level did not rebound after the cessation of tigecycline, but kept on drop, showing a more pronounced impact on fibrinogen than recommended dose. Zhang et al.  reported that the fibrinogen level decreased more in the higher-dose group, showing significant difference from recommended-dose group.
The use of tigecycline in patients with more severe reductions infibrinogen may put patients at an increased risk of bleeding. Our find that the new-onset bleeding and fibrinogen drop showed almost simultaneously might point to a causative role of this drug. Fibrinogen drop should not be the only reason for bleeding. Fibrinogen decreases, combined with prolongation of clotting time or/and platelet decreases, can cause severe bleeding, increased hospitalization, and mortality. Although it was not mentioned in the prescribing information, and there was a low proportion of new-onset bleeding in our study and few reports in the past, the importance of this phenomenon can’t be overstated.
Being structurally similar to tetracycline class antibiotics, tigecycline can influence coagulation either via an effect on the vitamin-K-producing flora of the gut or via a direct drug effect on the coagulation cascade . Indeed, alterations of other coagulation indexes, such as prolongation of APTT、PT and INR in patients treated with tigecycline have been reported. However, decreased fibrinogen levels have not been described in the clinical trials. Whether the decreased concentration of fibrinogen was due to increased consumption or impaired synthesisis questioned. It was recommended that the cause of fibrinogen decrease should be looked for in the field of reduced synthesis.
The study reported here must be considered preliminary due to its small sample and observational characteristics. It is not routine to monitor coagulation function during tigecycline treatment in clinical works up to now, and the data we collected was with high dispersivity. The data after tigecycline withdrawal was even fewer, because these subjects were critically ill patients, many of whom were ended with death missing data after tigecycline withdrawal.
We believe that monitoring coagulation markers, including fibrinogen should be considered in all patients receiving tigecycline. If patients do develop hypofibrinogenemia or active bleeding begins, one should consider stopping tigecycline. Usually, along with the fibrinogen improvement, the coagulation function would rebound after tigecycline withdrawal. It was recommend that fibrinogen levels of <1.2 g/L should be treated with cryoprecipitate, or fibrinogen infusion should be given . We envision further studies to clarify the mechanisms and risk factors for the observed effects.