Nomogram for the prediction of tigecycline-induced hypofibrinogenemia in Chinese population

Tigecycline has been widely used for multi-drug resistant bacterial infections in China. Although many studies have reported the risk factors for tigecycline-induced hypofibrinogenemia, it remains unknown whether valproic acid or voriconazole in combination with tigecycline is related to fibrinogen decline, as both drugs could lead to coagulation disorders. The aim of the study was to develop a nomogram for the prediction of tigecycline-induced hypofibrinogenemia. This is a multi-center retrospective case-control study. The primary outcomes for the nomograms were tigecycline-induced hypofibrinogenemia. The nomograms were developed from logistic regression models with least absolute shrinkage and selection operator (LASSO) regression for variable selection. Model performance was assessed via calibration plots, and models were internally validated using bootstrapping on a validation cohort. In total, 2362 patients were screened, of which 611 were eligible and were divided into training (n=488) and validation (n=123) cohorts. Predictors included in the nomograms for total population were total dose, age, fibrinogen, prothrombin time (PT), comorbidity and concomitant use of voriconazole. Total dose, fibrinogen, PT, activated partial thromboplastin time (APTT), white blood cell and concomitant use of voriconazole were selected to predict hypofibrinogenemia for patients with malignant hematologic diseases. Both models were adequately calibrated and their predictions correlated with the observed outcome. The cut-off of treatment durations in total population and subgroup were 10 and 6 days, respectively. Tigecycline in combination with voriconazole could increase the risk of hypofibrinogenemia and tigecycline-induced hypofibrinogenemia is more likely to occur in patients with malignant hematologic diseases.