Mechanism of abnormal coagulation induced by tigecycline in cancers

Tigecycline is a broad-spectrum active intravenous antibiotic that is also active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is not yet clear. In this study, we found tigecycline could cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT) and D-dimer. In addition, functional studies have found that tigecycline could inhibit platelet adhesion and aggregation, and the patient's coagulation function could gradually recover after discontinuation. Gene sequencing results suggested that tigecycline could significantly regulate the expression of genes related to platelet function pathways, and could increase the incidence of single nucleotide polymorphisms and the number of alternative splices in CHO cells with tigecycline treatment. Abnormal platelet function and low numbers are common in patients with hematological malignancies. Our study could explain the mechanism of abnormal coagulation caused by tigecycline. At the same time, a warning should be given when doctors applied tigecycline to cure infections in tumor patients. Overall design: The CHO cells treated with tigecycline (0 mg/ml and 0.2 mg/ml) for 48 h was used for RNA sequencing.