Blood: Potential Mechanisms of Drug Induced Bleeding

Drug-induced bleeding leads to higher morbidity and mortalityAntithrombotic drugs, which have obvious causes for accidental bleeding, are relatively easy to controlBut the mechanism of bleeding disorders caused by most drugs is unclear, which makes intervention more difficultBecause most bleeding abnormalities are associated with dysfunction of coagulation factors, Chen et alused their recently established cell-based analytical methods to identify drugs that may have off-target effects that affect the biosynthesis of active vitamin L-dependent (VKD) coagulationthe study screened 727 drugs in the NIH Clinical Inclusion (NCC) library and identified 9, including the most commonly prescribed anticoagulant warfarinBleeding complications associated with these drugs have been clinically reported, but the pathogenesis is not clearFurther representation of VKD degeneration inhibitory effects of 9 commonly used drugsshowed that warfarin, lansorafen, nitrosamine were mainly targeted at vitamin K epoxy reductase (VKOR), while Adipone, chlorofazim, and AM404 mainly worked on vitamin K reductase (VKR) in the vitamin K oxidizing cyclethe other three drugs mainly affect the effectiveness of vitamin K in cellsThe molecular mechanism of VKOR and VKR inactivation is expoundedStudies based on cell and animal models show that anticoagulant effects of drugs targeting VKOR instead of VKR can be saved by taking vitamin Kthis study provides insights into the prevention and management of drug-induced haemorrhagic diseasesEstablished cell-based high-throughput screening methods provide a powerful tool for screening new vitamin K antagonists with anticoagulant