A Link Between Cytotoxicity in Cell Culture and Gastrointestinal Side Effects of Oral Anticoagulants: Bench-To-Bedside

Abstract

OBJECTIVE: Warfarin and nonvitamin-K oral anticoagulants including dabigatran, rivaroxaban, and apixaban are commonly used in the prophylaxis and treatment of systemic embolism and deep vein thrombosis. In this study, we aimed to compare the cytotoxic effects of warfarin and new oral anticoagulants and to show a possible correlation between cell cytotoxicity and gastrointestinal side effects in the real-life setting. METHODS: L929 cells were incubated with test materials. At 24 and 48 hours, morphological changes and cell viability were evaluated. RESULTS: At 24 and 48 hours, dabigatran resulted in altered cell morphology in all dilutions, while rivaroxaban, apixaban, and warfarin showed similar morphology with the control group, except for dilution I. Dabigatran and warfarin at 24 hours and at 48 hours had a statistically significantly lower cell viability in all dilutions, compared to the control group. CONCLUSION: Gastrointestinal side effect profiles of these four agents in a real-life setting is consistent with the results obtained from the present study. There is no sole factor with the potential of explaining the entire gastrointestinal side effect profiles of anticoagulant agents. However, direct cytotoxic effects of anticoagulants should be considered primarily for gastrointestinal side effects in accordance with the results of present head-to-head cytotoxicity study (Tab. 5, Fig. 3, Ref. 28). Text in PDF www.elis.sk.