A case of mesalamine potentiating hypoprothrombinemic effect of vitamin K antagonist (VKA) therapy resulting in life-threatening bleeding

A 76-year-old male patient, who underwent a post-aortic valve replacement with a mechanical valve in 2006, was on oral anticoagulant therapy with warfarin, maintaining a stable therapeutic level of anticoagulation until 2022. He had a new diagnosis of ulcerative colitis in 2022, following which he was started on mesalamine. He had been having a supratherapeutic level of anticoagulation, as evidenced by an international normalized ratio (INR) of 12 to 14 on multiple occasions since 2022, leading to gastrointestinal bleeding, necessitating multiple packed red cell transfusions. He presented to us in August 2024 with severe anemia due to gastrointestinal bleeding. The evaluation revealed severe depletion of vitamin K-dependent coagulation factors. In this report, we discuss the possible drug-drug interactions between mesalamine and vitamin K antagonists, which went unrecognized leading to life-threatening gastrointestinal bleeding.