From warfarin resistance to warfarin overdose: an unusual case report

Warfarin resistance represents a rare yet clinically significant challenge, especially among patients with mechanical heart valves. It may result from either hereditary or acquired factors.

A 27-year-old male patient with a history of aortic and mitral valve replacement was followed with subtherapeutic International Normalized Ratio (INR) of 1.8-2.0 despite receiving 20 mg/day of warfarin. He was hospitalized for evaluation, and potential acquired causes of warfarin resistance were excluded. The patient was discharged with a plan for close INR monitoring. Following the initiation of lorazepam and olanzapine for a comorbid psychiatric condition, he re-presented with bleeding manifestations due to warfarin overdose. Notably, his apparent warfarin resistance resolved after the addition of these medications, and he has since been maintained within the therapeutic INR range on a stable warfarin dose of 5 mg/day.

Warfarin is known to interact with numerous medications, and new drug interactions continue to be reported in the literature. Although no major interactions with lorazepam or olanzapine have been previously documented, in this case the concomitant initiation of these agents appeared to overcome warfarin resistance. This clinical course was remarkable for the apparent resolution of warfarin resistance, raising the possibility of underlying pharmacologic interactions.