Prolongation of prothrombin time-international normalized ratio by concomitant use of warfarin and combination therapy with lenvatinib and pembrolizumab in a patient with renal cell carcinoma on dialysis: a case report

Abstract Background Acquired polycystic kidney disease is associated with an increased risk of developing renal cell carcinoma (RCC), which is commonly observed in patients on dialysis and may present with inferior vena cava tumor thrombus. However, there are no prior reports on the use of warfarin for inferior vena cava tumor thrombus in patients on dialysis with RCC receiving combination therapy with lenvatinib and pembrolizumab. Case presentation We describe a 64-year-old Japanese man with RCC complicated by tumor thrombus extending into the renal vein and inferior vena cava who was undergoing hemodialysis. Warfarin was initiated at 2 mg/day due to the risk of thrombus progression. His baseline prothrombin time-international normalized ratio (PT-INR) was 1.80 before the initiation of combination therapy with lenvatinib and pembrolizumab. After 8 days of warfarin administration, combination therapy with lenvatinib (10 mg/day) and pembrolizumab (200 mg every 3 weeks) was initiated. Nine days later, the PT-INR elevated to 3.02 despite no change in warfarin dose. The patient remained asymptomatic. Adjusting warfarin to 2–2.5 mg/day and close PT-INR monitoring successfully restored values to the therapeutic range of 1.6–2.6 by day 80, without reducing the lenvatinib dose. Conclusions Neither warfarin nor lenvatinib is eliminated by dialysis; therefore, potential pharmacokinetic interactions should be managed with the same caution as in non-dialysis patients. Concomitant use of warfarin and combination therapy with lenvatinib and pembrolizumab in patients with RCC undergoing hemodialysis may enhance anticoagulant effects via multiple interacting factors, including cytochrome P-450-related interactions, systemic inflammation, and hypoalbuminemia. Therefore, careful follow-up, including shorter intervals between outpatient visits (e.g., weekly monitoring), is essential for safe PT-INR management.