Warfarin-induced calciphylaxis-related skin ulceration in patients with end-stage renal disease: case report and literature review

Abstract

Calciphylaxis is a rare but highly disabling disease, occurring both in chronic kidney disease (CKD) with renal replacement therapy (RRT) and in normal renal function. Given the frequent coexistence of atrial fibrillation (AF) and CKD, anticoagulation is often required. Warfarin, as a promoter of vascular calcification, is frequently reported as a triggering factor of calciphylaxis. Here, we present the case of a 71-year old male patient with a history of AF and a previous ischaemic stroke, on RRT for three years and warfarin therapy. The patient presented with two painful necrotic skin ulcers over the right leg and a skin biopsy confirmed calciphylaxis. After discontinuation of warfarin, the lesions completely healed with sodium thiosulfate intravenous infusion and local wound treatment. A literature search was performed up to 1 September 2022 through PubMed. The following terms were searched in different combinations: ‘calciphylaxis’; ‘VKA’ [vitamin K antagonist]; ‘warfarin’; ‘haemodialysis’; ‘end-stage renal disease’; and ‘ulcer’. In our opinion, in patients requiring anticoagulant therapy, the introduction or continuation of vitamin K antagonists (VKAs) should be carefully balanced when calciphylaxis develops, and other options, such as enoxaparin or apixaban, should be considered. Clinical decisions for patients requiring haemodialysis and requiring anticoagulant therapy should take into account the possible risk of warfarin-induced calciphylaxis. Further studies are needed to clarify the safety, tolerability profile and outcomes of each currently available treatment in this patient population.