Nonbacterial thrombotic endocarditis (NBTE) is an uncommon condition that carries significant morbidity and an in-hospital mortality rate of up to 36%. Involvement of a prosthetic valve with NBTE is even more rare. We present a case of prosthetic mitral valve NBTE that manifested 5 months after surgical mitral valve replacement. The patient's presentation was complicated by complex medical comorbidities and previous contraindications to multiple anticoagulant agents that included calciphylaxis secondary to warfarin and high concern for heparin-induced thrombocytopenia. The patient was taking apixaban when she developed prosthetic valve NTBE. The patient was transitioned to fondaparinux, with resolution of the mitral valve vegetations. Warfarin and heparin are first-line anticoagulant agents for antiphospholipid syndrome and NBTE, respectively. There is limited evidence for different anticoagulant agents in NBTE. Our case highlights nuance in the diagnosis of NBTE and complexities of anticoagulation decisions in patients with contraindications to various agents.

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