: A case report of a patient with antiphospholipid syndrome (APS) with positive lupus anticoagulant and a mechanical mitral valve replacement (MVR) who presented with a thrombosis and difficult-to-control INRs. Current literature on anticoagulation options for patients who present with these conditions as well as alternate laboratory assays are reviewed. APS can present a unique complexity and challenge to appropriate anticoagulation on warfarin. Although there are emerging data regarding the use of novel oral anticoagulants to treat this condition, they do not justify their use in a patient with APS and an MVR because of a current lack of evidence. CFX testing may be used to calibrate INRs when there is a concern for false readings because of lupus anticoagulant interaction with INR assays.