Case Report: Direct Oral Anticoagulants Treatment Failure for Venous Thromboembolism in the Setting of Multiple Thrombophilic Conditions

This case report describes the treatment failure of two direct oral anticoagulants (DOACs) in a patient with multiple thrombophilic conditions, including triple-positive antiphospholipid syndrome (APS) and heterozygous Factor V Leiden mutation. A 69-year-old male with a history of recurrent venous thromboembolism developed a deep vein thrombosis while receiving rivaroxaban, followed by an acute ischemic stroke while on dabigatran. Due to recurrent thrombosis despite therapeutic DOAC therapy, the patient was transitioned to warfarin with low-molecular-weight heparin bridging. After achieving a therapeutic INR, the patient remained stable without further thromboembolic or bleeding events during follow-up in a pharmacist-managed anticoagulation clinic.Current guidelines, including the 2020 ISTH Scientific and Standardization Committee guidance, recommend vitamin K antagonists over DOACs in high-risk APS, particularly in patients with triple-positive antibodies, due to the increased risk of recurrent thrombosis with DOAC therapy. This recommendation is supported by the TRAPS trial, which demonstrated a significantly higher rate of thromboembolic events with rivaroxaban compared to warfarin in triple-positive APS patients.This case supports existing guideline recommendations and highlights the limitations of targeted anticoagulation, including both factor Xa inhibitors and direct thrombin inhibitors, in patients with complex thrombophilia. In patients with high-risk APS or multiple thrombophilic conditions, warfarin has been shown to be more reliable anticoagulation compared with DOACs. The sequential failure of two mechanistically distinct DOACs in this case further underscores the importance of guideline-concordant anticoagulant selection and the role of pharmacists in identifying high-risk patients at the point of prescribing and dispensing.