Rivaroxaban therapy failed in a 42-year-old man with complex thrombophilia, leading to recurrent deep vein thromboses and chronic thromboembolic pulmonary hypertension requiring surgical embolectomy.
Case Report (n=1)
DOAC therapy may fail in patients with complex thrombophilia, such as antiphospholipid antibodies and protein C deficiency, leading to recurrent VTE and CTEPH.
Abstract Background Direct oral anticoagulants (DOACs) have become the preferred therapy for venous thromboembolism (VTE) due to their efficacy, reduced bleeding risk, and simplified dosing compared to vitamin K antagonists (VKAs). However, true DOAC treatment failure—defined as recurrent or progressing thrombosis despite medication adherence—remains poorly characterized. Chronic thromboembolic pulmonary hypertension (CTEPH) represents a severe consequence of unresolved pulmonary embolism (PE) and progressive pulmonary vascular remodeling. We present a case of CTEPH in a patient with documented DOAC adherence, highlighting challenges in recognizing and managing anticoagulation failure. Case A 42-year-old man with morbid obesity, multiple prior deep vein thromboses (DVTs), and an unprovoked submassive bilateral PE was started on rivaroxaban (20 mg daily). Hypercoagulable testing revealed protein C deficiency and positive anticardiolipin antibodies, and lifelong anticoagulation was advised. One month later, he presented with worsening dyspnea and orthopnea. Computed tomography angiography (CTA) demonstrated persistent bilateral emboli with right ventricular (RV) strain. The patient was discharged home with the recommendation to continue taking rivaroxaban. Despite strict adherence, he again presented ten months later with progressive exertional dyspnea. Repeat CTA revealed unchanged segmental pulmonary emboli with new main pulmonary artery dilation. Lower-extremity ultrasound identified new left femoral and popliteal DVTs, confirming recurrent VTE despite therapy. Echocardiography revealed severe RV systolic dysfunction, and ventilation-perfusion (V/Q) scanning demonstrated multiple mismatched perfusion defects consistent with CTEPH. DOAC failure was diagnosed, and the patient was started on lovenox and bridged to warfarin. Due to worsening pulmonary hypertension and right heart failure, he underwent surgical pulmonary embolectomy, with subsequent clinical improvement. Discussion This case highlights the potential for DOAC failure in patients with complex thrombophilia. Underlying conditions such as antiphospholipid antibody positivity and protein C deficiency may impair the efficacy of factor Xa inhibition, predisposing to recurrent thromboembolism. The absence of routine monitoring can obscure subtherapeutic anticoagulation, especially in high-risk individuals. Selective use of anti-factor Xa level testing may aid in identifying inadequate exposure. Moreover, early recognition of chronic thromboembolic disease and timely referral for thrombectomy—before progression to right heart failure—can improve outcomes. Further investigation is warranted to establish criteria for DOAC failure and guide conversion to VKAs or surgical intervention. This abstract is funded by: None
Szasz et al. (Fri,) conducted a case report in Recurrent Thrombosis and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (n=1). Rivaroxaban was evaluated on DOAC treatment failure (recurrent or progressing thrombosis despite medication adherence). Rivaroxaban therapy failed in a 42-year-old man with complex thrombophilia, leading to recurrent deep vein thromboses and chronic thromboembolic pulmonary hypertension requiring surgical embolectomy.