Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report

Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 10<sup>9</sup>/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.