Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder that often affects young women. It is recognized by the presence of antiphospholipid antibodies, including anticardiolipin antibodies (aCL), lupus anticoagulant (LA), and anti-beta-2-glycoprotein I (aβ2GPI) antibodies in the setting of venous or arterial thrombosis or pregnancy morbidity. APS can be primary or secondary to autoimmune diseases, drugs, infections, or malignancy. Clinicians should maintain a high index of suspicion for secondary APS, especially in older patients or those with progressive thrombosis despite adequate anticoagulation. This report presents an anticoagulant-refractory case of APS in a 60-year-old woman that was ultimately driven by an underlying lymphoproliferative disorder. Case Presentation A 60-year-old woman with hypertension, atrial fibrillation, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), gout, gastroesophageal reflux disease (GERD), and fatty liver disease presented with left upper quadrant abdominal pain associated with nausea, vomiting, and early satiety. A computerized tomography (CT) scan revealed splenomegaly with splenic infarcts. Coagulation studies showed a normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and mild thrombocytopenia. The mixing study demonstrated persistently elevated aPTT. Complete blood count showed anemia and leukopenia. Haptoglobin was low, complement level was normal, and antinuclear antibody (ANA) was elevated. Autoimmune serology confirmed persistently elevated aCL, elevated aβ2GPI antibody, and LA. Since diagnosis, her course was marked by failure to respond to a direct oral anticoagulant and subsequently to warfarin, as evidenced by progressive splenomegaly and the appearance of new splenic infarcts. She was therefore transitioned to subcutaneous enoxaparin, but her symptoms did not improve. Repeat imaging showed a new enhancing right lower mesenteric mass of unclear etiology. Peripheral blood smear showed relative lymphocytosis, although the morphology was not diagnostic for chronic lymphocytic leukemia. Flow cytometry demonstrated involvement by a CD5-negative, CD10-negative kappa-restricted B-cell lymphoproliferative disorder. Bone marrow biopsy confirmed a monotypic CD5-negative, CD10-negative B-cell population most consistent with splenic marginal zone lymphoma. Discussion Late-onset APS that continues to cause recurrent arterial and venous thrombosis with organ infarction despite appropriate anticoagulation should raise suspicion for a secondary driver, including a paraneoplastic process. In this patient, the refractory thrombotic behavior was related to an underlying lymphoproliferative disorder. Adequate anticoagulation could not be achieved without addressing the driving malignancy. She was started on rituximab 375 mg/m² intravenously (IV) weekly in addition to therapeutic enoxaparin 80 mg subcutaneously twice daily and aspirin 81 mg daily, resulting in clinical improvement. This abstract is funded by: None
Alhroob et al. (Fri,) studied this question.