Recurrent splenic infarction in triple-positive antiphospholipid syndrome despite therapeutic anticoagulation

Abstract Introduction: Splenic infarction is an uncommon condition often linked to autoimmune or inflammatory diseases. Its causes are broadly categorized as embolic or non-embolic, with embolic events being more common. Embolic infarctions are typically due to atrial fibrillation, cardiac procedures, endocarditis, or valvular disorders. Non-embolic causes are rarer and include autoimmune disorders (e.g., lupus, vasculitis) and hypercoagulable states such as male or antiphospholipid syndrome (APS). APS is a systemic autoimmune disease with diverse presentations. Diagnosis requires at least one clinical criteria–vascular thrombosis or pregnancy morbidity–along with persistent antiphospholipid antibodies (aPL): lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-B2 glycoprotein-I (anti-β2GPI) antibodies. Triple-positive APS, defined by the presence of all three antibodies, carries a higher risk for thrombosis, catastrophic APS, and adverse pregnancy outcomes. Although APS commonly presents with thromboembolism or obstetric complications, splenic infarction as an initial manifestation is rare. Case description: A 59-year-old woman presented with sharp left upper quadrant abdominal pain for five days that radiated to the chest and worsened with deep inspiration. Her medical history was notable for smoking and paroxysmal atrial fibrillation. She was normothermic and hemodynamically stable. Initial lab work was significant for normocytic anemia with hemoglobin of 11.5 g/dL. CT of the abdominal and pelvis with contrast revealed splenomegaly with peripheral wedge shaped hypoattenuation, consistent with splenic infarcts, and diffuse hepatic steatosis. CTA confirmed infarcts at the superior and inferior splenic margins without evidence of aneurysm, dissection, or stenosis. She was discharged on Apixaban. Hypercoagulable testing revealed positive LA, aCL, and anti-β2GPI antibodies, confirming triple-positive APS. Therefore, she was transitioned to warfarin. Three months later, she was readmitted with abdominal pain. Despite INR of 3, repeat CTA demonstrated increasing splenomegaly, confluent infarcts, and a patent splenic artery. Given progression despite therapeutic INR and high thrombosis risk from triple-positive APS, the patient was switched to Enoxaparin and aspirin 81 mg daily. Discussion: APS is an autoimmune, inflammatory disorder associated with the hypercoagulable state and tendency for recurrent arterial and venous thrombosis, thromboembolism, obstetric complications, and elevated antiphospholipid antibodies. Deep vein thrombosis is the most common initial presentation, occurring in approximately 39% of cases. Ischemic cerebrovascular events and thrombocytopenia occur in about 30%, while fetal loss affects nearly 50% of pregnant patients with APS (Azanero-Haro et al 2024). Though less common, thrombosis may involve organs such as the liver, kidneys, glands, heart, or spleen. Infarction is typically associated with cardiac thromboembolism, systemic disease, sickle cell trait, or infection. However, splenic infarction as an initial thrombotic manifestation of APS is rare, and its incidence is not well established. Warfarin remains the standard treatment for thrombotic APS, including triple-positive cases. However, warfarin resistance is reported more frequently among triple-positive patients, complicating anticoagulation management. In this case, the patient's evolving splenic infarcts, difficulty maintaining a therapeutic INR (target 2.5-3.5), and suspected warfare resistance prompted transition to weight-based subcutaneous Enoxaparin (1 mg/kg) with low-dose aspirin (81 mg daily). Conclusion: This case highlights the rarity of splenic infarction as an initial presentation of triple-positive APS. Although APS is commonly associated with thromboembolic events, splenic involvement is unusual and maybe easily overlooked. The patient's progression of infarcts, despite a therapeutic INR raised concern for possible warfarin resistance, a rare but important consideration in triple-positive APS. Ultimately transitioning to weight-based Enoxaparin with low-dose aspirin proved to be an effective alternative, emphasizing the need for personalized anticoagulation strategies in patients with high-risk APS who do not respond to standard therapy.