B53-10 Fatal Catastrophic Seronegative Antiphospholipid Syndrome Overlapping With Anca-associated Vasculitis

Introduction Antiphospholipid syndrome (APS) is classically defined by thrombosis in the presence of antiphospholipid antibodies (aPL). Seronegative APS is increasingly recognized as a phenotype in which clinical thrombotic behavior is indistinguishable from APS despite persistently negative standard aPL assays. Diagnostic anchoring on laboratory criteria can delay recognition. Here, we present a fulminant case where catastrophic seronegative APS coexisted with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, resulting in fatal multisystem ischemia despite aggressive immunosuppression and anticoagulation. Case Presentation A healthy 36-year-old woman, with no chronic medical illnesses but with a history of a prior unexplained first-trimester pregnancy loss, presented with acute-onset dysarthria and left-sided weakness. Imaging demonstrated right frontal hypoperfusion, but she was outside the window for thrombolytics. Within 24 hours she deteriorated with shock and respiratory failure requiring the intensive care unit (ICU). She had severe anemia, thrombocytopenia, acute kidney injury (creatinine 2.2 mg/dL), hypoalbuminemia, and markedly elevated inflammatory markers. Computed tomography (CT) imaging demonstrated diffuse anasarca, hepatic steatosis, and moderate ascites. Echocardiography showed aortic valve thickening concerning for Libman-Sacks endocarditis. Autoimmune studies showed high PR3 IgG (239 U), ANCA titer 1:640, and antinuclear antibody (ANA) 1:2560, consistent with ANCA-associated vasculitis. However, antiphospholipid antibodies were negative. Given the extent and pattern of thrombosis, seronegative APS overlap was considered. She received pulse-dose corticosteroids, eculizumab, intravenous immunoglobulin (IVIG), and rituximab. Hospital course was complicated by hyperammonemia, recurrent ileus, ischemic digital necrosis, gastrointestinal (GI) bleeding from coagulopathy, and mechanical ventilation requiring tracheostomy. She later underwent emergent laparotomy for perforated distal transverse colon with segmental resection and end colostomy. Multiple ischemic territories (stroke, peripheral tissue necrosis, mesenteric ischemia, and suspected Libman-Sacks endocarditis) were attributed to a catastrophic thrombo-inflammatory state. Anticoagulation was resumed once stable. Days later she developed hemorrhagic shock with evolving disseminated intravascular coagulation (DIC). Given ongoing thrombotic injury, inability to maintain anticoagulation, and multisystem organ failure, care was transitioned to comfort-focused goals. She died on hospital day 29. Discussion This case demonstrates that seronegative APS can produce catastrophic ischemia indistinguishable from classic APS, and ANCA vasculitis can coexist as a second autoimmune accelerator. Reliance on negative aPL serologies can mislead clinicians away from APS when escalation of immunomodulation is needed. When thrombosis is widespread and multiterritorial, especially in a patient with concurrent systemic autoimmunity, seronegative APS must remain on the differential. Recognition must be based on phenotype—not the antibody panel alone. This abstract is funded by: None