Severe Warm Autoimmune Hemolytic Anemia With Profound Anemia Requiring Multimodal Immunosuppressive Therapy

Warm autoimmune hemolytic anemia (wAIHA) is an uncommon but potentially life-threatening autoimmune disorder characterized by immunoglobulin G (IgG)-mediated destruction of erythrocytes. Secondary wAIHA frequently occurs in association with systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE), while Sjögren syndrome represents a less common but recognized association. Fulminant presentations with profound anemia remain rare and require prompt diagnosis, aggressive immunosuppressive therapy, and multidisciplinary management. We present the case of a 25-year-old woman with a history of reported Sjögren syndrome, Hashimoto thyroiditis, and clinical and serologic features concerning for evolving SLE who developed rapidly progressive direct antiglobulin test (DAT)-positive wAIHA. Despite receiving five units of packed red blood cells (PRBCs) at an outside hospital, her hemoglobin continued to decline after transfer, reaching a nadir of 3.2 g/dL. Laboratory evaluation demonstrated marked hemolysis with reticulocytosis, elevated lactate dehydrogenase, indirect hyperbilirubinemia, undetectable haptoglobin, spherocytes on peripheral smear, and a DAT positive for both IgG and complement (C3). The hospital course was further complicated by thrombocytopenia and severe splenomegaly, raising concern for autoimmune overlap syndrome and possible Evans syndrome. She was successfully treated with pulse-dose intravenous methylprednisolone, intravenous immunoglobulin (IVIG), folic acid supplementation, and transfusion support. Rheumatologic evaluation revealed positive antinuclear antibody (ANA), anti-SSA, antiphospholipid, and anti-thyroid peroxidase antibodies, prompting initiation of hydroxychloroquine. Hemolysis resolved rapidly with normalization of bilirubin, recovery of platelet count, and sustained improvement in hemoglobin, allowing transition to an oral prednisone taper without requiring rituximab or splenectomy. This case highlights that wAIHA may represent the initial manifestation of evolving systemic autoimmune disease and should be considered in young patients presenting with profound hemolytic anemia. Early recognition, aggressive first-line immunosuppressive therapy, timely transfusion support, and multidisciplinary collaboration can be lifesaving and may achieve complete hematologic recovery without the need for second-line biologic therapy.