Introduction

Warm autoimmune hemolytic anemia (wAIHA) is the most common subtype of autoimmune hemolytic anemia and is characterized by immunoglobulin G (IgG)-mediated destruction of erythrocytes at body temperature, resulting primarily in Fc receptor-mediated extravascular hemolysis within the spleen [1]. Although uncommon, with an estimated annual incidence of one to three cases per 100,000 individuals, wAIHA remains an important cause of acquired hemolytic anemia because of its potential for rapid clinical deterioration and significant morbidity and mortality [2,3]. Clinical presentation ranges from compensated chronic hemolysis to fulminant anemia associated with hemodynamic instability, tissue hypoxia, and multiorgan dysfunction requiring urgent transfusion and immunosuppressive therapy [1-3].

Approximately one-half of all cases of wAIHA are secondary to an underlying disorder, including lymphoproliferative malignancies, autoimmune diseases, infections, medications, immunodeficiency syndromes, and, less commonly, solid organ malignancies [1,3]. Among autoimmune diseases, systemic lupus erythematosus (SLE) represents one of the most well-recognized causes of secondary wAIHA, whereas Sjögren syndrome is a considerably less common but increasingly recognized association [4-6]. Hematologic abnormalities are common manifestations of systemic autoimmunity and include autoimmune hemolytic anemia, immune thrombocytopenia, leukopenia, neutropenia, and pancytopenia. Importantly, these cytopenias may precede the development of classic rheumatologic manifestations, making autoimmune hemolytic anemia the presenting feature of an evolving systemic autoimmune disorder [4,6].

Patients with overlapping autoimmune diseases, including SLE, Sjögren syndrome, and autoimmune thyroid disease, demonstrate profound immune dysregulation characterized by chronic B-cell activation, autoreactive T-cell responses, complement activation, and production of multiple pathogenic autoantibodies [5,6]. This phenomenon, commonly referred to as polyautoimmunity, increases susceptibility to immune-mediated cytopenias while often complicating diagnosis and management. Distinguishing isolated autoimmune hemolytic anemia from autoimmune overlap syndromes or disorders such as Evans syndrome may therefore be challenging, particularly in patients presenting with thrombocytopenia or multiple positive autoimmune serologies.

The diagnosis of wAIHA relies on both clinical suspicion and laboratory evidence of hemolysis. Typical findings include elevated lactate dehydrogenase, indirect hyperbilirubinemia, reticulocytosis, decreased or undetectable haptoglobin, and spherocytes on peripheral blood smear. Confirmation is obtained through a positive direct antiglobulin test (DAT) demonstrating IgG with or without complement (C3) coating erythrocytes [1]. Patients with complement-positive wAIHA may experience more severe hemolysis because both splenic macrophage-mediated erythrophagocytosis and complement activation contribute to erythrocyte destruction. Severe disease frequently complicates blood bank compatibility testing because warm autoantibodies react broadly with donor erythrocytes, making identification of completely compatible blood difficult. Nevertheless, transfusion should not be delayed in patients with life-threatening anemia, as timely restoration of oxygen-carrying capacity outweighs concerns regarding serologic incompatibility [1,7].

Corticosteroids remain the cornerstone of first-line treatment and achieve initial response rates approaching 70-85% by reducing macrophage-mediated erythrophagocytosis and suppressing autoantibody production [1]. Patients with fulminant hemolysis frequently require escalation of therapy with pulse-dose intravenous corticosteroids, intravenous immunoglobulin (IVIG), and judicious transfusion support guided by clinical status while definitive immunosuppressive therapy takes effect. Rituximab has become the preferred second-line treatment for steroid-refractory or relapsed disease, demonstrating durable remission rates and reducing the need for splenectomy [2,8]. Because management often requires simultaneous treatment of hemolysis, transfusion support, and the underlying autoimmune disease, multidisciplinary collaboration among hematology, rheumatology, transfusion medicine, and internal medicine is essential for optimizing outcomes.

Profound anemia resulting from wAIHA remains uncommon, and reports describing hemoglobin concentrations approaching 3 g/dL are limited. Such presentations represent true hematologic emergencies requiring immediate recognition and coordinated multidisciplinary intervention. Furthermore, cases occurring in the setting of autoimmune overlap syndromes involving reported Sjögren syndrome with evolving SLE remain rare and provide valuable insight into the complex relationship between systemic autoimmunity and immune-mediated cytopenias.

We present the case of a young woman with reported Sjögren syndrome and clinical and serologic features concerning evolving SLE who developed fulminant wAIHA with a hemoglobin nadir of 3.2 g/dL despite multiple packed red blood cell (PRBC) transfusions. Prompt treatment with pulse-dose intravenous methylprednisolone, IVIG, and supportive transfusion therapy resulted in complete hematologic recovery without the need for rituximab or splenectomy. This case highlights the importance of recognizing severe autoimmune hemolytic anemia as a potentially life-threatening manifestation of systemic autoimmunity, emphasizes the diagnostic challenges posed by autoimmune overlap syndromes, and demonstrates that timely, aggressive first-line immunosuppressive therapy can achieve excellent outcomes even in patients presenting with profound anemia.