Zebra of the Week: Warm autoimmune hemolytic anemia

Warm autoimmune hemolytic anemia (wAIHA) is the most common form of autoimmune hemolytic anemia, but it remains a rare disorder that many clinicians encounter only infrequently in practice. The condition is characterized by the production of autoantibodies, typically immunoglobulin G (IgG), that bind to red blood cells (RBCs) at normal body temperatures. The resulting immune-mediated destruction of RBCs leads to hemolytic anemia, with hemolysis occurring primarily in the spleen.

Clinical presentation is often driven by the severity and tempo of anemia. Common symptoms include fatigue, weakness, dyspnea, jaundice, and dark urine. Patients may also report palpitations, dizziness, or exercise intolerance. In more severe cases, chest pain, syncope, fever, or heart failure can occur. Because extravascular hemolysis is concentrated in the spleen, mild splenomegaly is relatively common.

The disorder can develop at any age, although incidence increases with advancing age. wAIHA may occur as a primary condition or in association with other disorders, including lymphoproliferative diseases, autoimmune diseases, infections, or certain medications. Diagnosis typically relies on evidence of hemolysis, such as anemia with elevated LDH and indirect bilirubin levels, reduced haptoglobin, and reticulocytosis, along with a positive direct antiglobulin (Coombs) test.

Management has historically focused on suppressing the immune response and limiting RBC destruction. Corticosteroids have long been considered first-line therapy, while rituximab, splenectomy, and other immunosuppressive agents have been used for refractory or relapsing disease. However, treatment can be challenging, as many patients experience recurrent disease, require prolonged immunosuppression, or remain dependent on corticosteroids.

FDA approves first treatment specifically for wAIHA

In August 2026, FDA approved Imaavy (nipocalimab-aahu) for adults and adolescents aged 12 years and older with wAIHA who are currently or were previously treated with corticosteroids. According to the manufacturer, this is the first therapy specifically approved for wAIHA. Nipocalimab is a neonatal Fc receptor (FcRn) blocker designed to reduce circulating pathogenic IgG autoantibodies while preserving B-cell function.

Approval was based on the phase 2/3 ENERGY trial, in which patients receiving nipocalimab were more likely than those receiving placebo to achieve a durable hemoglobin response, with improvements in hemoglobin levels and fatigue measures. The approval introduces a targeted therapeutic option for a disease that has traditionally relied on broad immunosuppression.

Sources:

NIH GARD. Autoimmune Hemolytic Anemia, Warm Type

Johnson & Johnson. (2026 Aug 24) FDA Approves IMAAVY® (nipocalimab-aahu) as First-Ever Treatment for Warm Autoimmune Hemolytic Anemia (wAIHA), Representing a Landmark Advancement for Patients