When Warm Meets Cold: Mixed-Type Autoimmune Hemolytic Anemia Revealing an Underlying Autoimmune Disorder

Autoimmune hemolytic anemia (AIHA) is a rare immune-mediated disorder caused by autoantibodies directed against red blood cell antigens. Mixed-type AIHA, characterized by the coexistence of warm-reactive IgG and cold-reactive complement-fixing antibodies, is uncommon and often diagnostically challenging due to overlapping serologic features and transfusion incompatibility. We report the case of a 40-year-old woman who presented with an acute onset of breathlessness, palpitations, and severe fatigability. She was found to have severe anemia (hemoglobin 2.7 g/dL), reticulocytosis, indirect hyperbilirubinemia, and red cell agglutination on peripheral smear. Both direct and indirect Coombs tests were strongly positive, while antibody screening demonstrated panreactivity with positive autocontrol. The monospecific direct antiglobulin test confirmed positivity for IgG and C3d, establishing the diagnosis of mixed-type AIHA. In view of hemodynamic instability, transfusion with the least-incompatible packed red cells was performed under warming precautions, alongside high-dose intravenous corticosteroids. The patient improved symptomatically, with hemoglobin rising to 8.8 g/dL. Autoimmune workup revealed high-titer antinuclear antibody and anti-SSA positivity, suggesting an evolving systemic autoimmune disorder. Mixed-type AIHA accounts for less than 10% of cases but is associated with significant morbidity due to combined extravascular and complement-mediated hemolysis, often necessitating cautious transfusion of least-incompatible blood in life-threatening anemia and escalation to rituximab or other immunosuppressive agents. This case highlights the diagnostic complexity, therapeutic challenges, and need for long-term autoimmune surveillance in patients with mixed-type AIHA.