Mixed-Pattern Autoimmune Hemolytic Anemia with Multi-Organ Failure Temporally Associated with Semaglutide Initiation: A Case Report

Authors

• Samuel R. Briggs, Department of Medicine, MaineHealth Maine Medical Center, Portland, MaineFollow
• David Rabinovich, Department of Medicine, MaineHealth Maine Medical Center, Portland, Maine
• Vatche Tchekmedyian, Department of Medicine, MaineHealth Maine Medical Center, Portland, Maine

Submission Type

Case Report

Abstract

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare but potentially fatal disorder mediated by autoantibodies against red blood cell antigens. Drug-induced immune hemolytic anemia is a recognized, though uncommon, etiology that is historically associated with antimicrobials and chemotherapeutics. Glucagon-like peptide-1 receptor agonists have not previously been implicated in immune hemolysis.
Clinical Findings: A 53-year-old woman with obesity presented with syncope, dyspnea, abdominal pain, and jaundice 17 days after initiating semaglutide. Her hematocrit was 11%; hemoglobin, lactate dehydrogenase, bilirubin, and transaminases were unmeasurable due to severe hemolysis. Leukocytosis (39.6 × 10⁹/L), thrombocytopenia (100 × 10⁹/L), acute kidney injury, and shock liver were present. Peripheral smear showed red cell agglutination, spherocytosis, reticulocytosis, and nucleated red blood cells. Direct antiglobulin testing (DAT) was positive for immunoglobulin G and C3d; the eluate was negative on 2 occasions.
Clinical Course: Treatment required emergent transfusion, high-dose intravenous methylprednisolone, plasma exchange, intravenous immunoglobulin, rituximab, and eculizumab. Acute kidney injury progressed to anuria that required hemodialysis for 1 month. Infectious, autoimmune, and lymphoproliferative workup was unrevealing. The DAT results normalized within 6 weeks of semaglutide discontinuation. Hemoglobin, renal function, and hepatic enzymes normalized by 4 months. The patient continued to have normal blood counts without any evidence of hemolysis at 1 year.
Conclusions: This case describes life-threatening AIHA with multi-organ failure temporally associated with semaglutide. The negative eluate and rapid DAT result normalization after drug discontinuation are consistent with drug-induced immune hemolytic anemia. Clinicians should consider drug-induced etiologies in new AIHA presentations, particularly with recently initiated agents.

Recommended Citation

Briggs, Samuel R.; Rabinovich, David; and Tchekmedyian, Vatche (2026) "Mixed-Pattern Autoimmune Hemolytic Anemia with Multi-Organ Failure Temporally Associated with Semaglutide Initiation: A Case Report," Journal of Maine Medical Center: Vol. 8 : Iss. 2 , Article 7.
Available at: https://doi.org/10.46804/2641-2225.1265