Beyond the Colon: Acute Hemolysis Associated With Etrasimod Therapy

Etrasimod is an oral sphingosine 1-phosphate (S1P) receptor modulator used in the treatment of moderately to severely active ulcerative colitis (UC). Although its safety profile has been described in clinical studies, hematologic complications remain incompletely characterized. We report the case of a 31-year-old man with well-controlled UC who developed acute hemolytic anemia approximately two months after initiation of etrasimod therapy. Evaluation revealed macrocytic anemia with marked reticulocytosis, schistocytes on peripheral smear, elevated ferritin, and a positive direct antiglobulin test (IgG-positive, complement-negative), consistent with immune-mediated hemolysis. Extensive evaluation excluded infectious, metabolic, and hereditary causes. Discontinuation of etrasimod and transfusion support resulted in incomplete improvement; subsequent high-dose corticosteroid therapy led to recovery of hemoglobin levels and resolution of hemolysis. To our knowledge, this is the first reported case of immune-mediated hemolytic anemia associated with etrasimod therapy. Awareness of this rare but potentially serious adverse event is important as the clinical use of S1P receptor modulators continues to expand.