Exploratory Untargeted Plasma Lipidomics Suggests Subtype-Associated Lipid Alterations in Hereditary Hemolytic Anemias

Background/Objectives: Hereditary hemolytic anemias (HHAs) are rare genetic disorders characterized by chronic hemolysis, systemic oxidative stress, and inflammation. Altered lipid homeostasis has previously been reported in HHAs; however, untargeted plasma lipidomic studies comparing HHA subtypes remain limited. This exploratory study aimed to characterize shared and subtype-specific plasma lipid alterations across five HHA subtypes.

Methods

Forty-eight participants were enrolled, including 29 patients with HHA (6 with β-thalassemia, 5 with hereditary xerocytosis, 7 with hereditary spherocytosis, 5 with sickle cell disease, and 6 with congenital dyserythropoietic anemia) and 19 healthy controls. Plasma lipids were analyzed by untargeted liquid chromatography–quadrupole time-of-flight mass spectrometry, followed by multivariate, univariate, and lipid pathway analyses.