Hydroxycarbamide-induced changes in E/beta thalassemia red blood cells.
In thalassemia, fetal hemoglobin (HbF) augmentation with hydroxycarbamide (also known as hydroxyurea) is not always successful. The expected parallel effects on red cell (RBC) membrane deformability, cell hydration, and membrane phospholipid organization, all important for extending RBC life span and increasing Hb, have been infrequently examined. We analyzed these characteristics in 15 nontransfused E/beta(0) thalassemia patients treated with HU (mean 10.2 months). Membrane deformability and cell hydration mildly improved in association with increased HbF levels approaching statistical significance (r = 0.51, P = 0.06). All measures improved considerably in splenctomized patients. These findings underscore the disappointing results of hydroxyurea treatment in clinical trials and the importance of examining the effect on RBC characteristics for the development and understanding of HbF-enhancing agents.
Singer
Sylvia T
ST
Hematology/Oncology Department and Clinical Research Center at Oakland, CA, USA. tsinger@mail.cho.org
Vichinsky
Elliott P
EP
Larkin
Sandra
S
Olivieri
Nancy
N
Sweeters
Nancy
N
Kuypers
Frans A
FA
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004909:Erythrocyte Indices; D005260:Female; D005319:Fetal Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006446:Hemoglobin E / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D009996:Osmotic Fragility / Q000187:drug effects; D017086:beta-Thalassemia / Q000188:drug therapy*
D019384:Nucleic Acid Synthesis Inhibitors; D006446:Hemoglobin E; D005319:Fetal Hemoglobin; D006918:Hydroxyurea