Document Detail


Effects of hydroxyurea on hemoglobin F and water content in the red blood cells of dogs and of patients with sickle cell anemia.
MedLine Citation:
PMID:  1712641     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A rationale for clinical trials of hydroxyurea (HU) treatment in sickle cell disease is that the agent increases red blood cell (RBC) fetal hemoglobin content. However, an additional effect of HU is to raise the mean corpuscular volume (MCV). To investigate the action of HU in a species that makes no electrophoretically distinguishable fetal hemoglobin, we treated dogs with the drug and compared their response to that of five patients with sickle cell anemia. Both dogs and patients had an increase in MCV, but the effect of HU treatment on the mean corpuscular hemoglobin concentration (MCHC), density, and water content of the RBCs differed in the two species. The dog RBCs became low in MCHC, high in ion and water content, and low in mean density. Thus, HU can raise MCV and lower MCHC without influencing fetal hemoglobin synthesis. A different pattern was seen in the sickle cell patients during HU treatment. Although the MCV of their RBCs increased, there was no change in MCHC, ion content, or mean density. A notable change in the sickle cell patients' blood was that two subpopulations of cells were nearly eliminated during HU treatment; the hypodense reticulocyte fraction and the hyperdense fraction that contains irreversibly sickled cells. These findings lead us to suggest that trials of HU in sickle cell disease must recognize the possibility that any beneficial effect of this agent might be due not only to an increase in hemoglobin F alone, but perhaps also to the associated increase in MCV or the altered RBC density profile.
Authors:
E P Orringer; D S Blythe; A E Johnson; G Phillips; G J Dover; J C Parker
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  78     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1991 Jul 
Date Detail:
Created Date:  1991-08-19     Completed Date:  1991-08-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  212-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of North Carolina at Chapel Hill 27599-7600.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Anemia, Sickle Cell / blood*,  drug therapy
Animals
Dogs
Erythrocyte Count / drug effects
Erythrocytes / chemistry,  drug effects*,  metabolism
Fetal Hemoglobin / analysis*,  metabolism
Humans
Hydroxyurea / administration & dosage,  pharmacology*,  therapeutic use
Osmolar Concentration
Water / analysis*,  metabolism
Grant Support
ID/Acronym/Agency:
DK-11356/DK/NIDDK NIH HHS; HL-28391/HL/NHLBI NIH HHS; HL-40169/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
127-07-1/Hydroxyurea; 7732-18-5/Water; 9034-63-3/Fetal Hemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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