Document Detail


Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea.
MedLine Citation:
PMID:  1690857     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Because fetal hemoglobin contains gammaglobin chains instead of beta chains, it is not affected by the genetic defect that causes sickle cell disease. Increased levels of fetal hemoglobin decrease the tendency toward intracellular polymerization of sickle hemoglobin that characterizes this disease. Hydroxyurea is one of several cytostatic agents that have been shown to increase the production of fetal hemoglobin in some patients with sickle cell disease. We studied the effects of hydroxyurea administration in 10 hospitalized patients with sickle cell disease, each of whom was treated for three months. Seven patients responded with a 2- to 10-fold increase in fetal hemoglobin, from a mean (+/- SD) of 1.6 +/- 1.6 percent of total hemoglobin to 6.8 +/- 4.7 percent; three patients had fetal-hemoglobin levels of 10 to 15 percent of total hemoglobin. Three did not respond to treatment. Four of the patients who responded were retreated with hydroxyurea after one to four months without treatment and were found to have larger increases in fetal-hemoglobin levels. In most patients, levels were still rising at the end of the study, even after 90 days of therapy. Fetal-hemoglobin levels tended to peak at dosages of hydroxyurea that were myelosuppressive. In the patients who responded to treatment, there were significant increases in the percentage of reticulocytes and erythrocytes containing fetal hemoglobin and in the amount of fetal hemoglobin within these cells. The percentage of dense red cells decreased in the patients who responded to treatment. The tendency toward intracellular polymerization at physiologic oxygen saturation was reduced by about 33 percent in the cells containing fetal hemoglobin, whereas there was no change in the other cells. We conclude that hydroxyurea is effective in increasing the production of fetal hemoglobin, which in this study was found to be associated with a small decrease in hemolysis and an increase in hemoglobin levels despite myelosuppression. Controlled, prospective trials are necessary to establish whether these effects will lead to clinical benefit.
Authors:
G P Rodgers; G J Dover; C T Noguchi; A N Schechter; A W Nienhuis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The New England journal of medicine     Volume:  322     ISSN:  0028-4793     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  1990 Apr 
Date Detail:
Created Date:  1990-04-27     Completed Date:  1990-04-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1037-45     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anemia, Sickle Cell / blood*,  drug therapy
Blood Cell Count
Bone Marrow / drug effects
Female
Fetal Hemoglobin / analysis*
Hematopoiesis / drug effects
Hemoglobin, Sickle / metabolism
Hemoglobins / analysis
Humans
Hydroxyurea / adverse effects,  pharmacology*,  therapeutic use
Male
Polymers
Grant Support
ID/Acronym/Agency:
HL-28028/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobin, Sickle; 0/Hemoglobins; 0/Polymers; 127-07-1/Hydroxyurea; 9034-63-3/Fetal Hemoglobin

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


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