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Treatment of sickle cell anemia with hydroxyurea and erythropoietin.

Abstract

BACKGROUND

Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production.

METHODS AND RESULTS

We treated five patients with sickle cell disease with escalating doses of intravenous erythropoietin for eight weeks. Three of these patients were subsequently treated with daily doses of oral hydroxyurea. After the optimal dose was determined, erythropoietin was then given along with hydroxyurea for four weeks. Treatment with erythropoietin, either alone or in combination with hydroxyurea, had no significant effect on the percentage of hemoglobin F-containing reticulocytes (F reticulocytes) or red cells (F cells). In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F. In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival. Hydroxyurea treatment also resulted in a decrease in the percentage of irreversibly sickled cells and sickling at partial oxygen saturation, an increase in oxygen affinity and total red-cell cation content, and a reduction in potassium-chloride cotransport. All three patients had a decrease in the number of pain crises.

CONCLUSIONS

This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Brigham and Women's Hospital, MA 02115.

    , , , ,

    Source

    The New England journal of medicine 323:6 1990 Aug 09 pg 366-72

    MeSH

    Administration, Oral
    Anemia, Sickle Cell
    Drug Administration Schedule
    Drug Evaluation
    Drug Therapy, Combination
    Erythrocytes
    Erythropoietin
    Fetal Hemoglobin
    Hemoglobin, Sickle
    Hemolysis
    Humans
    Hydroxyurea
    Recombinant Proteins
    Reticulocytes

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    1695325

    Citation

    Goldberg, M A., et al. "Treatment of Sickle Cell Anemia With Hydroxyurea and Erythropoietin." The New England Journal of Medicine, vol. 323, no. 6, 1990, pp. 366-72.
    Goldberg MA, Brugnara C, Dover GJ, et al. Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N Engl J Med. 1990;323(6):366-72.
    Goldberg, M. A., Brugnara, C., Dover, G. J., Schapira, L., Charache, S., & Bunn, H. F. (1990). Treatment of sickle cell anemia with hydroxyurea and erythropoietin. The New England Journal of Medicine, 323(6), pp. 366-72.
    Goldberg MA, et al. Treatment of Sickle Cell Anemia With Hydroxyurea and Erythropoietin. N Engl J Med. 1990 Aug 9;323(6):366-72. PubMed PMID: 1695325.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Treatment of sickle cell anemia with hydroxyurea and erythropoietin. AU - Goldberg,M A, AU - Brugnara,C, AU - Dover,G J, AU - Schapira,L, AU - Charache,S, AU - Bunn,H F, PY - 1990/8/9/pubmed PY - 1990/8/9/medline PY - 1990/8/9/entrez SP - 366 EP - 72 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 323 IS - 6 N2 - BACKGROUND: Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production. METHODS AND RESULTS: We treated five patients with sickle cell disease with escalating doses of intravenous erythropoietin for eight weeks. Three of these patients were subsequently treated with daily doses of oral hydroxyurea. After the optimal dose was determined, erythropoietin was then given along with hydroxyurea for four weeks. Treatment with erythropoietin, either alone or in combination with hydroxyurea, had no significant effect on the percentage of hemoglobin F-containing reticulocytes (F reticulocytes) or red cells (F cells). In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F. In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival. Hydroxyurea treatment also resulted in a decrease in the percentage of irreversibly sickled cells and sickling at partial oxygen saturation, an increase in oxygen affinity and total red-cell cation content, and a reduction in potassium-chloride cotransport. All three patients had a decrease in the number of pain crises. CONCLUSIONS: This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1695325/Treatment_of_sickle_cell_anemia_with_hydroxyurea_and_erythropoietin_ L2 - https://www.nejm.org/doi/10.1056/NEJM199008093230602?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -