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April 24, 1991, Vol 265, No. 16 >
ARTICLE | April 24, 1991

Recent Approaches to the Treatment of Sickle Cell Anemia FREE

Griffin P. Rodgers, MD
[+] Author Affiliations

Reprint requests to Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg 10, Room 9N-318, National Institutes of Health, Bethesda, MD 20892 (Dr Rodgers).


JAMA. 1991;265(16):2097-2101. doi:10.1001/jama.1991.03460160075033
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References

SELECTED CASE  A 35-YEAR-OLD man whose sickle cell anemia was first diagnosed at the age of 3 years was referred to the Clinical Center at the National Institutes of Health (NIH), Bethesda, Md, for evaluation and management of his disease. He had a history of frequent vaso-occlusive crises, skin ulcers, and recurrent bacterial pneumonias. He suffered a left hemispheric cerebrovascular accident at the age of 12 years and since then has had a residual seizure disorder. He regularly received transfusions every 3 months from ages 14 to 35 years and at the time of admission to the NIH had an estimated transfusion burden well in excess of 250 U. Other complications of his disease included proliferative sickle retinopathy and cardiomyopathy, which had led to worsening tolerance for exercise. His major complaint, however, was chronic pain in his knees, shins, back, elbows, and shoulders for which he required 4 mg of

REFERENCES

1 +
Ham TH, Castle WB.  Relation of increased hypotonic fragility and of erythrostasis to the mechanism of hemolysis in certain anemias . Trans Assoc Am Physicians. 1940;;55:127-132.
2 +
Conley CL.  Sickle cell anemia—the first molecular disease . In: Wintrobe M, ed. Blood, Pure and Eloquent . New York, NY: McGraw-Hill International Book Co; 1980;:319-371.
3 +
Eaton WA, Hofrichter J, Ross PD.  Delay time of gelation: a possible determinant of clinical severity in sickle-cell disease . Blood. 1976;;47:621-630.
4 +
Schechter AN, Noguchi CT, Rodgers GP.  Sickle cell anemia . In: Stamatoyannopoulos G, Nienhuis AW, Leder P, Majerus PW, eds. The Molecular Basis of Blood Diseases . Philadelphia, Pa: WB Saunders Co; 1987;:179-218.
5 +
Brittenham GM, Schechter AN, Noguchi CT.  Hemoglobin S polymerization: primary determinant of the hemolytic and clinical severity of the sickling syndromes . Blood. 1985;;65:183-189.
6 +
Embury S.  The clinical pathophysiology of sickle-cell disease . Ann Rev Med. 1986;;37:361-372.
7 +
Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects . Philadelphia, Pa: WB Saunders Co; 1986;.
8 +
Lubin B, Vichinsky E.  Sickle-cell disease . In: Benz EJ, Cohen HJ, Furie B, Hoffman R, Shattil S, eds. Hematology: Basic Principles and Practice . New York, NY: Churchill Livingstone Inc; 1990;:450-471.
9 +
Charache S, Dover GJ, Smith K, et al.  Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA . Proc Natl Acad Sci U S A. 1983;;80:4842-4846.
10 +
Ley TJ, DeSimone J, Noguchi CT, et al.  5-Azacytidine increases γ-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia . Blood. 1983;;62:370-380.
11 +
Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG.  Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia . J Clin Invest. 1984;;74:652-656.
12 +
Veith R, Galanello R, Papayannopoulou T, Stamatoyannopoulos G.  Stimulation of F cell production in patients with sickle cell anemia treated with cytarabine or hydroxyurea . N Engl J Med. 1985;;313:1571-1575.
13 +
Dover GJ, Humphries RK, Moore JG, et al.  Hydroxyurea induction of fetal hemoglobin production in sickle-cell disease: relationship between cytotoxicity and F cell production . Blood. 1986;;67: 735-738.
14 +
Charache S, Dover GJ, Moyer MA, Moore JW.  Hydroxyurea-inducted augmentation of fetal hemoglobin production in patients with sickle cell anemia . Blood. 1988;;69:109-116.
15 +
Rodgers GP, Roy MS, Noguchi CT, Schechter AN.  Is there a role for selective vasodilatation in the management of sickle-cell disease? Blood. 1988;;71:597-602.
16 +
Noguchi CT, Rodgers GP, Serjeant G, Schechter AN.  Levels of fetal hemoglobin necessary for treatment of sickle-cell disease . N Engl J Med. 1988;;318:96-99.
17 +
Rodgers GP, Dover GJ, Noguchi CT, Schechter AN, Nienhuis AW.  Hematological responses in patients with sickle-cell disease to treatment with hydroxyurea . N Engl J Med. 1990;;322; 1037-1045.
18 +
Letvin NI, Linch DC, Beardsley GP, et al.  Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea . N Engl J Med. 1984;;310:869-873.
19 +
Papayannopoulou TH, Torrealba-de Ron A, Veith R, et al.  Arabinosylcytosine induces fetal hemoglobin in baboons by perturbing cell differentiation kinetics . Science. 1984;;224:617-618.
20 +
Torrealba-de Ron AT, Papayannopoulou T, Knapp MS, et al.  Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine . Blood. 1984;;63:201-210.
21 +
Galanello R, Stamatoyannopoulos G, Papayannopoulou T.  Mechanism of HbF stimulation by S-stage compounds: in vitro studies with bone marrow cells exposed to 5-azacytidine, Ara-C, or hydroxyurea . J Clin Invest. 1988;;81:1209-1216.
22 +
Alter BP, Gilbert HS.  The effect of hydroxyurea on hemoglobin F in patients with myeloproliferative syndromes . Blood. 1985;;66:373-379.
23 +
Al-Khatti A, Veith RW, Papayannopoulou T, et al.  Stimulation of fetal hemoglobin synthesis by erythropoietin in baboons . N Engl J Med. 1987;;317:415-420.
24 +
McDonagh KT, Dover GJ, Donahue R, et al.  Manipulation of the HbF production with hematopoietic growth factors . In: Stamatoyannopoulos G, Nienhuis AW, eds. Hemoglobin Switching, Part B: Cellular and Molecular Mechanisms . New York, NY: Alan R Liss Inc; 1989;:295-306.
25 +
Goldberg MA, Brugnara C, Dover GJ, Schapira L, Charache S, Bunn HF.  Treatment of sickle cell anemia with hydroxyurea and erythropoietin . N Engl J Med. 1990;;323:366-372.
26 +
Nienhuis AW, Wolfe LC.  The thalassemias . In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood . Philadelphia, Pa: WB Saunders Co; 1987;:699-778.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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1 +
Ham TH, Castle WB.  Relation of increased hypotonic fragility and of erythrostasis to the mechanism of hemolysis in certain anemias . Trans Assoc Am Physicians. 1940;;55:127-132.
2 +
Conley CL.  Sickle cell anemia—the first molecular disease . In: Wintrobe M, ed. Blood, Pure and Eloquent . New York, NY: McGraw-Hill International Book Co; 1980;:319-371.
3 +
Eaton WA, Hofrichter J, Ross PD.  Delay time of gelation: a possible determinant of clinical severity in sickle-cell disease . Blood. 1976;;47:621-630.
4 +
Schechter AN, Noguchi CT, Rodgers GP.  Sickle cell anemia . In: Stamatoyannopoulos G, Nienhuis AW, Leder P, Majerus PW, eds. The Molecular Basis of Blood Diseases . Philadelphia, Pa: WB Saunders Co; 1987;:179-218.
5 +
Brittenham GM, Schechter AN, Noguchi CT.  Hemoglobin S polymerization: primary determinant of the hemolytic and clinical severity of the sickling syndromes . Blood. 1985;;65:183-189.
6 +
Embury S.  The clinical pathophysiology of sickle-cell disease . Ann Rev Med. 1986;;37:361-372.
7 +
Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects . Philadelphia, Pa: WB Saunders Co; 1986;.
8 +
Lubin B, Vichinsky E.  Sickle-cell disease . In: Benz EJ, Cohen HJ, Furie B, Hoffman R, Shattil S, eds. Hematology: Basic Principles and Practice . New York, NY: Churchill Livingstone Inc; 1990;:450-471.
9 +
Charache S, Dover GJ, Smith K, et al.  Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA . Proc Natl Acad Sci U S A. 1983;;80:4842-4846.
10 +
Ley TJ, DeSimone J, Noguchi CT, et al.  5-Azacytidine increases γ-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia . Blood. 1983;;62:370-380.
11 +
Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG.  Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia . J Clin Invest. 1984;;74:652-656.
12 +
Veith R, Galanello R, Papayannopoulou T, Stamatoyannopoulos G.  Stimulation of F cell production in patients with sickle cell anemia treated with cytarabine or hydroxyurea . N Engl J Med. 1985;;313:1571-1575.
13 +
Dover GJ, Humphries RK, Moore JG, et al.  Hydroxyurea induction of fetal hemoglobin production in sickle-cell disease: relationship between cytotoxicity and F cell production . Blood. 1986;;67: 735-738.
14 +
Charache S, Dover GJ, Moyer MA, Moore JW.  Hydroxyurea-inducted augmentation of fetal hemoglobin production in patients with sickle cell anemia . Blood. 1988;;69:109-116.
15 +
Rodgers GP, Roy MS, Noguchi CT, Schechter AN.  Is there a role for selective vasodilatation in the management of sickle-cell disease? Blood. 1988;;71:597-602.
16 +
Noguchi CT, Rodgers GP, Serjeant G, Schechter AN.  Levels of fetal hemoglobin necessary for treatment of sickle-cell disease . N Engl J Med. 1988;;318:96-99.
17 +
Rodgers GP, Dover GJ, Noguchi CT, Schechter AN, Nienhuis AW.  Hematological responses in patients with sickle-cell disease to treatment with hydroxyurea . N Engl J Med. 1990;;322; 1037-1045.
18 +
Letvin NI, Linch DC, Beardsley GP, et al.  Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea . N Engl J Med. 1984;;310:869-873.
19 +
Papayannopoulou TH, Torrealba-de Ron A, Veith R, et al.  Arabinosylcytosine induces fetal hemoglobin in baboons by perturbing cell differentiation kinetics . Science. 1984;;224:617-618.
20 +
Torrealba-de Ron AT, Papayannopoulou T, Knapp MS, et al.  Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine . Blood. 1984;;63:201-210.
21 +
Galanello R, Stamatoyannopoulos G, Papayannopoulou T.  Mechanism of HbF stimulation by S-stage compounds: in vitro studies with bone marrow cells exposed to 5-azacytidine, Ara-C, or hydroxyurea . J Clin Invest. 1988;;81:1209-1216.
22 +
Alter BP, Gilbert HS.  The effect of hydroxyurea on hemoglobin F in patients with myeloproliferative syndromes . Blood. 1985;;66:373-379.
23 +
Al-Khatti A, Veith RW, Papayannopoulou T, et al.  Stimulation of fetal hemoglobin synthesis by erythropoietin in baboons . N Engl J Med. 1987;;317:415-420.
24 +
McDonagh KT, Dover GJ, Donahue R, et al.  Manipulation of the HbF production with hematopoietic growth factors . In: Stamatoyannopoulos G, Nienhuis AW, eds. Hemoglobin Switching, Part B: Cellular and Molecular Mechanisms . New York, NY: Alan R Liss Inc; 1989;:295-306.
25 +
Goldberg MA, Brugnara C, Dover GJ, Schapira L, Charache S, Bunn HF.  Treatment of sickle cell anemia with hydroxyurea and erythropoietin . N Engl J Med. 1990;;323:366-372.
26 +
Nienhuis AW, Wolfe LC.  The thalassemias . In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood . Philadelphia, Pa: WB Saunders Co; 1987;:699-778.

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