Skip to main content
SpringerLink
Log in
Book cover

L-Arginine in Clinical Nutrition pp 497–512Cite as

l-Arginine Therapy in Sickle Cell Disease

  • Chapter
  • First Online:

  • 1387 Accesses

Part of the book series: Nutrition and Health ((NH))

Abstract

Sickle cell disease (SCD) affects nearly 100,000 people in the USA and millions worldwide. Genetically, SCD is caused by an amino acid substitution of valine for glutamic acid in the sixth position of the β subunits of hemoglobin. This structural change results in the intracellular polymerization of the deoxygenated hemoglobin molecules under hypoxic conditions. Intracellular polymer increases erythrocyte rigidity and ultimately damages and distorts the erythrocyte membrane. This produces a rigid “sickled” red cell with altered rheological and adhesive properties that becomes entrapped in the microcirculation and gives rise to the vaso-occlusive events characteristic of the disease. The clinical phenotype of SCD varies widely and is characterized by anemia, severe pain, and potentially life-threatening complications such as bacterial sepsis, splenic sequestration, acute chest syndrome (ACS), stroke, and chronic organ damage. These and other manifestations result from acute and chronic hemolysis and intermittent episodes of vascular occlusion that cause tissue injury and organ dysfunction (Stuart and Nagel. Lancet 364(9442):1343–1360, 2004; Gladwin and Vichinsky. N Engl J Med 359(21):2254–2265, 2008).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ACS:

Acute chest syndrome

ADMA:

Asymmetric dimethylarginine

CAT:

Cationic amino acid transporter

CSCC:

Comprehensive sickle cell centers

ED:

Emergency department

GAB:

Global l-arginine bioavailability

HU:

Hydroxyurea

K m :

Michaelis affinity constant

LDH:

Lactate dehydrogenase

MACE:

Major adverse cardiovascular events

NADP:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

NOHA:

N-hydroxy-l-arginine

NOS:

Nitric oxide synthase

NO x :

NO metabolites

PICU:

Pediatric intensive care unit

VOE:

Vaso-occlusive painful episodes

References

  1. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364(9442):1343–60.

    Article  PubMed  Google Scholar 

  2. Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med. 2008;359(21):2254–65.

    Article  CAS  PubMed  Google Scholar 

  3. Hebbel RP, Osarogiagbon KD. The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation. 2004;11:129–51.

    Article  CAS  PubMed  Google Scholar 

  4. Frenette PS. Sickle cell vaso-occlusion: multistep and multicellular paradigm. Curr Opin Hematol. 2002;9(2):101–6.

    Article  PubMed  Google Scholar 

  5. Parise LV, Telen MJ. Erythrocyte adhesion in sickle cell disease. Curr Hematol Rep. 2003;2(2):102–8.

    PubMed  Google Scholar 

  6. Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated l-arginine metabolism, hemolysis-associated pulmonary hypertension and mortality in sickle cell disease. JAMA. 2005;294(1):81–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morris Jr SM. Arginases and l-arginine deficiency syndromes. Curr Opin Clin Nutr Metab Care. 2012;15(1):64–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Morris CR. Alterations of the l-arginine metabolome in sickle cell disease: a growing rationale for l-arginine therapy. Hematol Oncol Clin North Am. 2014;28(2):301–21.

    Article  PubMed  Google Scholar 

  9. Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program. 2008;2008:177–85.

    Google Scholar 

  10. Cox SE, Makani J, Komba AN, et al. Global l-arginine bioavailability in Tanzanian sickle cell anaemia patients at steady-state: a nested case control study of deaths versus survivors. Br J Haematol. 2011;155(4):522–4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Stuehr DJ, Kwon N, Nathan CF, Griffith OW, Felman PL, Wiseman J. N-Hydroxyl-l-arginine is an intermediate in the biosynthesis of nitric oxide for l-arginine. J Biol Chem. 1991;266:6259–63.

    CAS  PubMed  Google Scholar 

  12. Stuehr DJ, Kwon NS, Nathan CF. FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem Biophys Res Commun. 1990;168(2):558–65.

    Article  CAS  PubMed  Google Scholar 

  13. Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. Oral l-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll Cardiol. 1995;26:1054–61.

    Article  CAS  PubMed  Google Scholar 

  14. Moncada S, Higgs A. The l-arginine-nitric oxide pathway. N Engl J Med. 1993;329:2002–12.

    Article  CAS  PubMed  Google Scholar 

  15. Kaul DK, Hebbel RP. Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J Clin Invest. 2000;106:411–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Peng H-B, Spiecker M, Liao J. Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation. J Immunol. 1998;161:1970–6.

    CAS  PubMed  Google Scholar 

  17. Reiter CD, Gladwin MT. An emerging role for nitric oxide in sickle cell disease vascular homeostatis and therapy. Curr Opin Hematol. 2003;10:99–107.

    Article  CAS  PubMed  Google Scholar 

  18. Reiter C, Wang X, Tanus-Santos J, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle cell disease. Nat Med. 2002;8:1383–9.

    Article  CAS  PubMed  Google Scholar 

  19. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293:1653–62.

    Article  CAS  PubMed  Google Scholar 

  20. Aslan M, Ryan TM, Adler B, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci U S A. 2001;98(26):15215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaul DK, Liu XD, Fabry ME, Nagel RL. Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol. 2000;278:H1799–806.

    CAS  PubMed  Google Scholar 

  22. Eberhardt RT, McMahon L, Duffy SJ, et al. Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol. 2003;74:104–11.

    Article  CAS  PubMed  Google Scholar 

  23. Gladwin M, Schechter A, Ognibene F, et al. Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation. 2003;107:271–8.

    Article  CAS  PubMed  Google Scholar 

  24. Belhassen L, Pelle G, Sediame S, et al. Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation. Blood. 2001;97:1584–9.

    Article  CAS  PubMed  Google Scholar 

  25. Rees DC, Cervi P, Grimwade D, et al. The metabolites of nitric oxide in sickle-cell disease. Br J Haematol. 1995;91:834–7.

    Article  CAS  PubMed  Google Scholar 

  26. Pegelow CH, Colangelo L, Steinberg M, et al. Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia. Am J Med. 1997;102(2):171–7.

    Article  CAS  PubMed  Google Scholar 

  27. Morris CR, Kuypers FA, Larkin S, Vichinsky E, Styles L. Patterns of l-arginine and nitric oxide in sickle cell disease patients with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol. 2000;22:515–20.

    Article  CAS  PubMed  Google Scholar 

  28. Lopez BL, Barnett J, Ballas SK, Christopher TA, Davis-Moon L, Ma X. Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis. Acad Emerg Med. 1996;3:1098–103.

    Article  CAS  PubMed  Google Scholar 

  29. Lopez B, Davis-Moon L, Ballas S. Sequential nitric oxide measurements during the emergency department treatment of acute vasoocclusive sickle cell crisis. Am J Hematol. 2000;64:15–9.

    Article  CAS  PubMed  Google Scholar 

  30. Enwonwu CO. Increased metabolic demand for l-arginine in sickle cell anaemia. Med Sci Res. 1989;17:997–8.

    CAS  Google Scholar 

  31. Waugh W, Daeschner C, Files B, Gordon D. Evidence that l-arginine is a key amino acid in sickle cell anemia—a preliminary report. Nutr Res. 1999;19:501–18.

    Article  CAS  Google Scholar 

  32. Morris CR, Kuypers FA, Larkin S, et al. l-Arginine therapy: a novel strategy to increase nitric oxide production in sickle cell disease. Br J Haematol. 2000;111:498–500.

    Article  CAS  PubMed  Google Scholar 

  33. Lopez B, Kreshak A, Morris CR, Davis-Moon L, Ballas S, Ma X. l-arginine levels are diminished in adult acute vaso-occlusive sickle cell crisis in the emergency department. Br J Haematol. 2003;120:532–4.

    Article  CAS  PubMed  Google Scholar 

  34. Takemoto K, Ogino K, Shibamori M, et al. Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma. Am J Physiol Lung Cell Mol Physiol. 2007;293(6):L1419–26.

    Article  CAS  PubMed  Google Scholar 

  35. Wu G, Morris SM. l-Arginine metabolism: nitric oxide and beyond. Biochem J. 1998;336:1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006;107(6):2279–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Morris CR. Asthma management: reinventing the wheel in sickle cell disease. Am J Hematol. 2009;84(4):234–41.

    Article  PubMed  Google Scholar 

  38. Morris CR, Poljakovic M, Lavisha L, Machado L, Kuypers F, Morris Jr SM. Decreased l-arginine bioavailability and increased arginase activity in asthma. Am J Respir Crit Care Med. 2004;170:148–53.

    Article  PubMed  Google Scholar 

  39. Morris CR, Morris Jr SM, Hagar W, et al. l-Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003;168:63–9.

    Article  PubMed  Google Scholar 

  40. Tang WH, Wang Z, Cho L, Brennan DM, Hazen SL. Diminished global l-arginine bioavailability and increased l-arginine catabolism as metabolic profile of increased cardiovascular risk. J Am Coll Cardiol. 2009;53(22):2061–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kato GJ, Wang Z, Machado RF, Blackwelder WC, Taylor 6th JG, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. 2009;145(4):506–13.

    Article  CAS  PubMed  Google Scholar 

  42. Berka V, Wu G, Yeh HC, Palmer G, Tsai AL. Three different oxygen-induced radical species in endothelial nitric-oxide synthase oxygenase domain under regulation by l-arginine and tetrahydrobiopterin. J Biol Chem. 2004;279(31):32243–51.

    Article  CAS  PubMed  Google Scholar 

  43. Xia Y, Dawson V, Dawson T, Snyder S, Zweier J. Nitric oxide synthase generates superoxide and nitric oxide in l-arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc Natl Acad Sci USA. 1996;93:6770–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wood KC, Hebbel RP, Lefer DJ, Granger DN. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med. 2006;40(8):1443–53.

    Article  CAS  PubMed  Google Scholar 

  45. Morris CR, Suh JH, Hagar W, et al. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. Blood. 2008;140:104–12.

    Google Scholar 

  46. Bank N, Aynedjian H, Qiu J, et al. Renal nitric oxide synthases in transgenic sickle cell mice. Kidney Int. 1996;50:184–9.

    Article  CAS  PubMed  Google Scholar 

  47. Hsu LL, Champion HC, Campbell-Lee SA, et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood. 2007;109:3088–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Barnett CF, Hsue PY, Machado RF. Pulmonary hypertension: an increasingly recognized complication of hereditary hemolytic anemias and HIV infection. JAMA. 2008;299(3):324–31.

    Article  CAS  PubMed  Google Scholar 

  49. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007;21(1):37–47.

    Article  PubMed  Google Scholar 

  50. Morris C, Kuypers F, Kato G, et al. Hemolysis-associated pulmonary hypertension in thalassemia. Ann N Y Acad Sci. 2005;1054:481–5.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Potoka KP, Gladwin MT. Vasculopathy and pulmonary hypertension in sickle cell disease. Am J Physiol Lung Cell Mol Physiol. 2015;308(4):L314–24. doi:10.1152/ajplung.00252.2014.

    Article  CAS  PubMed  Google Scholar 

  52. Gladwin MT, Ofori-Acquah SF. Erythroid DAMPs drive inflammation in SCD. Blood. 2014;123(24):3689–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Aslan M, Freeman BA. Oxidant-mediated impairment of nitric oxide signaling in sickle cell disease—mechanisms and consequences. Cell Mol Biol (Noisy-le-Grand). 2004;50(1):95–105.

    CAS  Google Scholar 

  54. Donadee C, Raat NJ, Kanias T, et al. Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation. 2011;124(4):465–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia. Ann N Y Acad Sci. 2010;1202:205–13.

    Article  CAS  PubMed  Google Scholar 

  56. Omodeo-Sale F, Cortelezzi L, Vommaro Z, Scaccabarozzi D, Dondorp AM. Dysregulation of l-arginine metabolism and bioavailability associated to free plasma heme. Am J Physiol Cell Physiol. 2010;299(1):C148–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Morris CR, Kim H, Klings ES, et al. Dysregulated l-arginine metabolism and cardiopulmonary dysfunction in patients with thalassaemia. Br J Haematol. 2015;169(6):887–98 [Epub ahead of print].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Morris CR, Kim HY, Wood J, et al. Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension. Haematologica. 2013;98(9):1359–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Saraf SL, Zhang X, Kanias T, et al. Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia. Br J Haematol. 2014;164(5):729–39.

    Article  CAS  PubMed  Google Scholar 

  60. Gornik HL, Creager MA. l-Arginine and endothelial and vascular health. J Nutr. 2004;134(10 Suppl):2880S–7. Discussion 2895S.

    CAS  PubMed  Google Scholar 

  61. Romero J, Suzuka S, Nagel R, Fabry M. l-Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood. 2002;99:1103–8.

    Article  CAS  PubMed  Google Scholar 

  62. Manci EA, Hyacinth HI, Capers PL, et al. High protein diet attenuates histopathologic organ damage and vascular leakage in transgenic murine model of sickle cell anemia. Exp Biol Med (Maywood). 2014;239(8):966–74.

    Article  Google Scholar 

  63. Dasgupta T, Hebbel RP, Kaul DK. Protective effect of l-arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med. 2006;41(12):1771–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kaul DK, Zhang X, Dasgupta T, Fabry ME. l-Arginine therapy of transgenic-knockout sickle mice improves microvascular function by reducing non-nitric oxide vasodilators, hemolysis, and oxidative stress. Am J Physiol Heart Circ Physiol. 2008;295(1):H39–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Little JA, Hauser KP, Martyr SE, et al. Hematologic, biochemical, and cardiopulmonary effects of l-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy. Eur J Haematol. 2009;82(4):315–21.

    Article  CAS  PubMed  Google Scholar 

  66. Gladwin MT, Barst RJ, Castro OL, et al. Pulmonary hypertension and NO in sickle cell. Blood. 2010;116(5):852–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bunn HF, Nathan DG, Dover GJ, et al. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010;116(5):687–92.

    Article  CAS  PubMed  Google Scholar 

  68. Morris CR, Teehankee C, Kato G, et al. Decreased l-arginine bioavailability contributes to the pathogenesis of pulmonary artery hypertension. In: American College of Cardiology Annual Meeting, Orlando, FL, 6–9 Mar 2005.

    Google Scholar 

  69. Morris CR. New strategies for the treatment of pulmonary hypertension in sickle cell disease: the rationale for l-arginine therapy. Treat Respir Med. 2006;5(1):31–45.

    Article  CAS  PubMed  Google Scholar 

  70. Morris CR, Gladwin MT, Kato G. Nitric oxide and l-arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med. 2008;8:81–90.

    Article  Google Scholar 

  71. Sher GD, Olivieri NG. Rapid healing of leg ulcers during l-arginine butyrate therapy in patients with sickle cell disease and thalassemia. Blood. 1994;84:2378–80.

    CAS  PubMed  Google Scholar 

  72. McMahon L, Tamary H, Askin M, et al. A randomized phase II trial of l-Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers. Br J Haematol. 2010;151(5):516–24.

    Article  CAS  PubMed  Google Scholar 

  73. Morris CR, Vichinsky EP, van Warmerdam J, et al. Hydroxyurea and l-arginine therapy: impact on nitric oxide production in sickle cell disease. J Pediatr Hematol Oncol. 2003;25:629–34.

    Article  PubMed  Google Scholar 

  74. Morris CR. Reduced global l-arginine bioavailability: a common mechanism of vasculopathy in sickle cell disease and pulmonary hypertension. Blood. 2010. http://bloodjournal.hematologylibrary.org/cgi/eletters/blood-2010-02-268193v1 [e-letter] 22 Apr 2010.

  75. Maxwell AJ, Cooke JP. Cardiovascular effects of l-arginine. Curr Opin Nephrol Hypertens. 1998;7:63–70.

    Article  CAS  PubMed  Google Scholar 

  76. Merimee TJ, Rabinowitz D, Riggs L, Burgess JA, Rimoin DL, McKusick VA. Plasma growth hormone after l-arginine infusion. N Engl J Med. 1967;276:434–9.

    Article  CAS  PubMed  Google Scholar 

  77. Yeo TW, Rooslamiati I, Gitawati R, et al. Pharmacokinetics of l-arginine in adults with moderately severe malaria. Antimicrob Agents Chemother. 2008;52(12):4381–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Yeo TW, Lampah DA, Rooslamiati I, et al. A randomized pilot study of l-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics. PLoS One. 2013;8(7):e69587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yeo TW, Lampah DA, Gitawati R, et al. Safety profile of l-arginine infusion in moderately severe falciparum malaria. PLoS One. 2008;3(6):e2347.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Elias DB, Barbosa MC, Rocha LB, et al. l-arginine as an adjuvant drug in the treatment of sickle cell anaemia. Br J Haematol. 2013;160(3):410–2.

    Article  CAS  PubMed  Google Scholar 

  81. Brousseau DC, Owens PL, Mosso AL, Panepinto JA, Steiner CA. Acute care utilization and rehospitalizations for sickle cell disease. JAMA. 2010;303(13):1288–94.

    Article  CAS  PubMed  Google Scholar 

  82. Alexander GM, Reichenberger E, Peterlin BL, Perreault MJ, Grothusen JR, Schwartzman RJ. Plasma amino acids changes in complex regional pain syndrome. Pain Res Treat. 2013;2013:742407.

    PubMed  PubMed Central  Google Scholar 

  83. Morris CR, Kuypers FA, Lavrisha L, et al. A randomized, placebo-controlled trial of l-arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica. 2013;98(9):1375–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gladwin MT, Kato GJ, Weiner D, et al. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011;305(9):893–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Machado RF, Barst RJ, Yovetich NA, et al. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011;118(4):855–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Little JA, McGowan VR, Kato GJ, et al. Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institutes of Health and a literature review. Haematologica. 2006;91(8):1076–83.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory-Children’s Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, 1760 Haygood Drive NE, W458, Atlanta, GA, 30322, USA

    Claudia R. Morris MD, FAAP

Authors
  1. Claudia R. Morris MD, FAAP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia R. Morris MD, FAAP .

Editor information

Editors and Affiliations

  1. Faculty of Science & Technology Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department Nutrition and Dietetics Nutritional Sciences Division School of Biomedical & Health Sciences, King’s College London, London, United Kingdom

    Victor R. Preedy

  3. Nutritional Sciences Research Division Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Rajkumar Rajendram

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Morris, C.R. (2017). l-Arginine Therapy in Sickle Cell Disease. In: Patel, V., Preedy, V., Rajendram, R. (eds) L-Arginine in Clinical Nutrition. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-26009-9_39

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26009-9_39

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-26007-5

  • Online ISBN: 978-3-319-26009-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation