If a person has two normal copies of the hemoglobin allele, which statements are true?

  • Adamkiewicz TV, Sarnaik S, Buchanan GR, Iyer RV, Miller ST, Pegelow CH, Rogers ZR, Vichinsky E, Elliott J, Facklam RR, O'Brien KL, Schwartz B, Van Beneden CA, Cannon MJ, Eckman JR, Keyserling H, Sullivan K, Wong WY, Wang WC. Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination. J Pediatr. 2003;143:438–44. [PubMed: 14571216]

  • Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005;353:2769–78. [PubMed: 16382063]

  • Adams RJ, Brambilla DJ, Granger S, Gallagher D, Vichinsky E, Abboud MR, Pegelow CH, Woods G, Rohde EM, Nichols FT, Jones A, Luden JP, Bowman L, Hagner S, Morales KH, Roach ES, et al. Stroke and conversion to high risk in children screened with transcranial Doppler ultrasound during the STOP study. Blood. 2004;103:3689–94. [PubMed: 14751925]

  • Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, Abboud M, Gallagher D, Kutlar A, Nichols FT, Bonds DR, Brambilla D. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5–11. [PubMed: 9647873]

  • Adeyoju AB, Olujohungbe AB, Morris J, Yardumian A, Bareford D, Akenova A, Akinyanju O, Cinkotai K, O'Reilly PH. Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study. BJU Int. 2002;90:898–902. [PubMed: 12460353]

  • Alayed N, Kezouh A, Oddy L, Abenhaim HA. Sickle cell disease and pregnancy outcomes: population-based study on 8.8 million births. J Perinat Med. 2014;42:487–92. [PubMed: 24344096]

  • Alfraih F, Aljurf M, Fitzhugh CD, Kassim AA. Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies. Semin Hematol. 2016;53:120–8. [PubMed: 27000737]

  • Aliyu ZY, Kato GJ, Taylor J 6th, Babadoko A, Mamman AI, Gordeuk VR, Gladwin MT. Sickle cell disease and pulmonary hypertension in Africa: a global perspective and review of epidemiology, pathophysiology, and management. Am J Hematol. 2008;83:63–70. [PubMed: 17910044]

  • Aloe A, Krishnamurti L, Kladny B. Testing of collegiate athletes for sickle cell trait: what we, as genetic counselors should know. J Genet Couns. 2011;20:337–40. [PubMed: 21503822]

  • Arkuszewski M, Krejza J, Chen R, Ichord R, Kwiatkowski JL, Bilello M, Zimmerman R, Ohene-Frempong K, Melhem ER. Sickle cell anemia: intracranial stenosis and silent cerebral infarcts in children with low risk of stroke. Adv Med Sci. 2014;59:108–13. [PubMed: 24797985]

  • Arnold SD, Bhatia M, Horan J, Krishnamurti L. Haematopoietic stem cell transplantation for sickle cell disease: current practice and new approaches. Br J Haematol. 2016;174:515–25. [PubMed: 27255787]

  • Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376:429–39. [PMC free article: PMC5481200] [PubMed: 27959701]

  • Austin H, Key NS, Benson JM, Lally C, Dowling NF, Whitsett C, Hooper WC. Sickle cell trait and the risk of venous thromboembolism among blacks. Blood. 2007;110:908–12. [PubMed: 17409269]

  • Bakanay SM, Dainer E, Clair B, Adekile A, Daitch L, Wells L, Holley L, Smith D, Kutlar A. Mortality in sickle cell patients on hydroxyurea therapy. Blood. 2005;105:545–7. [PubMed: 15454485]

  • Baskin MN, Goh XL, Heeney MM, Harper MB. Bacteremia risk and outpatient management of febrile patients with sickle cell disease. Pediatrics. 2013;131:1035–41. [PubMed: 23669523]

  • Bender MA, Seibel G. Sickle cell disease critical elements of care. The Center for Children with Special Needs. Seattle Children's Hospital, Seattle, WA. Available online. 2012. Accessed 4-19-22.

  • Bernaudin F, Verlhac S, Arnaud C, Kamdem A, Chevret S, Hau I, Coïc L, Leveillé E, Lemarchand E, Lesprit E, Abadie I, Medejel N, Madhi F, Lemerle S, Biscardi S, Bardakdjian J, Galactéros F, Torres M, Kuentz M, Ferry C, Socié G, Reinert P, Delacourt C. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood. 2011;117:1130–40. [PubMed: 21068435]

  • Bonham VL, Dover GJ, Brody LC. Screening student athletes for sickle cell trait--a social and clinical experiment. N Engl J Med. 2010;363:997–9. [PubMed: 20825310]

  • Brawley OW, Cornelius LJ, Edwards LR, Gamble VN, Green BL, Inturrisi C, James AH, Laraque D, Mendez M, Montoya CJ, Pollock BH, Robinson L, Scholnik AP, Schori M. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008;148:932–8. [PubMed: 18458271]

  • Cavazza A, Moiani A, Mavilio F. Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther. 2013;24:119–31. [PubMed: 23330935]

  • Chulamokha L, Scholand SJ, Riggio JM, Ballas SK, Horn D, DeSimone JA. Bloodstream infections in hospitalized adults with sickle cell disease: a retrospective analysis. Am J Hematol. 2006;81:723–8. [PubMed: 16795063]

  • Costa VM, Viana MB, Aguiar RA. Pregnancy in patients with sickle cell disease: maternal and perinatal outcomes. J Matern Fetal Neonatal Med. 2015;28:685–9. [PubMed: 24866352]

  • Cui S, Lim KC, Shi L, Lee M, Jearawiriyapaisarn N, Myers G, Campbell A, Harro D, Iwase S, Trievel RC, Rivers A, DeSimone J, Lavelle D, Saunthararajah Y, Engel JD. The LSD1 inhibitor RN-1 induces fetal hemoglobin synthesis and reduces disease pathology in sickle cell mice. Blood. 2015;126:386–96. [PMC free article: PMC4504950] [PubMed: 26031919]

  • Darbari DS, Onyekwere O, Nouraie M, Minniti CP, Luchtman-Jones L, Rana S, Sable C, Ensing G, Dham N, Campbell A, Arteta M, Gladwin MT, Castro O, Taylor JG 6th, Kato GJ, Gordeuk V. Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia. J Pediatr. 2012;160:286–90. [PMC free article: PMC3258348] [PubMed: 21890147]

  • DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014;371:699–710. [PMC free article: PMC4195437] [PubMed: 25140956]

  • DeBaun MR, Kirkham FJ. Central nervous system complications and management in sickle cell disease. Blood. 2016;127:829–38. [PubMed: 26758917]

  • De Castro LM, Jonassaint JC, Graham FL, Ashley-Koch A, Telen MJ. Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes. Am J Hematol. 2008;83:19–25. [PubMed: 17724699]

  • de Montalembert M. To SWiTCH or not to SWiTCH? Blood. 2012;119:3870–1. [PubMed: 22538492]

  • Dulmovits BM, Appiah-Kubi AO, Papoin J, Hale J, He M, Al-Abed Y, Didier S, Gould M, Husain-Krautter S, Singh SA, Chan KW, Vlachos A, Allen SL, Taylor N, Marambaud P, An X, Gallagher PG, Mohandas N, Lipton JM, Liu JM, Blanc L. Pomalidomide reverses γ-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors. Blood. 2016;127:1481–92. [PMC free article: PMC4797024] [PubMed: 26679864]

  • Ellison AM, Thurm C, Alessandrini E, Jain S, Cheng J, Black K, Schroeder L, Stone K, Alpern ER. Variation in pediatric emergency department care of sickle cell disease and fever. Acad Emerg Med. 2015;22:423–30. [PubMed: 25779022]

  • Estcourt LJ, Fortin PM, Hopewell S, Trivella M, Doree C, Abboud MR. Interventions for preventing silent cerebral infarcts in people with sickle cell disease. Cochrane Database Syst Rev. 2017;5:CD012389. [PMC free article: PMC5460750] [PubMed: 28500860]

  • Field JJ, Lin G, Okam MM, Majerus E, Keefer J, Onyekwere O, Ross A, Campigotto F, Neuberg D, Linden J, Nathan DG. Sickle cell vaso-occlusion causes activation of iNKT cells that is decreased by the adenosine A2A receptor agonist regadenoson. Blood. 2013;121:3329–34. [PMC free article: PMC3637009] [PubMed: 23377438]

  • Fitzhugh CD, Lauder N, Jonassaint JC, Telen MJ, Zhao X, Wright EC, Gilliam FR, De Castro LM. Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am J Hematol. 2010;85:36–40. [PMC free article: PMC3865703] [PubMed: 20029950]

  • Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A, Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med. 2021;384:252–60. [PubMed: 33283989]

  • Fullerton HJ, Adams RJ, Zhao S, Johnston SC. Declining stroke rates in Californian children with sickle cell disease. Blood. 2004;104:336–9. [PubMed: 15054044]

  • Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS, Diamond S, Tate Holbrook C, Gill FM, Ritchey K, Falletta JM., Prophylactic Penicillin Study Group. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med. 1986;314:1593–9. [PubMed: 3086721]

  • Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, Taubert KA. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119:1541–51. [PubMed: 19246689]

  • Gill FM, Sleeper LA, Weiner SJ, Brown AK, Bellevue R, Grover R, Pegelow CH, Vichinsky E. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood. 1995;86:776–83. [PubMed: 7606007]

  • Gladwin MT, Rodgers GP. Pathogenesis and treatment of acute chest syndrome of sickle-cell anaemia. Lancet. 2000;355:1476–8. [PubMed: 10801164]

  • Gluckman E. Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2013;2013:370–6. [PubMed: 24319206]

  • Goldsmith JC, Bonham VL, Joiner CH, Kato GJ, Noonan AS, Steinberg MH. Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications. Am J Hematol. 2012;87:340–6. [PMC free article: PMC3513289] [PubMed: 22307997]

  • Goodman MA, Malik P. The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges. Ther Adv Hematol. 2016;7:302–15. [PMC free article: PMC5026290] [PubMed: 27695619]

  • Harteveld CL, Voskamp A, Phylipsen M, Akkermans N, den Dunnen JT, White SJ, Giordano PC. Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterised by high resolution multiplex ligation-dependent probe amplification. J Med Genet. 2005;42:922–31. [PMC free article: PMC1735959] [PubMed: 15894596]

  • Hassell K. Pregnancy and sickle cell disease. Hematol Oncol Clin North Am. 2005;19:903–16. [PubMed: 16214651]

  • Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38:S512–21. [PubMed: 20331952]

  • Hassell KL, Afenyi-Annan A, Ballas SK, Buchanan GR, Eckman JR, Jordan L, Lanzkron S, Lottenberg R, Ware R. Practice guideline for pulmonary hypertension in sickle cell: direct evidence needed before universal adoption. Am J Respir Crit Care Med. 2014;190:237–8. [PubMed: 25025359]

  • Hebbel RP. Blockade of adhesion of sickle cells to endothelium by monoclonal antibodies. N Engl J Med. 2000;342:1910–2. [PubMed: 10861330]

  • Hebbel RP. Reconstructing sickle cell disease: a data-based analysis of the "hyperhemolysis paradigm" for pulmonary hypertension from the perspective of evidence-based medicine. Am J Hematol. 2011;86:123–54. [PubMed: 21264896]

  • Hebson C, New T, Record E, Oster M, Ehrlich A, Border W, James-Herry A, Kanaan U. Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in children with sickle cell disease: less prevalent and predictive than previously thought? J Pediatr Hematol Oncol. 2015;37:134–9. [PubMed: 24942020]

  • Jordan LC, Casella JF, DeBaun MR. Prospects for primary stroke prevention in children with sickle cell anaemia. Br J Haematol. 2012;157:14–25. [PMC free article: PMC3400704] [PubMed: 22224940]

  • Kassim AA, DeBaun MR. Sickle cell disease, vasculopathy, and therapeutics. Annu Rev Med. 2013;64:451–66. [PubMed: 23190149]

  • Kato GJ, McGowan V, Machado RF, Little JA, Taylor J 6th, Morris CR, Nichols JS, Wang X, Poljakovic M, Morris SM Jr, Gladwin MT. 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;107:2279–85. [PMC free article: PMC1895723] [PubMed: 16291595]

  • Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127:750–60. [PMC free article: PMC5330745] [PubMed: 28248201]

  • Kato GJ, Taylor JG 6th. Pleiotropic effects of intravascular haemolysis on vascular homeostasis. Br J Haematol. 2010;148:690–701. [PMC free article: PMC3210728] [PubMed: 19958359]

  • Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15:321–34. [PubMed: 24690881]

  • King A, Shenoy S. Evidence-based focused review of the status of hematopoietic stem cell transplantation as treatment of sickle cell disease and thalassemia. Blood. 2014;123:3089–94. [PubMed: 24511087]

  • Klings ES, Machado RF, Morris CR, Gordeuk VR, Kato GJ, Ataga KI, Castro O, Hsu L, Telen MJ, Krishnamurti L, Steinberg MH, Gladwin MT., ATS Clinical Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension in Sickle Cell Disease Committee. Reply: Practice Guideline for Pulmonary Hypertension in Sickle Cell: Direct Evidence Needed before Universal Adoption. Am J Respir Crit Care Med. 2014a;190:238–40. [PMC free article: PMC4226058] [PubMed: 25025360]

  • Klings ES, Morris CR, Hsu LL, Castro O, Gladwin MT, Mubarak KK. Pulmonary hypertension of sickle cell disease beyond classification constraints. J Am Coll Cardiol. 2014b;63:2881–2. [PubMed: 24794120]

  • Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematology Am Soc Hematol Educ Program. 2001:47–61. [PubMed: 11722978]

  • Lasalle-Williams M, Nuss R, Le T, Cole L, Hassell K, Murphy JR, Ambruso DR. Extended red blood cell antigen matching for transfusions in sickle cell disease: a review of a 14-year experience from a single center [CME]. Transfusion. 2011;51:1732–9. [PubMed: 21332724]

  • Lederman HM, Connolly MA, Kalpatthi R, Ware RE, Wang WC, Luchtman-Jones L, Waclawiw M, Goldsmith JC, Swift A, Casella JF, et al. Immunologic effects of hydroxyurea in sickle cell anemia. Pediatrics. 2014;134:686–95. [PMC free article: PMC4179098] [PubMed: 25180279]

  • Lee MT, Small T, Khan MA, Rosenzweig EB, Barst RJ, Brittenham GM. Doppler-defined pulmonary hypertension and the risk of death in children with sickle cell disease followed for a mean of three years. Br J Haematol. 2009;146:437–41. [PMC free article: PMC3078564] [PubMed: 19563512]

  • Lettre G, Bauer DE. Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies. Lancet. 2016;387:2554–64. [PubMed: 27353686]

  • Liem RI, Nevin MA, Prestridge A, Young LT, Thompson AA. Functional capacity in children and young adults with sickle cell disease undergoing evaluation for cardiopulmonary disease. Am J Hematol. 2009;84:645–9. [PubMed: 19705433]

  • Macari ER, Lowrey CH. Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway. Blood. 2011;117:5987–97. [PMC free article: PMC3112042] [PubMed: 21464371]

  • Macari ER, Schaeffer EK, West RJ, Lowrey CH. Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells. Blood. 2013;121:830–9. [PMC free article: PMC3563366] [PubMed: 23223429]

  • Machado RF, Anthi A, Steinberg MH, Bonds D, Sachdev V, Kato GJ, Taveira-DaSilva AM, Ballas SK, Blackwelder W, Xu X, Hunter L, Barton B, Waclawiw M, Castro O, Gladwin MT, Investigators MSH. N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA. 2006;296:310–8. [PubMed: 16849664]

  • Manci EA, Culberson DE, Yang YM, Gardner TM, Powell R, Haynes J Jr, Shah AK, Mankad VN., Investigators of the Cooperative Study of Sickle Cell Disease. Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003;123:359–65. [PubMed: 14531921]

  • Matteocci A, Pierelli L. Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing. Vox Sang. 2014;106:197–208. [PubMed: 24117723]

  • Mekontso Dessap A, Deux JF, Abidi N, Lavenu-Bombled C, Melica G, Renaud B, Godeau B, Adnot S, Brochard L, Brun-Buisson C, Galacteros F, Rahmouni A, Habibi A, Maitre B. Pulmonary artery thrombosis during acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med. 2011;184:1022–9. [PubMed: 21836136]

  • Menzel S, Garner C, Gut I, Matsuda F, Yamaguchi M, Heath S, Foglio M, Zelenika D, Boland A, Rooks H, Best S, Spector TD, Farrall M, Lathrop M, Thein SL. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet. 2007;39:1197–9. [PubMed: 17767159]

  • Miller ST. How I treat acute chest syndrome in children with sickle cell disease. Blood. 2011;117:5297–305. [PubMed: 21406723]

  • Miller ST, Sleeper LA, Pegelow CH, Enos LE, Wang WC, Weiner SJ, Wethers DL, Smith J, Kinney TR. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000;342:83–9. [PubMed: 10631276]

  • Miller ST, Wright E, Abboud M, Berman B, Files B, Scher CD, Styles L, Adams RJ. STOP Investigators. Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial [STOP] in sickle-cell anemia. J Pediatr. 2001;139:785–9. [PubMed: 11743502]

  • Morris C, Vichinsky E, Styles L. Clinician assessment for acute chest syndrome in febrile patients with sickle cell disease: is it accurate enough? Ann Emerg Med. 1999;34:64–9. [PubMed: 10381996]

  • Morris CR, Kuypers FA, Lavrisha L, Ansari M, Sweeters N, Stewart M, Gildengorin G, Neumayr L, Vichinsky EP. A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica. 2013;98:1375–82. [PMC free article: PMC3762093] [PubMed: 23645695]

  • Morris CR, Suh JH, Hagar W, Larkin S, Bland DA, Steinberg MH, Vichinsky EP, Shigenaga M, Ames B, Kuypers FA, Klings ES. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. Blood. 2008b;111:402–10. [PMC free article: PMC2200820] [PubMed: 17848621]

  • Mousa SA, Qari MH. Diagnosis and management of sickle cell disorders. Methods Mol Biol. 2010;663:291–307. [PubMed: 20617425]

  • Nagel RL. Pleiotropic and epistatic effects in sickle cell anemia. Curr Opin Hematol. 2001;8:105–10. [PubMed: 11224685]

  • Naik RP, Irvin MR, Judd S, Gutiérrez OM, Zakai NA, Derebail VK, Peralta C, Lewis MR, Zhi D, Arnett D, McClellan W, Wilson JG, Reiner AP, Kopp JB, Winkler CA, Cushman M. Sickle cell trait and the risk of ESRD in blacks. J Am Soc Nephrol. 2017;28:2180–7. [PMC free article: PMC5491293] [PubMed: 28280138]

  • Naik RP, Lanzkron S. Baby on board: what you need to know about pregnancy in the hemoglobinopathies. Hematology Am Soc Hematol Educ Program. 2012;2012:208–14. [PubMed: 23233583]

  • Neville KA, Panepinto JA. Pharmacotherapy of sickle cell disease. 18th Expert Committee on the Selection and Use of Essential Medicines. Available online. 2011. Accessed 4-19-22.

  • NHS. Sickle cell disease in childhood: standards and guidelines for clinical care. Available online. 2010. Accessed 4-19-22.

  • Nickel RS, Hendrickson JE, Haight AE. The ethics of a proposed study of hematopoietic stem cell transplant for children with "less severe" sickle cell disease. Blood. 2014;124:861–6. [PubMed: 24963044]

  • Oder E, Safo MK, Abdulmalik O, Kato GJ. New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Br J Haematol. 2016;175:24–30. [PMC free article: PMC5035193] [PubMed: 27605087]

  • Okam MM, Ebert BL. Novel approaches to the treatment of sickle cell disease: the potential of histone deacetylase inhibitors. Expert Rev Hematol. 2012;5:303–11. [PubMed: 22780210]

  • Okusanya BO, Oladapo OT. Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy. Cochrane Database Syst Rev. 2016;12:CD010378. [PMC free article: PMC6463955] [PubMed: 28005272]

  • Oniyangi O, Cohall DH. Phytomedicines [medicines derived from plants] for sickle cell disease. Cochrane Database Syst Rev. 2015;[4]:CD004448. [PubMed: 25844571]

  • Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaïci A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365:44–53. [PubMed: 21732836]

  • Perrine SP, Pace BS, Faller DV. Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies. Hematol Oncol Clin North Am. 2014;28:233–48. [PubMed: 24589264]

  • Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med. 2008;358:1362–9. [PubMed: 18367739]

  • Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330:1639–44. [PubMed: 7993409]

  • Powars DR, Hiti A, Ramicone E, Johnson C, Chan L. Outcome in hemoglobin SC disease: a four-decade observational study of clinical, hematologic, and genetic factors. Am J Hematol. 2002;70:206–15. [PubMed: 12111766]

  • Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115:3447–52. [PMC free article: PMC2867259] [PubMed: 20194891]

  • Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chrétien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M. Gene therapy in a patient with sickle cell disease. N Engl J Med. 2017;376:848–855. [PubMed: 28249145]

  • Rogers ZR. Priapism in sickle cell disease. Hematol Oncol Clin North Am. 2005;19:917–28. [PubMed: 16214652]

  • Rogers ZR, Wang WC, Luo Z, Lyer RV, Shalaby-Rana E, Dertinger SD, Shulkin BL, Miller JH, Files B, Lane PA, Thompson BW, Miller ST, Ware RE. Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. Blood. 2011;117:2614–7. [PMC free article: PMC3062353] [PubMed: 21217080]

  • Sachdev V, Kato GJ, Gibbs JS, Barst RJ, Machado RF, Nouraie M, Hassell KL, Little JA, Schraufnagel DE, Krishnamurti L, Novelli EM, Girgis RE, Morris CR, Rosenzweig EB, Badesch DB, Lanzkron S, Castro OL, Taylor JG 6th, Hannoush H, Goldsmith JC, Gladwin MT, Gordeuk VR. Walk-PHASST Investigators. Echocardiographic markers of elevated pulmonary pressure and left ventricular diastolic dysfunction are associated with exercise intolerance in adults and adolescents with homozygous sickle cell anemia in the United States and United Kingdom. Circulation. 2011;124:1452–60. [PMC free article: PMC3183314] [PubMed: 21900080]

  • Sankaran VG, Menne TF, Xu J, Akie TE, Lettre G, Van Handel B, Mikkola HK, Hirschhorn JN, Cantor AB, Orkin SH. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008;322:1839–42. [PubMed: 19056937]

  • Sankaran VG, Xu J, Byron R, Greisman HA, Fisher C, Weatherall DJ, Sabath DE, Groudine M, Orkin SH, Premawardhena A, Bender MA. A functional element necessary for fetal hemoglobin silencing. N Engl J Med. 2011;365:807–14. [PMC free article: PMC3174767] [PubMed: 21879898]

  • Sankaran VG, Xu J, Orkin SH. Transcriptional silencing of fetal hemoglobin by BCL11A. Ann N Y Acad Sci. 2010;1202:64–8. [PubMed: 20712774]

  • Saunthararajah Y, Molokie R, Saraf S, Sidhwani S, Gowhari M, Vara S, Lavelle D, DeSimone J. Clinical effectiveness of decitabine in severe sickle cell disease. Br J Haematol. 2008;141:126–9. [PubMed: 18324975]

  • Scharenberg AM, Duchateau P, Smith J. Genome engineering with TAL-effector nucleases and alternative modular nuclease technologies. Curr Gene Ther. 2013;13:291–303. [PubMed: 23888878]

  • Schatz J, Brown RT, Pascual JM, Hsu L, DeBaun MR. Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease. Neurology. 2001;56:1109–11. [PubMed: 11320190]

  • Shi L, Cui S, Engel JD, Tanabe O. Lysine-specific demethylase 1 is a therapeutic target for fetal hemoglobin induction. Nat Med. 2013;19:291–4. [PMC free article: PMC5512162] [PubMed: 23416702]

  • Smith JA, Espeland M, Bellevue R, Bonds D, Brown AK, Koshy M. Pregnancy in sickle cell disease: experience of the Cooperative Study of Sickle Cell Disease. Obstet Gynecol. 1996;87:199–204. [PubMed: 8559523]

  • Steinberg MH. Predicting clinical severity in sickle cell anaemia. Br J Haematol. 2005;129:465–81. [PubMed: 15877729]

  • Steinberg MH, Adewoye AH. Modifier genes and sickle cell anemia. Curr Opin Hematol. 2006;13:131–6. [PubMed: 16567954]

  • Strouse JJ, Heeney MM. Hydroxyurea for the treatment of sickle cell disease: efficacy, barriers, toxicity, and management in children. Pediatr Blood Cancer. 2012;59:365–71. [PMC free article: PMC3374046] [PubMed: 22517797]

  • Tarini BA, Brooks MA, Bundy DG. A policy impact analysis of the mandatory NCAA sickle cell trait screening program. Health Serv Res. 2012;47:446–61. [PMC free article: PMC3288389] [PubMed: 22150647]

  • Thompson AA. Sickle cell trait testing and athletic participation: a solution in search of a problem? Hematology Am Soc Hematol Educ Program. 2013;2013:632–7. [PubMed: 24319243]

  • Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC, et al. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012;120:4304–10. [PMC free article: PMC3507142] [PubMed: 22915643]

  • Tisdale JF, Eapen M, Saccardi R. HCT for nonmalignant disorders. Biol Blood Marrow Transplant. 2013;19:S6–9. [PubMed: 23104188]

  • Vichinsky E. Emerging 'A' therapies in hemoglobinopathies: agonists, antagonists, antioxidants, and arginine. Hematology Am Soc Hematol Educ Program. 2012;2012:271–5. [PubMed: 23233591]

  • Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med. 1990;322:1617–21. [PubMed: 2342522]

  • Villers MS, Jamison MG, De Castro LM, James AH. Morbidity associated with sickle cell disease in pregnancy. Am J Obstet Gynecol. 2008;199:125.e1–5. [PubMed: 18533123]

  • Walters MC, De Castro LM, Sullivan KM, Krishnamurti L, Kamani N, Bredeson C, Neuberg D, Hassell KL, Farnia S, Campbell A, Petersdorf E. Indications and results of HLA-identical sibling hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2016;22:207–11. [PMC free article: PMC5031360] [PubMed: 26500093]

  • Wang WC, Gallagher DM, Pegelow CH, Wright EC, Vichinsky EP, Abboud MR, Moser FG, Adams RJ. Multicenter comparison of magnetic resonance imaging and transcranial Doppler ultrasonography in the evaluation of the central nervous system in children with sickle cell disease. J Pediatr Hematol Oncol. 2000;22:335–9. [PubMed: 10959904]

  • Wang WC, Oyeku SO, Luo Z, Boulet SL, Miller ST, Casella JF, Fish B, Thompson BW, Grosse SD, et al. Hydroxyurea is associated with lower costs of care of young children with sickle cell anemia. Pediatrics. 2013;132:677–83. [PMC free article: PMC4074648] [PubMed: 23999955]

  • Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW., BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial [BABY HUG]. Lancet. 2011;377:1663–72. [PMC free article: PMC3133619] [PubMed: 21571150]

  • Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet. 2017;390:311–323. [PubMed: 28159390]

  • Webb J, Kwiatkowski JL. Stroke in patients with sickle cell disease. Expert Rev Hematol. 2013;6:301–16. [PubMed: 23782084]

  • Wilber A, Hargrove PW, Kim YS, Riberdy JM, Sankaran VG, Papanikolaou E, Georgomanoli M, Anagnou NP, Orkin SH, Nienhuis AW, Persons DA. Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer. Blood. 2011;117:2817–26. [PMC free article: PMC3062294] [PubMed: 21156846]

  • Wood DK, Soriano A, Mahadevan L, Higgins JM, Bhatia SN. A biophysical indicator of vaso-occlusive risk in sickle cell disease. Sci Transl Med. 2012;4:123ra26. [PMC free article: PMC3633235] [PubMed: 22378926]

  • Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, Ippolito GC, Fujiwara Y, Ebert BL, Tucker PW, Orkin SH. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011;334:993–6. [PMC free article: PMC3746545] [PubMed: 21998251]

  • Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312:1033–48. [PubMed: 25203083]

  • Yazdanbakhsh K, Ware RE, Noizat-Pirenne F. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood. 2012;120:528–37. [PMC free article: PMC3401213] [PubMed: 22563085]

  • Zarrouk V, Habibi A, Zahar JR, Roudot-Thoraval F, Bachir D, Brun-Buisson C, Legrand P, Godeau B, Galacteros F, Lesprit P. Bloodstream infection in adults with sickle cell disease: association with venous catheters, Staphylococcus aureus, and bone-joint infections. Medicine [Baltimore]. 2006;85:43–8. [PubMed: 16523052]

  • Zhang D, Xu C, Manwani D, Frenette PS. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood. 2016;127:801–9. [PMC free article: PMC4760086] [PubMed: 26758915]

  • How is an individual affected by having two copies of the sickle cell trait?

    If both parents have sickle cell trait [HbAS] there is a one in four [25%] chance that any given child could be born with sickle cell anaemia. There is also a one in four chance that any given child could be completely unaffected. There is a one in two [50%] chance that any given child will get the sickle cell trait.

    Is the allele for hemoglobin dominant or recessive?

    Caused by mutations in one of the genes that encode the hemoglobin protein, the disease is inherited as an autosomal recessive trait.

    Would it ever be beneficial to have one copy of the sickle cell allele?

    The Hidden Benefits of HbS People who have one copy of the HbS allele and one copy of the HbA allele, or people like you with sickle cell trait, have greater resistance to malaria. The sickled blood cells make it more difficult for the malaria to get into the blood.

    How does Dr allisons work provide an example of natural selection in humans?

    Dr. Allison provides evidence that shows that, while the sickle cell allele is advantageous in one environment, it is not in another. In an environment where malaria is endemic, individuals who carry the sickle cell allele have a selective advantage because they are protected against malaria.

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