SpringerLink
Log in

Sickle Cell Disease

  • Chapter
  • First Online:
Stroke Genetics

  • 93 Accesses

Abstract

Sickle cell disease (SCD) is a monogenetic disease with a polygenic phenotype. Stroke and other cerebrovascular diseases are still among the most dramatic complications of SCD. The epidemiology of stroke in SCD differs from that of non-SCD associated stroke, creating a significant challenge with diagnosis and management. Further, a wide array of gene-gene and gene-environment interactions have been associated with stroke in SCD. All of these contribute to significant phenotypic variability both in the disease in general and specifically, the associated complications of stroke and cerebrovascular disease. More research is required to illuminate the biological complexity of SCD in general and the associated complication of stroke in particular.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Benson JM, Therrell BL Jr. History and current status of newborn screening for hemoglobinopathies. Semin Perinatol. 2010;34(2):134–44. https://doi.org/10.1053/j.semperi.2009.12.006.

    Article  PubMed  Google Scholar 

  2. Steinberg MH, Forget BG, Higgs DR, Weatherall DJ. Disorders of hemoglobin: genetics, pathophysiology, and clinical management. Cambridge University Press; 2009.

    Book  Google Scholar 

  3. Taylor JG, Tang DC, Savage SA, Leitman SF, Heller SI, Serjeant GR, et al. Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood. 2002;100(13):4303–9. https://doi.org/10.1182/blood-2001-12-0306.

    Article  CAS  PubMed  Google Scholar 

  4. Asare K, Gee BE, Stiles JK, Wilson NO, Driss A, Quarshie A, et al. Plasma interleukin-1β concentration is associated with stroke in sickle cell disease. Cytokine. 2010;49(1):39–44. https://doi.org/10.1016/j.cyto.2009.10.002.

    Article  CAS  PubMed  Google Scholar 

  5. Chang Milbauer L, Wei P, Enenstein J, Jiang A, Hillery CA, Scott JP, et al. Genetic endothelial systems biology of sickle stroke risk. Blood. 2008;111(7):3872–9. https://doi.org/10.1182/blood-2007-06-097188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hyacinth HI, Adams RJ, Voeks JH, Hibbert JM, Gee BE. Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk. Am J Hematol. 2014;89(1):47–51. https://doi.org/10.1002/ajh.23586.

    Article  CAS  PubMed  Google Scholar 

  7. Hyacinth HI, Gee BE, Adamkiewicz TV, Adams RJ, Kutlar A, Stiles JK, et al. Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia. Cytokine. 2012;60(1):302–8. https://doi.org/10.1016/j.cyto.2012.05.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hyacinth HI, Adams RJ, Greenberg CS, Voeks JH, Hill A, Hibbert JM, et al. Effect of chronic blood transfusion on biomarkers of coagulation activation and thrombin generation in sickle cell patients at risk for stroke. PLoS One. 2015;10(8):e0134193. https://doi.org/10.1371/journal.pone.0134193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ovbiagele B, Adams RJ. Trends in comorbid sickle cell disease among stroke patients. J Neurol Sci. 2012;313(1–2):86–91. https://doi.org/10.1016/j.jns.2011.09.023.

    Article  PubMed  Google Scholar 

  10. Ohene-Frempong K, Weiner SJ, Sleeper LA, Miller ST, Embury S, Moohr JW, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998;91(1):288–94.

    CAS  PubMed  Google Scholar 

  11. Verduzco LA, Nathan DG. Sickle cell disease and stroke. Blood. 2009;114(25):5117–25. https://doi.org/10.1182/blood-2009-05-220921.

    Article  CAS  PubMed  Google Scholar 

  12. Melo HA, Barreto-Filho JA, Prado RC, Cipolotti R. Transcranial Doppler in sickle cell anaemia: evaluation of brain blood flow parameters in children of Aracaju, Northeast-Brazil. Arq Neuropsiquiatr. 2008;66(2b):360–4.

    Article  PubMed  Google Scholar 

  13. Kassim AA, Pruthi S, Day M, Rodeghier M, Gindville MC, Brodsky MA, et al. Silent cerebral infarcts and cerebral aneurysms are prevalent in adults with sickle cell anemia. Blood. 2016;127(16):2038–40. https://doi.org/10.1182/blood-2016-01-694562.

    Article  CAS  PubMed  Google Scholar 

  14. Wang W, Enos L, Gallagher D, Thompson R, Guarini L, Vichinsky E, et al. Neuropsychologic performance in school-aged children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease. J Pediatr. 2001;139(3):391–7. https://doi.org/10.1067/mpd.2001.116935.

    Article  CAS  PubMed  Google Scholar 

  15. Prussien KV, Jordan LC, DeBaun MR, Compas BE. Cognitive function in sickle cell disease across domains, cerebral infarct status, and the lifespan: a meta-analysis. J Pediatr Psychol. 2019;44(8):948–58. https://doi.org/10.1093/jpepsy/jsz031.

    Article  PubMed  PubMed Central  Google Scholar 

  16. DeBaun MR, Armstrong FD, McKinstry RC, Ware RE, Vichinsky E, Kirkham FJ. Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia. Blood. 2012;119(20):4587–96. https://doi.org/10.1182/blood-2011-02-272682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kugler S, Anderson B, Cross D, Sharif Z, Sano M, Haggerty R, et al. Abnormal cranial magnetic resonance imaging scans in sickle-cell disease. Neurological correlates and clinical implications. Arch Neurol. 1993;50(6):629–35. https://doi.org/10.1001/archneur.1993.00540060059019.

    Article  CAS  PubMed  Google Scholar 

  18. Adams R, McKie V, Nichols F, Carl E, Zhang D-L, McKie K, et al. The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Engl J Med. 1992;326(9):605–10. https://doi.org/10.1056/NEJM199202273260905.

    Article  CAS  PubMed  Google Scholar 

  19. Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. 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(1):5–11. https://doi.org/10.1056/NEJM199807023390102.

    Article  CAS  PubMed  Google Scholar 

  20. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033–48.

    Article  PubMed  Google Scholar 

  21. Hankins JS, Fortner GL, McCarville MB, Smeltzer MP, Wang WC, Li CS, et al. The natural history of conditional transcranial Doppler flow velocities in children with sickle cell anaemia. Br J Haematol. 2008;142(1):94–9. https://doi.org/10.1111/j.1365-2141.2008.07167.x.

    Article  PubMed  Google Scholar 

  22. Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood. 2007;110(6):2166–72. https://doi.org/10.1182/blood-2006-12-061697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Quinn CT, Dowling MM. Cerebral tissue hemoglobin saturation in children with sickle cell disease. Pediatr Blood Cancer. 2012;59(5):881–7. https://doi.org/10.1002/pbc.24227.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fields ME, Guilliams KP, Ragan DK, Binkley MM, Eldeniz C, Chen Y, et al. Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease. Neurology. 2018;90(13):e1134–42. https://doi.org/10.1212/WNL.0000000000005194.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Guilliams KP, Fields ME, Dowling MM. Advances in understanding ischemic stroke physiology and the impact of vasculopathy in children with sickle cell disease. Stroke. 2019;50(2):266–73. https://doi.org/10.1161/STROKEAHA.118.020482.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ford AL, Ragan DK, Fellah S, Binkley MM, Fields ME, Guilliams KP, et al. Silent infarcts in sickle cell disease occur in the border zone region and are associated with low cerebral blood flow. Blood. 2018;132(16):1714–23. https://doi.org/10.1182/blood-2018-04-841247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Guilliams KP, Fields ME, Ragan DK, Chen Y, Eldeniz C, Hulbert ML, et al. Large-vessel vasculopathy in children with sickle cell disease: a magnetic resonance imaging study of infarct topography and focal atrophy. Pediatr Neurol. 2017;69:49–57. https://doi.org/10.1016/j.pediatrneurol.2016.11.005.

    Article  PubMed  Google Scholar 

  28. Fields ME, Guilliams KP, Ragan D, Binkley MM, Mirro A, Fellah S, et al. Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia. Blood. 2019;133(22):2436–44. https://doi.org/10.1182/blood-2018-09-876318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Guilliams KP, Fields ME, Ragan DK, Eldeniz C, Binkley MM, Chen Y, et al. Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia. Blood. 2018;131(9):1012–21. https://doi.org/10.1182/blood-2017-06-789842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Karkoska K, Quinn CT, Niss O, Pfeiffer A, Dong M, Vinks AA, et al. Hydroxyurea improves cerebral oxygen saturation in children with sickle cell anemia. Am J Hematol. 2021;96(5):538–44. https://doi.org/10.1002/ajh.26120.

  31. Nur E, Kim YS, Truijen J, van Beers EJ, Davis SC, Brandjes DP, et al. Cerebrovascular reserve capacity is impaired in patients with sickle cell disease. Blood. 2009;114(16):3473–8. https://doi.org/10.1182/blood-2009-05-223859.

    Article  CAS  PubMed  Google Scholar 

  32. Kim YS, Nur E, van Beers EJ, Truijen J, Davis SC, Biemond BJ, et al. Dynamic cerebral autoregulation in homozygous sickle cell disease. Stroke. 2009;40(3):808–14. https://doi.org/10.1161/strokeaha.108.531996.

    Article  PubMed  Google Scholar 

  33. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018–31. https://doi.org/10.1016/s0140-6736(10)61029-x.

    Article  CAS  PubMed  Google Scholar 

  34. Bunn HF, Nathan DG, Dover GJ, Hebbel RP, Platt OS, Rosse WF, et al. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010;116(5):687–92. https://doi.org/10.1182/blood-2010-02-268193.

    Article  CAS  PubMed  Google Scholar 

  35. Hoppe C, Klitz W, Cheng S, Apple R, Steiner L, Robles L, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103(6):2391–6. https://doi.org/10.1182/blood-2003-09-3015.

    Article  CAS  PubMed  Google Scholar 

  36. Tuder RM, Marecki JC, Richter A, Fijalkowska I, Flores S. Pathology of pulmonary hypertension. Clin Chest Med. 2007;28(1):23–42, vii. https://doi.org/10.1016/j.ccm.2006.11.010.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tobal R, Potjewijd J, Empel VPM, Ysermans R, Schurgers LJ, Reutelingsperger CP, et al. Vascular remodeling in pulmonary arterial hypertension: the potential involvement of innate and adaptive immunity. Front Med. 2021;8 https://doi.org/10.3389/fmed.2021.806899.

  38. Wang WC. The pathophysiology, prevention, and treatment of stroke in sickle cell disease. Curr Opin Hematol. 2007;14(3):191–7. https://doi.org/10.1097/MOH.0b013e3280ec5243.

    Article  PubMed  Google Scholar 

  39. Steinberg MH. Pathophysiologically based drug treatment of sickle cell disease. Trends Pharmacol Sci. 2006;27(4):204–10. https://doi.org/10.1016/j.tips.2006.02.007.

    Article  CAS  PubMed  Google Scholar 

  40. Joiner CH, Platt OS, Lux SE. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes. J Clin Invest. 1986;78(6):1487–96. https://doi.org/10.1172/jci112740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Connes P, Verlhac S, Bernaudin F. Advances in understanding the pathogenesis of cerebrovascular vasculopathy in sickle cell anaemia. Br J Haematol. 2013;161(4):484–98. https://doi.org/10.1111/bjh.12300.

    Article  CAS  PubMed  Google Scholar 

  42. Ito MT, da Silva Costa SM, Baptista LC, Carvalho-Siqueira GQ, Albuquerque DM, Rios VM, et al. Angiogenesis-related genes in endothelial progenitor cells may be involved in sickle cell stroke. J Am Heart Assoc. 2020;9(3):e014143. https://doi.org/10.1161/JAHA.119.014143.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hermann DM, Zechariah A. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. J Cereb Blood Flow Metab. 2009;29(10):1620–43. https://doi.org/10.1038/jcbfm.2009.100.

    Article  CAS  PubMed  Google Scholar 

  44. Lin K-C, Castro AC. Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents. Curr Opin Chem Biol. 1998;2(4):453–7. https://doi.org/10.1016/S1367-5931(98)80120-8.

    Article  CAS  PubMed  Google Scholar 

  45. Hebbel RP, Osarogiagbon R, Kaul D. The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation. 2004;11(2):129–51. https://doi.org/10.1080/10739680490278402.

    Article  CAS  PubMed  Google Scholar 

  46. Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol. 2009;84(9):618–25. https://doi.org/10.1002/ajh.21475.

    Article  CAS  PubMed Central  Google Scholar 

  47. Kato GJ, Martyr S, Blackwelder WC, Nichols JS, Coles WA, Hunter LA, et al. Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality. Br J Haematol. 2005;130(6):943–53. https://doi.org/10.1111/j.1365-2141.2005.05701.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Supanc V, Biloglav Z, Kes VB, Demarin V. Role of cell adhesion molecules in acute ischemic stroke. Ann Saudi Med. 2011;31(4):365–70. https://doi.org/10.4103/0256-4947.83217.

    Article  PubMed  PubMed Central  Google Scholar 

  49. El Husseini N, Bushnell C, Brown CM, Attix D, Rost NS, Samsa GP, et al. Vascular cellular adhesion molecule-1 (VCAM-1) and memory impairment in African-Americans after small vessel-type stroke. J Stroke Cerebrovasc Dis. 2020;29(4):104646. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104646.

    Article  PubMed  Google Scholar 

  50. Cui L-l, Nitzsche F, Pryazhnikov E, Tibeykina M, Tolppanen L, Rytkönen J, et al. Integrin α4 overexpression on rat mesenchymal stem cells enhances transmigration and reduces cerebral embolism after intracarotid injection. Stroke. 2017;48(10):2895–900. https://doi.org/10.1161/STROKEAHA.117.017809.

    Article  CAS  PubMed  Google Scholar 

  51. Gaston M, Smith J, Gallagher D, Flournoy-Gill Z, West S, Bellevue R, et al. Recruitment in the cooperative study of sickle cell disease (CSSCD). Control Clin Trials. 1987;8(4 Suppl):131S–40S. https://doi.org/10.1016/0197-2456(87)90016-x.

    Article  CAS  PubMed  Google Scholar 

  52. Hoppe C, Klitz W, D’Harlingue K, Cheng S, Grow M, Steiner L, et al. Confirmation of an association between the TNF(-308) promoter polymorphism and stroke risk in children with sickle cell anemia. Stroke. 2007;38(8):2241–6. https://doi.org/10.1161/strokeaha.107.483115.

    Article  CAS  PubMed  Google Scholar 

  53. Brown MD, Wick TM, Eckman JR. Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells. Pediatr Pathol Mol Med. 2001;20(1):47–72.

    Article  CAS  PubMed  Google Scholar 

  54. Jison ML, Munson PJ, Barb JJ, Suffredini AF, Talwar S, Logun C, et al. Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease. Blood. 2004;104(1):270–80. https://doi.org/10.1182/blood-2003-08-2760.

    Article  CAS  PubMed  Google Scholar 

  55. Iovannisci DM, Lammer EJ, Steiner L, Cheng S, Mahoney LT, Davis PH, et al. Association between a leukotriene C4 synthase gene promoter polymorphism and coronary artery calcium in young women: the Muscatine study. Arterioscler Thromb Vasc Biol. 2007;27(2):394–9. https://doi.org/10.1161/01.atv.0000252680.72734.10.

    Article  CAS  PubMed  Google Scholar 

  56. Davies CA, Loddick SA, Toulmond S, Stroemer RP, Hunt J, Rothwell NJ. The progression and topographic distribution of interleukin-1beta expression after permanent middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab. 1999;19(1):87–98. https://doi.org/10.1097/00004647-199901000-00010.

    Article  CAS  PubMed  Google Scholar 

  57. Sobowale OA, Parry-Jones AR, Smith CJ, Tyrrell PJ, Rothwell NJ, Allan SM. Interleukin-1 in stroke. Stroke. 2016;47(8):2160–7. https://doi.org/10.1161/STROKEAHA.115.010001.

    Article  PubMed  Google Scholar 

  58. Relton JK, Rothwell NJ. Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res Bull. 1992;29(2):243–6.

    Article  CAS  PubMed  Google Scholar 

  59. Garcia JH, Liu K-F, Relton JK. Interleukin-1 receptor antagonist decreases the number of necrotic neurons in rats with middle cerebral artery occlusion. Am J Pathol. 1995;147(5):1477.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Yamasaki Y, Matsuura N, Shozuhara H, Onodera H, Itoyama Y, Kogure K. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke. 1995;26(4):676–81.

    Article  CAS  PubMed  Google Scholar 

  61. Basu A, Lazovic J, Krady JK, Mauger DT, Rothstein RP, Smith MB, et al. Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. J Cereb Blood Flow Metab. 2005;25(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  62. Kuhlow CJ, Krady JK, Basu A, Levison SW. Astrocytic ceruloplasmin expression, which is induced by IL-1β and by traumatic brain injury, increases in the absence of the IL-1 type 1 receptor. Glia. 2003;44(1):76–84.

    Article  PubMed  Google Scholar 

  63. Rees DC, Gibson JS. Biomarkers in sickle cell disease. Br J Haematol. 2012;156(4):433–45. https://doi.org/10.1111/j.1365-2141.2011.08961.x.

    Article  CAS  PubMed  Google Scholar 

  64. Bernaudin F, Verlhac S, Freard F, Roudot-Thoraval F, Benkerrou M, Thuret I, et al. Multicenter prospective study of children with sickle cell disease: radiographic and psychometric correlation. J Child Neurol. 2000;15(5):333–43.

    Article  CAS  PubMed  Google Scholar 

  65. Jordan LC, Casella JF, DeBaun MR. Prospects for primary stroke prevention in children with sickle cell anaemia. Br J Haematol. 2012;157(1):14–25. https://doi.org/10.1111/j.1365-2141.2011.09005.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. England J, Rowan R, Dawson D, Lewis S, Shinton N, Stephens A, et al. Guidelines for haemoglobinopathy screening. Clin Lab Haematol. 1988;10(1):87–94.

    Article  Google Scholar 

  67. Stephens A, Baine R, Rucknagel D, Schneider R, Serjeant G. Recommendations for neonatal screening for haemoglobinopathies. Clin Lab Haematol. 1988;10(3):335–45.

    Article  Google Scholar 

  68. Clarke GM, Higgins TN. Laboratory investigation of hemoglobinopathies and thalassemias: review and update. Clin Chem. 2000;46(8):1284–90.

    Article  CAS  PubMed  Google Scholar 

  69. Prohovnik I, Pavlakis SG, Piomelli S, Bello J, Mohr JP, Hilal S, et al. Cerebral hyperemia, stroke, and transfusion in sickle cell disease. Neurology. 1989;39(3):344–8.

    Article  CAS  PubMed  Google Scholar 

  70. Pavlakis SG, Prohovnik I, Piomelli S, DeVivo DC. Neurologic complications of sickle cell disease. Adv Pediatr Infect Dis. 1989;36:247–76.

    CAS  Google Scholar 

  71. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–236.

    Article  PubMed  Google Scholar 

  72. Ganesalingam J, Redwood R, Jenkins I. Thrombolysis of an acute stroke presentation with an incidental unruptured aneurysm. JRSM Cardiovasc Dis. 2013;2:2048004013478808. https://doi.org/10.1177/2048004013478808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Majhadi L, Calvet D, Rosso C, Bartolucci P. Thrombolytic therapy for the treatment of acute ischaemic stroke in adults with homozygous sickle cell disease. BMJ Case Rep. 2017;2017 https://doi.org/10.1136/bcr-2017-220011.

  74. Adams RJ, Cox M, Ozark SD, Kanter J, Schulte PJ, **an Y, et al. Coexistent sickle cell disease has no impact on the safety or outcome of lytic therapy in acute ischemic stroke: findings from get with the guidelines-stroke. Stroke. 2017;48(3):686–91. https://doi.org/10.1161/strokeaha.116.015412.

    Article  PubMed  Google Scholar 

  75. Adams R, Aaslid R, el Gammal T, Nichols F, McKie V. Detection of cerebral vasculopathy in sickle cell disease using transcranial Doppler ultrasonography and magnetic resonance imaging. Case report. Stroke. 1988;19(4):518–20. https://doi.org/10.1161/01.str.19.4.518.

    Article  CAS  PubMed  Google Scholar 

  76. Adams RJ, Nichols FT, McKie VC, McKie KM, Stephens S, Carl E, et al. Transcranial Doppler: influence of hematocrit in children with sickle cell anemia without stroke. J Cardiovasc Technol. 1989;8(2):97–101.

    Google Scholar 

  77. Adams RJ, Nichols FT, Stephens S, Carl E, McKie VC, McKie K, et al. Transcranial Doppler: the influence of age and hematocrit in normal children. J Cardiovasc Ultrason. 1988;7(3):201–5.

    Google Scholar 

  78. Jeffries B, Lipper M, Kishore P. Major intracerebral arterial involvement in sickle cell disease. Surg Neurol. 1980;14(4):291–5.

    CAS  PubMed  Google Scholar 

  79. Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(2):517–84.

    Article  PubMed  Google Scholar 

  80. Adams RJ, Brambilla D, Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005;353(26):2769–78. https://doi.org/10.1056/NEJMoa050460.

    Article  CAS  PubMed  Google Scholar 

  81. Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial Doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016;387(10019):661–70. https://doi.org/10.1016/S0140-6736(15)01041-7.

    Article  CAS  PubMed  Google Scholar 

  82. DeBaun MR, Jordan LC, King AA, Schatz J, Vichinsky E, Fox CK, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020;4(8):1554–88. https://doi.org/10.1182/bloodadvances.2019001142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Cohen AR, Martin MB, Silber JH, Kim HC, Ohene-Frempong K, Schwartz E. A modified transfusion program for prevention of stroke in sickle cell disease. Blood. 1992;79(7):1657–61.

    Article  CAS  PubMed  Google Scholar 

  84. Russell MO, Goldberg HI, Hodson A, Kim HC, Halus J, Reivich M, et al. Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease. Blood. 1984;63(1):162–9.

    Article  CAS  PubMed  Google Scholar 

  85. Wang WC, Kovnar EH, Tonkin IL, Mulhern RK, Langston JW, Day SW, et al. High risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease. J Pediatr. 1991;118(3):377–82. https://doi.org/10.1016/s0022-3476(05)82150-x.

    Article  CAS  PubMed  Google Scholar 

  86. Wilimas J, Goff JR, Anderson HR Jr, Langston JW, Thompson E. Efficacy of transfusion therapy for one to two years in patients with sickle cell disease and cerebrovascular accidents. J Pediatr. 1980;96(2):205–8. https://doi.org/10.1016/s0022-3476(80)80803-1.

    Article  CAS  PubMed  Google Scholar 

  87. Scothorn DJ, Price C, Schwartz D, Terrill C, Buchanan GR, Shurney W, et al. Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke. J Pediatr. 2002;140(3):348–54. https://doi.org/10.1067/mpd.2002.122498.

    Article  PubMed  Google Scholar 

  88. Pegelow CH, Adams RJ, McKie V, Abboud M, Berman B, Miller ST, et al. Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. J Pediatr. 1995;126(6):896–9. https://doi.org/10.1016/s0022-3476(95)70204-0.

    Article  CAS  PubMed  Google Scholar 

  89. Hulbert ML, Scothorn DJ, Panepinto JA, Scott JP, Buchanan GR, Sarnaik S, et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J Pediatr. 2006;149(5):710–2. https://doi.org/10.1016/j.jpeds.2006.06.037.

    Article  PubMed  Google Scholar 

  90. Ware RE, Helms RW, Investigators SW. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH). Blood. 2012;119(17):3925–32. https://doi.org/10.1182/blood-2011-11-392340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Griessenauer CJ, Lebensburger JD, Chua MH, Fisher WS III, Hilliard L, Bemrich-Stolz CJ, et al. Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease. J Neurosurg Pediatr. 2015;16(1):64–73. https://doi.org/10.3171/2014.12.peds14522.

    Article  PubMed  Google Scholar 

  92. Kennedy BC, McDowell MM, Yang PH, Wilson CM, Li S, Hankinson TC, et al. Pial synangiosis for moyamoya syndrome in children with sickle cell anemia: a comprehensive review of reported cases. Neurosurg Focus. 2014;36(1):E12. https://doi.org/10.3171/2013.10.focus13405.

    Article  PubMed  Google Scholar 

  93. McGann PT, Ware RE. Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain? Curr Opin Hematol. 2011;18(3):158–65. https://doi.org/10.1097/MOH.0b013e32834521dd.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995;332(20):1317–22. https://doi.org/10.1056/NEJM199505183322001.

    Article  CAS  PubMed  Google Scholar 

  95. Kinney TR, Helms RW, O’Branski EE, Ohene-Frempong K, Wang W, Daeschner C, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94(5):1550–4.

    CAS  PubMed  Google Scholar 

  96. Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663–72. https://doi.org/10.1016/s0140-6736(11)60355-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nottage KA, Ware RE, Aygun B, Smeltzer M, Kang G, Moen J, et al. Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia. Br J Haematol. 2016;175(2):331–8. https://doi.org/10.1111/bjh.14235.

    Article  CAS  PubMed  Google Scholar 

  98. Heitzer AM, Longoria J, Okhomina V, Wang WC, Raches D, Potter B, et al. Hydroxyurea treatment and neurocognitive functioning in sickle cell disease from school age to young adulthood. Br J Haematol. 2021;195:256–66. https://doi.org/10.1111/bjh.17687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Partanen M, Kang G, Wang WC, Krull K, King AA, Schreiber JE, et al. Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease. Br J Haematol. 2020;189(6):1192–203. https://doi.org/10.1111/bjh.16519.

    Article  CAS  PubMed  Google Scholar 

  100. Karkoska K. Neuroprotection: further evidence for the early and universal use of hydroxyurea in children with sickle cell disease. Br J Haematol. 2021;195(2):158–9. https://doi.org/10.1111/bjh.17702.

    Article  CAS  PubMed  Google Scholar 

  101. Hyacinth HI, Idris IM. Cognitive deficit in sickle cell disease: is hydroxyurea part of the story? Br J Haematol. 2020;189(6):1014–5. https://doi.org/10.1111/bjh.16542.

    Article  PubMed  Google Scholar 

  102. Aygun B, Padmanabhan S, Paley C, Chandrasekaran V. Clinical significance of RBC alloantibodies and autoantibodies in sickle cell patients who received transfusions. Transfusion. 2002;42(1):37–43.

    Article  CAS  PubMed  Google Scholar 

  103. Chou ST, Alsawas M, Fasano RM, Field JJ, Hendrickson JE, Howard J, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327–55. https://doi.org/10.1182/bloodadvances.2019001143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Powars DR, Weiss JN, Chan LS, Schroeder WA. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood. 1984;63(4):921–6.

    Article  CAS  PubMed  Google Scholar 

  105. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330(23):1639–44. https://doi.org/10.1056/nejm199406093302303.

    Article  CAS  PubMed  Google Scholar 

  106. Hankins JS, Wynn LW, Brugnara C, Hillery CA, Li CS, Wang WC. Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia. Br J Haematol. 2008;140(1):80–5. https://doi.org/10.1111/j.1365-2141.2007.06884.x.

    Article  CAS  PubMed  Google Scholar 

  107. Brousseau DC, Scott JP, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, et al. A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood. 2015;126(14):1651–7. https://doi.org/10.1182/blood-2015-05-647107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Hankins J, Aygun B. Pharmacotherapy in sickle cell disease—state of the art and future prospects. Br J Haematol. 2009;145(3):296–308. https://doi.org/10.1111/j.1365-2141.2009.07602.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003;289(9):1136–42. https://doi.org/10.1001/jama.289.9.1136.

    Article  CAS  PubMed  Google Scholar 

  110. Aboursheid T, Albaroudi O, Alahdab F. Inhaled nitric oxide for treating pain crises in people with sickle cell disease. Cochrane Database Syst Rev. 2022;7(7):Cd011808. https://doi.org/10.1002/14651858.CD011808.pub3.

    Article  PubMed  Google Scholar 

  111. Lopez BL, Kreshak AA, Morris CR, Davis-Moon L, Ballas SK, Ma XL. L-arginine levels are diminished in adult acute vaso-occlusive sickle cell crisis in the emergency department. Br J Haematol. 2003;120(3):532–4. https://doi.org/10.1046/j.1365-2141.2003.04109.x.

    Article  CAS  PubMed  Google Scholar 

  112. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005;294(1):81–90. https://doi.org/10.1001/jama.294.1.81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sullivan KJ, Kissoon N, Sandler E, Gauger C, Froyen M, Duckworth L, et al. Effect of oral arginine supplementation on exhaled nitric oxide concentration in sickle cell anemia and acute chest syndrome. J Pediatr Hematol Oncol. 2010;32(7):e249–58. https://doi.org/10.1097/MPH.0b013e3181ec0ae5.

    Article  CAS  PubMed  Google Scholar 

  114. Onalo R, Cilliers A, Cooper P, Morris CR. Arginine therapy and cardiopulmonary hemodynamics in hospitalized children with sickle cell anemia: a prospective, double-blinded, randomized placebo-controlled clinical trial. Am J Respir Crit Care Med. 2022;206(1):70–80. https://doi.org/10.1164/rccm.202108-1930OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Morris CR, Kuypers FA, Lavrisha L, Ansari M, Sweeters N, Stewart M, et al. 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(9):1375–82. https://doi.org/10.3324/haematol.2013.086637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Onalo R, Cooper P, Cilliers A, Vorster BC, Uche NA, Oluseyi OO, et al. Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in Nigeria. Am J Hematol. 2021;96(1):89–97. https://doi.org/10.1002/ajh.26028.

    Article  CAS  PubMed  Google Scholar 

  117. Canalli AA, Proenca RF, Franco-Penteado CF, Traina F, Sakamoto TM, Saad ST, et al. Participation of Mac-1, LFA-1 and VLA-4 integrins in the in vitro adhesion of sickle cell disease neutrophils to endothelial layers, and reversal of adhesion by simvastatin. Haematologica. 2011;96(4):526–33. https://doi.org/10.3324/haematol.2010.032912.

    Article  CAS  PubMed  Google Scholar 

  118. Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011;153(5):655–63. https://doi.org/10.1111/j.1365-2141.2010.08480.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Griffin TC, McIntire D, Buchanan GR. High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease. N Engl J Med. 1994;330(11):733–7. https://doi.org/10.1056/nejm199403173301101.

    Article  CAS  PubMed  Google Scholar 

  120. Walter O, Cougoul P, Maquet J, Bartolucci P, Lapeyre-Mestre M, Lafaurie M, et al. Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease. Blood. 2022;139(26):3771–7. https://doi.org/10.1182/blood.2021014473.

    Article  CAS  PubMed  Google Scholar 

  121. Ali MA, Ahmad A, Chaudry H, Aiman W, Aamir S, Anwar MY, et al. Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials. Exp Hematol. 2020;92:11–8.e1. https://doi.org/10.1016/j.exphem.2020.08.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Estepp JH, Kalpatthi R, Woods G, Trompeter S, Liem RI, Sims K, et al. Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years. Pediatr Blood Cancer. 2022;69:e29716. https://doi.org/10.1002/pbc.29716.

    Article  CAS  PubMed  Google Scholar 

  123. Shah N, Lipato T, Alvarez O, Delea T, Lonshteyn A, Weycker D, et al. Real-world effectiveness of voxelotor for treating sickle cell disease in the US: a large claims data analysis. Expert Rev Hematol. 2022;15(2):167–73. https://doi.org/10.1080/17474086.2022.2031967.

    Article  CAS  PubMed  Google Scholar 

  124. Muschick K, Fuqua T, Stoker-Postier C, Anderson AR. Real-world data on voxelotor to treat patients with sickle cell disease. Eur J Haematol. 2022;109:154–61. https://doi.org/10.1111/ejh.13782.

    Article  CAS  PubMed  Google Scholar 

  125. Rutherford-Parker NJ, Campbell ST, Colby JM, Shajani-Yi Z. Voxelotor treatment interferes with quantitative and qualitative hemoglobin variant analysis in multiple sickle cell disease genotypes. Am J Clin Pathol. 2020;154(5):627–34. https://doi.org/10.1093/ajcp/aqaa067.

    Article  CAS  PubMed  Google Scholar 

  126. Rutherford NJ, Thoren KL, Shajani-Yi Z, Colby JM. Voxelotor (GBT440) produces interference in measurements of hemoglobin S. Clin Chim Acta. 2018;482:57–9. https://doi.org/10.1016/j.cca.2018.03.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Payne AB, Schieve LA, Abe K, Hulihan M, Hooper WC, Hsu LL. COVID-19 and sickle cell disease-related deaths reported in the United States. Public Health Rep. 2022;137(2):234–8. https://doi.org/10.1177/00333549211063518.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Singh A, Brandow AM, Panepinto JA. COVID-19 in individuals with sickle cell disease/trait compared with other Black individuals. Blood Adv. 2021;5(7):1915–21. https://doi.org/10.1182/bloodadvances.2020003741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Lee JX, Chieng WK, Lau SCD, Tan CE. COVID-19 and hemoglobinopathies: a systematic review of clinical presentations, investigations, and outcomes. Front Med (Lausanne). 2021;8:757510. https://doi.org/10.3389/fmed.2021.757510.

    Article  PubMed  Google Scholar 

  130. Nachega JB, Sam-Agudu NA, Machekano RN, Rabie H, van der Zalm MM, Redfern A, et al. Assessment of clinical outcomes among children and adolescents hospitalized with COVID-19 in 6 sub-Saharan African countries. JAMA Pediatr. 2022;176(3):e216436. https://doi.org/10.1001/jamapediatrics.2021.6436.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Mucalo L, Brandow AM, Dasgupta M, Mason SF, Simpson PM, Singh A, et al. Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease. Blood Adv. 2021;5(13):2717–24. https://doi.org/10.1182/bloodadvances.2021004288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Minniti CP, Zaidi AU, Nouraie M, Manwani D, Crouch GD, Crouch AS, et al. Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection. Blood Adv. 2021;5(1):207–15. https://doi.org/10.1182/bloodadvances.2020003456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Trafane LF, da Costa VA, da Silva Santos Duarte A, Zangirolami AB, Proenca-Modena JL, de Melo Campos P, et al. Low SARS-CoV-2 seroprevalence in a cohort of Brazilian sickle cell disease patients: possible effects of emphasis on social isolation for a population initially considered to be at very high risk. EJHaem. 2021;2:478–82. https://doi.org/10.1002/jha2.254.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Arlet JB, Lionnet F, Khimoud D, Joseph L, de Montalembert M, Morisset S, et al. Risk factors for severe COVID-19 in hospitalized sickle cell disease patients: a study of 319 patients in France. Am J Hematol. 2022;97(3):E86–e91. https://doi.org/10.1002/ajh.26432.

    Article  CAS  PubMed  Google Scholar 

  135. Cai J, Chen-Goodspeed A, Idowu M. Risk and protective factors for severe COVID-19 infection in a cohort of patients with sickle cell disease. J Investig Med. 2022;70:1243–6. https://doi.org/10.1136/jim-2021-002196.

    Article  PubMed  Google Scholar 

  136. Silva-Pinto AC, Santos-Oliveira L, Santos FLS, Kashima Haddad S, De Santis GC, do Tocantins Calado R. COVID-19 infection in sickle cell patients in a develo** country: a case series. Acta Haematol. 2022;145(1):1–4. https://doi.org/10.1159/000519028.

    Article  CAS  PubMed  Google Scholar 

  137. Yurtsever N, Nandi V, Ziemba Y, Shi PA. Prognostic factors associated with COVID-19 related severity in sickle cell disease. Blood Cells Mol Dis. 2021;92:102627. https://doi.org/10.1016/j.bcmd.2021.102627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Madany E, Okwan-Duodu D, Balbuena-Merle R, Hendrickson JE, Gibb DR. Potential implications of a type 1 interferon gene signature on COVID-19 severity and chronic inflammation in sickle cell disease. Front Med (Lausanne). 2021;8:679030. https://doi.org/10.3389/fmed.2021.679030.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Brousse V, Holvoet L, Pescarmona R, Viel S, Perret M, Visseaux B, et al. Low incidence of COVID-19 severe complications in a large cohort of children with sickle cell disease: a protective role for basal interferon-1 activation? Haematologica. 2021;106(10):2746–8. https://doi.org/10.3324/haematol.2021.278573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Dua M, Bello-Manga H, Carroll YM, Galadanci AA, Ibrahim UA, King AA, et al. Strategies to increase access to basic sickle cell disease care in low- and middle-income countries. Expert. Rev Hematol. 2022;15:333–44. https://doi.org/10.1080/17474086.2022.2063116.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Cincinnati, Cincinnati, OH, USA

    N. Abimbola Sunmonu & Kristine Karkoska

  2. Stroke Neurology Division, University Eminent Scholar, Charleston, SC, USA

    Robert J. Adams

  3. Whitaker Price Chair for Brain Health, Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH, USA

    Hyacinth I. Hyacinth

Authors
  1. N. Abimbola Sunmonu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert J. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristine Karkoska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyacinth I. Hyacinth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyacinth I. Hyacinth .

Editor information

Editors and Affiliations

  1. Royal Holloway University of London, Egham, Greater London, UK

    Pankaj Sharma

  2. Dept of Neurology, Mayo Clinic, Jacksonville, FL, USA

    James F. Meschia

Rights and permissions

Reprints and permissions

Copyright information

© 2024 Mayo Clinic, The Editor(s) and The Author(s), under exclusive licence to Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sunmonu, N.A., Adams, R.J., Karkoska, K., Hyacinth, H.I. (2024). Sickle Cell Disease. In: Sharma, P., Meschia, J.F. (eds) Stroke Genetics. Springer, Cham. https://doi.org/10.1007/978-3-031-41777-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-41777-1_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-41776-4

  • Online ISBN: 978-3-031-41777-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation