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Overview of the clinical manifestations of sickle cell disease

Author
Elliott P Vichinsky, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

The sickle point mutation in the beta globin gene results in the production of sickle hemoglobin, which is less soluble than normal fetal or adult hemoglobin. Sickle cell disease (SCD) refers to any one of the syndromes in which the sickle mutation is co-inherited with a mutation at the other beta globin allele that reduces or abolishes normal beta globin production. These include sickle cell anemia (homozygous sickle mutation), sickle beta thalassemia, hemoglobin SC disease, and others.

The clinical manifestations of SCD are protean. The major features are related to hemolytic anemia and vasoocclusion, which can lead to acute and chronic pain and tissue ischemia or infarction. Splenic infarction leads to functional hyposplenism early in life, which in turn increases the risk of infection. These complications have a major impact on morbidity and mortality.

This topic review presents an overview of the major clinical manifestations of SCD. Each of these is discussed in more detail in separate topic reviews mentioned herein.

General overviews of the pathophysiology, diagnosis, and management of SCD are also presented separately.

Pathophysiology – (See "Mechanisms of vasoocclusion in sickle cell disease" and "Clinical variability in sickle cell anemia" and "Sickle hemoglobin polymer: Structure and functional properties".)

                                            

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Literature review current through: Nov 2016. | This topic last updated: Mon Jul 11 00:00:00 GMT 2016.
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References
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  1. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet 2010; 376:2018.
  2. www.cdc.gov/ncbddd/sicklecell/index.html (Accessed on October 03, 2011).
  3. Treadwell M, Johnson S, Sisler I, et al. Self-efficacy and readiness for transition from pediatric to adult care in sickle cell disease. Int J Adolesc Med Health 2016; 28:381.
  4. Treadwell M, Telfair J, Gibson RW, et al. Transition from pediatric to adult care in sickle cell disease: establishing evidence-based practice and directions for research. Am J Hematol 2011; 86:116.
  5. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med 1991; 325:11.
  6. Bainbridge R, Higgs DR, Maude GH, Serjeant GR. Clinical presentation of homozygous sickle cell disease. J Pediatr 1985; 106:881.
  7. Brozović M, Davies SC, Brownell AI. Acute admissions of patients with sickle cell disease who live in Britain. Br Med J (Clin Res Ed) 1987; 294:1206.
  8. Smith WR, Penberthy LT, Bovbjerg VE, et al. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med 2008; 148:94.
  9. Alexander N, Higgs D, Dover G, Serjeant GR. Are there clinical phenotypes of homozygous sickle cell disease? Br J Haematol 2004; 126:606.
  10. Powars DR. Natural history of sickle cell disease--the first ten years. Semin Hematol 1975; 12:267.
  11. Dampier C, Setty BN, Eggleston B, et al. Vaso-occlusion in children with sickle cell disease: clinical characteristics and biologic correlates. J Pediatr Hematol Oncol 2004; 26:785.
  12. Jones S, Duncan ER, Thomas N, et al. Windy weather and low humidity are associated with an increased number of hospital admissions for acute pain and sickle cell disease in an urban environment with a maritime temperate climate. Br J Haematol 2005; 131:530.
  13. Yallop D, Duncan ER, Norris E, et al. The associations between air quality and the number of hospital admissions for acute pain and sickle-cell disease in an urban environment. Br J Haematol 2007; 136:844.
  14. Nolan VG, Zhang Y, Lash T, et al. Association between wind speed and the occurrence of sickle cell acute painful episodes: results of a case-crossover study. Br J Haematol 2008; 143:433.
  15. Hargrave DR, Wade A, Evans JP, et al. Nocturnal oxygen saturation and painful sickle cell crises in children. Blood 2003; 101:846.
  16. Setty BN, Stuart MJ, Dampier C, et al. Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology. Lancet 2003; 362:1450.
  17. Sidman JD, Fry TL. Exacerbation of sickle cell disease by obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1988; 114:916.
  18. Bernard AW, Venkat A, Lyons MS. Best evidence topic report. Full blood count and reticulocyte count in painful sickle crisis. Emerg Med J 2006; 23:302.
  19. Hassell KL, Eckman JR, Lane PA. Acute multiorgan failure syndrome: a potentially catastrophic complication of severe sickle cell pain episodes. Am J Med 1994; 96:155.
  20. Rogers ZR, Wang WC, Luo Z, et al. Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. Blood 2011; 117:2614.
  21. Arzuza-Ortega L, Polo A, Pérez-Tatis G, et al. Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia. Emerg Infect Dis 2016; 22:925.
  22. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med 2000; 342:1855.
  23. Jacobs JE, Quirolo K, Vichinsky E. Novel influenza A (H1N1) viral infection in pediatric patients with sickle-cell disease. Pediatr Blood Cancer 2011; 56:95.
  24. Strouse JJ, Reller ME, Bundy DG, et al. Severe pandemic H1N1 and seasonal influenza in children and young adults with sickle cell disease. Blood 2010; 116:3431.
  25. McAuley CF, Webb C, Makani J, et al. High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya. Blood 2010; 116:1663.
  26. Halasa NB, Shankar SM, Talbot TR, et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2007; 44:1428.
  27. Overturf GD. Infections and immunizations of children with sickle cell disease. Adv Pediatr Infect Dis 1999; 14:191.
  28. Wong WY, Powars DR, Chan L, et al. Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty year epidemiologic experience. Am J Hematol 1992; 39:176.
  29. Williams TN, Uyoga S, Macharia A, et al. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet 2009; 374:1364.
  30. Hankins J, Ware RE. Sickle-cell disease: an ounce of prevention, a pound of cure. Lancet 2009; 374:1308.
  31. Greene JR, Polk OD, Castro O. Fulminant pneumococcal sepsis in an adult with sickle-cell anemia. N Engl J Med 1984; 311:674.
  32. Zarrouk V, Habibi A, Zahar JR, et al. Bloodstream infection in adults with sickle cell disease: association with venous catheters, Staphylococcus aureus, and bone-joint infections. Medicine (Baltimore) 2006; 85:43.
  33. Vichinsky E, Hurst D, Earles A, et al. Newborn screening for sickle cell disease: effect on mortality. Pediatrics 1988; 81:749.
  34. Makani J, Mgaya J, Balandya E, et al. Bacteraemia in sickle cell anaemia is associated with low haemoglobin: a report of 890 admissions to a tertiary hospital in Tanzania. Br J Haematol 2015.
  35. McCavit TL, Quinn CT, Techasaensiri C, Rogers ZR. Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure. J Pediatr 2011; 158:505.
  36. West MS, Wethers D, Smith J, Steinberg M. Laboratory profile of sickle cell disease: a cross-sectional analysis. The Cooperative Study of Sickle Cell Disease. J Clin Epidemiol 1992; 45:893.
  37. Sherwood JB, Goldwasser E, Chilcote R, et al. Sickle cell anemia patients have low erythropoietin levels for their degree of anemia. Blood 1986; 67:46.
  38. Vichinsky E, Kleman K, Embury S, Lubin B. The diagnosis of iron deficiency anemia in sickle cell disease. Blood 1981; 58:963.
  39. Embury SH, Dozy AM, Miller J, et al. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med 1982; 306:270.
  40. Saraf SL, Molokie RE, Nouraie M, et al. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatr Respir Rev 2014; 15:4.
  41. Lane PA, Rogers ZR, Woods GM, et al. Fatal pneumococcal septicemia in hemoglobin SC disease. J Pediatr 1994; 124:859.
  42. Pappo A, Buchanan GR. Acute splenic sequestration in a 2-month-old infant with sickle cell anemia. Pediatrics 1989; 84:578.
  43. Airede AI. Acute splenic sequestration in a five-week-old infant with sickle cell disease. J Pediatr 1992; 120:160.
  44. Emond AM, Collis R, Darvill D, et al. Acute splenic sequestration in homozygous sickle cell disease: natural history and management. J Pediatr 1985; 107:201.
  45. Smith-Whitley K, Zhao H, Hodinka RL, et al. Epidemiology of human parvovirus B19 in children with sickle cell disease. Blood 2004; 103:422.
  46. Topley JM, Rogers DW, Stevens MC, Serjeant GR. Acute splenic sequestration and hypersplenism in the first five years in homozygous sickle cell disease. Arch Dis Child 1981; 56:765.
  47. Orringer EP, Fowler VG Jr, Owens CM, et al. Case report: splenic infarction and acute splenic sequestration in adults with hemoglobin SC disease. Am J Med Sci 1991; 302:374.
  48. Piccin A, Smith OP, Murphy C, et al. Splenectomy in sickle cell anaemia: a cause of further crises? Br J Haematol 2009; 145:144.
  49. Petz LD, Calhoun L, Shulman IA, et al. The sickle cell hemolytic transfusion reaction syndrome. Transfusion 1997; 37:382.
  50. Talano JA, Hillery CA, Gottschall JL, et al. Delayed hemolytic transfusion reaction/hyperhemolysis syndrome in children with sickle cell disease. Pediatrics 2003; 111:e661.
  51. King KE, Shirey RS, Lankiewicz MW, et al. Delayed hemolytic transfusion reactions in sickle cell disease: simultaneous destruction of recipients' red cells. Transfusion 1997; 37:376.
  52. Cullis JO, Win N, Dudley JM, Kaye T. Post-transfusion hyperhaemolysis in a patient with sickle cell disease: use of steroids and intravenous immunoglobulin to prevent further red cell destruction. Vox Sang 1995; 69:355.
  53. Win N, New H, Lee E, de la Fuente J. Hyperhemolysis syndrome in sickle cell disease: case report (recurrent episode) and literature review. Transfusion 2008; 48:1231.
  54. Chadebech P, Habibi A, Nzouakou R, et al. Delayed hemolytic transfusion reaction in sickle cell disease patients: evidence of an emerging syndrome with suicidal red blood cell death. Transfusion 2009; 49:1785.
  55. Zimring JC, Spitalnik SL. To RBC or not to RBC: the role of suicidal death in hemolytic transfusion reactions. Transfusion 2009; 49:1776.
  56. de Montalembert M, Dumont MD, Heilbronner C, et al. Delayed hemolytic transfusion reaction in children with sickle cell disease. Haematologica 2011; 96:801.
  57. 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.
  58. Ballas SK, Marcolina MJ. Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia. Transfusion 2006; 46:105.
  59. Mota MA, Sakashita AM, Hammerschlak N, et al. Post-transfusion hyperhemolysis after haemolytic transfusion reaction in a patient with severe anemia: case report (abstract). Vox Sang 2006; 91:233.
  60. Win N, Sinha S, Lee E, Mills W. Treatment with intravenous immunoglobulin and steroids may correct severe anemia in hyperhemolytic transfusion reactions: case report and literature review. Transfus Med Rev 2010; 24:64.
  61. Bachmeyer C, Maury J, Parrot A, et al. Rituximab as an effective treatment of hyperhemolysis syndrome in sickle cell anemia. Am J Hematol 2010; 85:91.
  62. Akinbami AA, Dosunmu AO, Adediran AA, et al. Serum ferritin levels in adults with sickle cell disease in Lagos, Nigeria. J Blood Med 2013; 4:59.
  63. Rodrigues PC, Norton RC, Murao M, et al. Iron deficiency in Brazilian infants with sickle cell disease. J Pediatr (Rio J) 2011; 87:405.
  64. Sani MA, Adewuyi JO, Babatunde AS, et al. The Iron Status of Sickle Cell Anaemia Patients in Ilorin, North Central Nigeria. Adv Hematol 2015; 2015:386451.
  65. Kassim A, Thabet S, Al-Kabban M, Al-Nihari K. Iron deficiency in Yemeni patients with sickle-cell disease. East Mediterr Health J 2012; 18:241.
  66. Ali SB, Reid M, Fraser R, et al. Seizures in the Jamaica cohort study of sickle cell disease. Br J Haematol 2010; 151:265.
  67. Solh Z, Taccone MS, Marin S, et al. Neurological PRESentations in Sickle Cell Patients Are Not Always Stroke: A Review of Posterior Reversible Encephalopathy Syndrome in Sickle Cell Disease. Pediatr Blood Cancer 2016; 63:983.
  68. Lal A, Fung EB, Pakbaz Z, et al. Bone mineral density in children with sickle cell anemia. Pediatr Blood Cancer 2006; 47:901.
  69. Fitzhugh CD, Lauder N, Jonassaint JC, et al. Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am J Hematol 2010; 85:36.
  70. Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol 2012; 59:1123.
  71. Voskaridou E, Christoulas D, Terpos E. Sickle-cell disease and the heart: review of the current literature. Br J Haematol 2012; 157:664.
  72. Niss O, Quinn CT, Lane A, et al. Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease. JACC Cardiovasc Imaging 2016; 9:243.
  73. Poludasu S, Ramkissoon K, Salciccioli L, et al. Left ventricular systolic function in sickle cell anemia: a meta-analysis. J Card Fail 2013; 19:333.
  74. Knight-Perry JE, de Las Fuentes L, Waggoner AD, et al. Abnormalities in cardiac structure and function in adults with sickle cell disease are not associated with pulmonary hypertension. J Am Soc Echocardiogr 2011; 24:1285.
  75. Desai AA, Patel AR, Ahmad H, et al. Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy. Circ Cardiovasc Imaging 2014; 7:430.
  76. Covitz W, Espeland M, Gallagher D, et al. The heart in sickle cell anemia. The Cooperative Study of Sickle Cell Disease (CSSCD). Chest 1995; 108:1214.
  77. Zilberman MV, Du W, Das S, Sarnaik SA. Evaluation of left ventricular diastolic function in pediatric sickle cell disease patients. Am J Hematol 2007; 82:433.
  78. Johnson MC, Kirkham FJ, Redline S, et al. Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturation. Blood 2010; 116:16.
  79. Eddine AC, Alvarez O, Lipshultz SE, et al. Ventricular structure and function in children with sickle cell disease using conventional and tissue Doppler echocardiography. Am J Cardiol 2012; 109:1358.
  80. Westwood MA, Shah F, Anderson LJ, et al. Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy. J Magn Reson Imaging 2007; 26:564.
  81. Aessopos A, Farmakis D, Trompoukis C, et al. Cardiac involvement in sickle beta-thalassemia. Ann Hematol 2009; 88:557.
  82. Klings ES, Wyszynski DF, Nolan VG, Steinberg MH. Abnormal pulmonary function in adults with sickle cell anemia. Am J Respir Crit Care Med 2006; 173:1264.
  83. Balfour IC, Covitz W, Arensman FW, et al. Left ventricular filling in sickle cell anemia. Am J Cardiol 1988; 61:395.
  84. Sachdev V, Kato GJ, Gibbs JS, et al. 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.
  85. Gerry JL, Bulkley BH, Hutchins GM. Clinicopathologic analysis of cardiac dysfunction in 52 patients with sickle cell anemia. Am J Cardiol 1978; 42:211.
  86. Miller DM, Winslow RM, Klein HG, et al. Improved exercise performance after exchange transfusion in subjects with sickle cell anemia. Blood 1980; 56:1127.
  87. Martin CR, Johnson CS, Cobb C, et al. Myocardial infarction in sickle cell disease. J Natl Med Assoc 1996; 88:428.
  88. Pannu R, Zhang J, Andraws R, et al. Acute myocardial infarction in sickle cell disease: a systematic review. Crit Pathw Cardiol 2008; 7:133.
  89. Mueller BU, Martin KJ, Dreyer W, et al. Prolonged QT interval in pediatric sickle cell disease. Pediatr Blood Cancer 2006; 47:831.
  90. Liem RI, Young LT, Thompson AA. Prolonged QTc interval in children and young adults with sickle cell disease at steady state. Pediatr Blood Cancer 2009; 52:842.
  91. Graham JK, Mosunjac M, Hanzlick RL, Mosunjac M. Sickle cell lung disease and sudden death: a retrospective/prospective study of 21 autopsy cases and literature review. Am J Forensic Med Pathol 2007; 28:168.
  92. Machado RF, Mack AK, Martyr S, et al. Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease. Br J Haematol 2007; 136:319.
  93. Chacko P, Kraut EH, Zweier J, et al. Myocardial infarction in sickle cell disease: use of translational imaging to diagnose an under-recognized problem. J Cardiovasc Transl Res 2013; 6:752.
  94. Hurtova M, Bachir D, Lee K, et al. Transplantation for liver failure in patients with sickle cell disease: challenging but feasible. Liver Transpl 2011; 17:381.
  95. Mousa SM, El-Ghamrawy MK, Gouda H, et al. Prevalence of Hepatitis C among Egyptian Children with Sickle Cell Disease and the Role of IL28b Gene Polymorphisms in Spontaneous Viral Clearance. Mediterr J Hematol Infect Dis 2016; 8:e2016007.
  96. Diaku-Akinwumi IN, Abubakar SB, Adegoke SA, et al. Blood transfusion services for patients with sickle cell disease in Nigeria. Int Health 2016; 8:330.
  97. Namasopo SO, Ndugwa C, Tumwine JK. Hepatitis C and blood transfusion among children attending the Sickle Cell Clinic at Mulago Hospital, Uganda. Afr Health Sci 2013; 13:255.
  98. Hassan M, Hasan S, Giday S, et al. Hepatitis C virus in sickle cell disease. J Natl Med Assoc 2003; 95:939.
  99. Hassan M, Hasan S, Castro O, et al. HCV in sickle cell disease. J Natl Med Assoc 2003; 95:864.
  100. Ocak S, Kaya H, Cetin M, et al. Seroprevalence of hepatitis B and hepatitis C in patients with thalassemia and sickle cell anemia in a long-term follow-up. Arch Med Res 2006; 37:895.
  101. Wang Y, Kennedy J, Caggana M, et al. Sickle cell disease incidence among newborns in New York State by maternal race/ethnicity and nativity. Genet Med 2013; 15:222.
  102. Minniti CP, Delaney KM, Gorbach AM, et al. Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia. Am J Hematol 2014; 89:1.
  103. Eckman JR. Leg ulcers in sickle cell disease. Hematol Oncol Clin North Am 1996; 10:1333.
  104. Koshy M, Entsuah R, Koranda A, et al. Leg ulcers in patients with sickle cell disease. Blood 1989; 74:1403.
  105. Nolan VG, Adewoye A, Baldwin C, et al. Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. Br J Haematol 2006; 133:570.
  106. Ndiaye M, Niang SO, Diop A, et al. [Leg ulcers in sickle cell disease: A retrospective study of 40 cases]. Ann Dermatol Venereol 2016; 143:103.
  107. Cumming V, King L, Fraser R, et al. Venous incompetence, poverty and lactate dehydrogenase in Jamaica are important predictors of leg ulceration in sickle cell anaemia. Br J Haematol 2008; 142:119.
  108. Serjeant GR. Leg ulceration in sickle cell anemia. Arch Intern Med 1974; 133:690.
  109. Downes SM, Hambleton IR, Chuang EL, et al. Incidence and natural history of proliferative sickle cell retinopathy: observations from a cohort study. Ophthalmology 2005; 112:1869.
  110. Hayes RJ, Condon PI, Serjeant GR. Haematological factors associated with proliferative retinopathy in homozygous sickle cell disease. Br J Ophthalmol 1981; 65:29.
  111. Nagpal KC, Goldberg MF, Rabb MF. Ocular manifestations of sickle hemoglobinopathies. Surv Ophthalmol 1977; 21:391.
  112. Hayes RJ, Condon PI, Serjeant GR. Haematological factors associated with proliferative retinopathy in sickle cell-haemoglobin C disease. Br J Ophthalmol 1981; 65:712.
  113. Saidkasimova S, Shalchi Z, Mahroo OA, et al. Risk factors for visual impairment in patients with sickle cell disease in London. Eur J Ophthalmol 2016; 26:431.
  114. Cao J, Mathews MK, McLeod DS, et al. Angiogenic factors in human proliferative sickle cell retinopathy. Br J Ophthalmol 1999; 83:838.
  115. McLeod DS, Merges C, Fukushima A, et al. Histopathologic features of neovascularization in sickle cell retinopathy. Am J Ophthalmol 1997; 124:455.
  116. Friberg TR, Young CM, Milner PF. Incidence of ocular abnormalities in patients with sickle hemoglobinopathies. Ann Ophthalmol 1986; 18:150.
  117. Moriarty BJ, Acheson RW, Condon PI, Serjeant GR. Patterns of visual loss in untreated sickle cell retinopathy. Eye (Lond) 1988; 2 ( Pt 3):330.
  118. Myint KT, Sahoo S, Thein AW, et al. Laser therapy for retinopathy in sickle cell disease. Cochrane Database Syst Rev 2015; :CD010790.
  119. Farber MD, Jampol LM, Fox P, et al. A randomized clinical trial of scatter photocoagulation of proliferative sickle cell retinopathy. Arch Ophthalmol 1991; 109:363.
  120. Condon P, Jampol LM, Farber MD, et al. A randomized clinical trial of feeder vessel photocoagulation of proliferative sickle cell retinopathy. II. Update and analysis of risk factors. Ophthalmology 1984; 91:1496.
  121. Platt OS, Rosenstock W, Espeland MA. Influence of sickle hemoglobinopathies on growth and development. N Engl J Med 1984; 311:7.
  122. Stevens MC, Maude GH, Cupidore L, et al. Prepubertal growth and skeletal maturation in children with sickle cell disease. Pediatrics 1986; 78:124.
  123. Singhal A, Gabay L, Serjeant GR. Testosterone deficiency and extreme retardation of puberty in homozygous sickle-cell disease. West Indian Med J 1995; 44:20.
  124. Alleyne SI, Rauseo RD, Serjeant GR. Sexual development and fertility of Jamaican female patients with homozygous sickle cell disease. Arch Intern Med 1981; 141:1295.
  125. Kumar S, Powars D, Allen J, Haywood LJ. Anxiety, self-concept, and personal and social adjustments in children with sickle cell anemia. J Pediatr 1976; 88:859.
  126. Brandow AM, Brousseau DC, Panepinto JA. Postdischarge pain, functional limitations and impact on caregivers of children with sickle cell disease treated for painful events. Br J Haematol 2009; 144:782.
  127. Vichinsky EP, Neumayr LD, Gold JI, et al. Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia. JAMA 2010; 303:1823.
  128. Anie KA. Psychological complications in sickle cell disease. Br J Haematol 2005; 129:723.
  129. Panepinto JA, O'Mahar KM, DeBaun MR, et al. Health-related quality of life in children with sickle cell disease: child and parent perception. Br J Haematol 2005; 130:437.
  130. Dampier C, LeBeau P, Rhee S, et al. Health-related quality of life in adults with sickle cell disease (SCD): a report from the comprehensive sickle cell centers clinical trial consortium. Am J Hematol 2011; 86:203.
  131. Hogan AM, Kirkham FJ, Prengler M, et al. An exploratory study of physiological correlates of neurodevelopmental delay in infants with sickle cell anaemia. Br J Haematol 2006; 132:99.
  132. Dilworth-Anderson P. The importance of grandparents in extended-kin caregiving to black children with sickle cell disease. J Health Soc Policy 1994; 5:185.