Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-19T16:06:44.096Z Has data issue: false hasContentIssue false

21 - Hemoglobin SC Disease and Hemoglobin C Disorders

from SECTION FIVE - SICKLE CELL DISEASE

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Martin H. Steinberg  and
Ronald L. Nagel
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
Get access

Summary

INTRODUCTION

HbC (HBB glu6lys), along with HbS (HBB glu6val) and HbE (HBB glu26lys), is one of the three most common hemoglobin variants in humankind. Its positive charge that allows it to bind the erythrocyte membrane, and perhaps other unique features of this variant, lead to loss of cell K+ and water, thereby increasing erythrocyte density. HbC disease, defined as homozygosity for the HbC gene, causes mild hemolytic anemia; simple heterozygosity for HbC (HbC trait, HbAC) is innocuous. In HbSC disease, in which the erythrocyte concentration of HbS and HbC is nearly equal, the dehydrated, dense erythrocyte accentuates the deleterious properties of HbS by producing a milieu favoring HbS polymerization. HbSC disease causes vasoocclusive disease and hemolytic anemia, albeit on average both less severe than found in sickle cell anemia (homozygosity for HbS). Like sickle cell anemia, the hematological and clinical features of HbSC disease are heterogeneous, but all of the complications that make sickle cell anemia notorious can be present; some even appear more often in HbSC disease.

HbC and HbC Disease

Origins, Selection, and Distribution of HbC

HbC, the second hemoglobin variant discovered, was described in 1950, and the first homozygous case was reported in 1953. The βC-globin gene contains a GAG→AAG transition and codes for lysine instead of glutamic acid. Shortly after its description in African Americans, HbC was found to be common in Africa.

Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 525 - 548
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Kan, YW, Dozy, AM. Evolution of the hemoglobin S and C genes in world populations. Science. 1980;209:388–391.CrossRefGoogle Scholar
Dacie, J.The Haemolytic Anaemias. 3 ed. Edinburgh: Churchill Livingstone; 1988.Google Scholar
Labie, D, Richin, C, Pagnier, J, Gentilini, M, Nagel, RL. Hemoglobins S and C in Upper Volta. Hum Genet. 1984;65:300–302.CrossRefGoogle Scholar
Daar, S, Hussain, HM, Gravell, D, Nagel, RL, Krishnamoorthy, R. Genetic epidemiology of HbS and HbC in Oman: multicentric origin for the βS gene. Am J Hematol. 2000; 39–46.3.0.CO;2-#>CrossRefGoogle Scholar
Agarwal, A, Guindo, A, Cissoko, Y, et al. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood. 2000;96(7):2358–2363.Google Scholar
Modiano, D, Luoni, G, Sirima, BS, et al. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature. 2001;414(6861):305–308.CrossRefGoogle ScholarPubMed
Rihet, P, Flori, L, Tall, F, Traore, AS, Fumoux, F. Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. Hum Mol Genet. 2004;13(1):1–6.CrossRefGoogle ScholarPubMed
Fairhurst, RM, Fujioka, H, Hayton, K, Collins, KF, Wellems, TE. Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state. Blood. 2003;101(8):3309–3315.CrossRefGoogle ScholarPubMed
Mockenhaupt, FP, Ehrhardt, S, Cramer, JP, et al. Hemoglobin C and resistance to severe malaria in Ghanaian children. J Infect Dis. 2004;190(5):1006–1009.CrossRefGoogle ScholarPubMed
Mockenhaupt, FP, Ehrhardt, S, Burkhardt, J, et al. Manifestation and outcome of severe malaria in children in northern Ghana. Am J Trop Med Hyg. 2004;71(2):167–172.Google ScholarPubMed
Hirsch, RE, Lin, MJ, Nagel, RL. The inhibition of hemoglobin C crystallization by hemoglobin F. J Biol Chem. 1988;263:5936–5939.Google ScholarPubMed
Hirsch, RE, Raventos-Suarez, C, Olson, JA, Nagel, RL. Ligand state of intraerythrocytic circulating Hb C crystals in homozygous CC patients. Blood. 1985;66:775–777.Google ScholarPubMed
Hirsch, RE, Lin, MJ, Vidugirus, GVA, Huang, SC, Friedman, JM, Nagel, RL. Conformational changes in oxyhemoglobin C (Glu β6→lys) detected by spectroscopic probing. J Biol Chem. 1996;271:372–375.CrossRefGoogle ScholarPubMed
Hirsch, RE, Witkowska, HE, Shafer, F, et al. HbC compound heterozygotes [HbC/Hb Riyadh and HbC/Hb N- Baltimore] with opposing effects upon HbC crystallization. Br J Haematol. 1997;97:259–265.CrossRefGoogle ScholarPubMed
Nagel, RL, Lin, MJ, Witkowska, HE, Fabry, ME, Bestak, M, Hirsch, RE. Compound heterozygosity for hemoglobin C and Korle-Bu: Moderate microcytic hemolytic anemia and acceleration of crystal formation. Blood. 1993;82:1907–1912.Google ScholarPubMed
Lawrence, C, Hirsch, RE, Fataliev, NA, Patel, S, Fabry, ME, Nagel, RL. Molecular interactions between Hb α-G Philadelphia, HbC, and HbS: Phenotypic implications for SC α-G Philadelphia disease. Blood. 1997;90(7):2819–2825.Google ScholarPubMed
Hirsch, RE, Juszczak, LJ, Fataliev, NA, Friedman, JM, Nagel, RL. Solution-active structural alterations in liganded hemoglobins C (β6 Glu → Lys) and S (β6 Glu → Val). J Biol Chem. 1999;274(20):13777–13782.CrossRefGoogle Scholar
Feeling-Taylor, AR, Yau, ST, Petsev, DN, Nagel, RL, Hirsch, RE, Vekilov, PG. Crystallization mechanisms of hemoglobin C in the R state. Biophys J. 2004;87(4):2621–2629.CrossRefGoogle ScholarPubMed
Hirsch, RE, Samuel, RE, Fataliev, NA, et al. Differential pathways in oxy and deoxy HbC aggregation/crystallization. Proteins. 2001;42(1):99–107.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Jensen, WN, Schoefield, RA, Agner, R. Clinical and necropsy findings in hemoglobin C disease. Blood. 1998;12:74–83.Google Scholar
Brugnara, C, Kopin, AS, Bunn, HF, Tosteson, DC. Regulation of cation content and cell volume in hemoglobin erythrocytes from patients with homozygous hemoglobin C disease. J Clin Invest. 1985;75:1608–1617.CrossRefGoogle ScholarPubMed
Brugnara, C, Kopin, AS, Bunn, HF, Tosteson, DC. Electrolyte composition and equilibrium in hemoglobin CC red blood cells. Trans Assoc Am Physicians. 1984;97:104–112.Google ScholarPubMed
Canessa, M, Splavins, A, Nagel, RL. Volume-dependent and NEM-stimulated K+Cl- transport is elevated in oxygenated SS SC and CC human cells. FEBS Lett. 1986;200:197–202.CrossRefGoogle Scholar
Lauf, PK, Theg, BE. A chloride dependent K+ flux induced by N-ethlymaleimide in genetically low K+ sheep and goat erythrocytes. Biochem Biophys Res Commun. 1980;92:1422–1428.CrossRefGoogle Scholar
Dunham, PB, Ellory, JC. Passive potassium transport in low potassium sheep red cells: dependence upon cell volume and chloride. J Physiol. 1981;318:511–530.CrossRefGoogle ScholarPubMed
Canessa, M, Fabry, ME, Blumenfeld, N, Nagel, R. A volume-stimulated Cl-dependent K+ efflux is highly expressed in young human red cells containing normal hemoglobin or Hb S. J Membr Biol. 1987;97:97–105.CrossRefGoogle ScholarPubMed
Romero-Garcia, C, Navarro, JL, Lam, H, et al. Hb A2-Manzanares or α2δ2 121 (GH4) Glu-Val, an unstable δ chain variant observed in a Spanish family. Hemoglobin. 1983;7:435–442.CrossRefGoogle Scholar
Fabry, ME, Romero, JR, Suzuka, SM, et al. Hemoglobin C in transgenic mice: Effect of HbC expression from founders to full mouse globin knockouts. Blood Cells Mol Dis. 2000;26(4):331–347.CrossRefGoogle ScholarPubMed
Romero, JR, Suzuka, SM, Nagel, RL, Fabry, ME. Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. Blood. 2004;103(6):2384–2390.CrossRefGoogle Scholar
Romero, JR, Suzuka, SM, Romero-Gonzalez, GV, Nagel, RL, Fabry, ME. K:Cl cotransport activity is inhibited by HCO3 in knockout mouse red cells expressing human hemoglobin C. Blood Cells Mol Dis. 2001;27(1):69–70.CrossRefGoogle Scholar
Motulsky, AG. Frequency of sickling disorders in US blacks. N Engl J Med. 1973;288:31–33.CrossRefGoogle Scholar
Lehmann, H, Huntsman, RG. Man's Haemoglobins. 2nd ed. Amsterdam: North Holland; 1974.Google Scholar
Hinchliffe, RF, Norcliffe, D, Farrar, LM, Lilleyman, JS. Mean cell haemoglobin concentration in subjects with haemoglobin C, D, E and S traits. Clin Lab Haematol. 1996;18:245–248.Google Scholar
Giordano, PC, Harteveld, CL, Michiels, JJ, et al. Atypical HbH disease in a Surinamese patient resulting from a combination of the -SEA and -α3.7 deletions with HbC heterozygosity. Br J Haematol. 1997;96:801–805.CrossRefGoogle Scholar
Liebhaber, SA, Cash, FE, Cornfield, DB. Evidence for posttranslational control of Hb C synthesis in an individual with Hb C trait and α-thalassemia. Blood. 1988;71:502–504.Google Scholar
Olson, JF, Ware, RE, Schultz, WH, Kinney, TR. Hemoglobin C disease in infancy and childhood. J Pediatr. 1994;125:745–747.CrossRefGoogle ScholarPubMed
Lin, MJ, Nagel, RL, Hirsch, RE. The acceleration of hemoglobin C crystallization by hemoglobin S. Blood. 1989;74:1823–1825.Google ScholarPubMed
Fabry, ME, Kaul, DK, Raventos-Suarez, C, Chang, H, Nagel, RL. SC cells have an abnormally high intracellular hemoglobin concentration: Pathophysiological consequences. J Clin Invest. 1982;70:1315–1319.CrossRefGoogle ScholarPubMed
Fabry, ME, Benjamin, L, Lawrence, C, Nagel, RL. An objective sign of painful crisis in sickle cell anemia. Blood. 1983;64:559–563.Google Scholar
Ballas, SK, Smith, ED. Red blood cell changes during the evolution of the sickle cell painful crisis. Blood. 1992;79:2154–2163.Google ScholarPubMed
Steinberg, MH, Nagel, RL, Lawrence, C, et al. β-globin gene haplotype in Hb SC disease. Am J Hematol. 1996;52:189–191.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Talacki, CA, Rappaport, E, Schwartz, E, Surrey, S, Ballas, SK. Beta-globin gene cluster haplotype in Hb C heterozygotes. Hemoglobin. 1990;14:229–240.CrossRefGoogle ScholarPubMed
Embury, SH, Hebbel, RP, Mohandas, N, Steinberg, MH. Sickle Cell Disease: Basic Principles and Clinical Practice. 1st ed. New York: Raven Press; 1994.Google Scholar
West, MS, Wethers, D, Smith, J, Steinberg, MH, Coop Study of Sickle Cell Disease. Laboratory profile of sickle cell disease: a cross-sectional analysis. J Clin Epidemiol. 1992;45:893–909.Google Scholar
Bannerman, RM, Serjeant, B, Seakins, M, England, JM, Serjeant, GR. Determinants of haemoglobin level in sickle cell-haemoglobin C disease. Br J Haematol. 1979;43:49–56.CrossRefGoogle ScholarPubMed
Serjeant, GR, Ashcroft, MT, Serjeant, BE. The clinical features of haemoglobin SC disease in Jamaica. Br J Haematol. 1973;24:491–501.CrossRefGoogle ScholarPubMed
Duits, AJ, Rodriguez, T, Schnog, JJ. Serum levels of angiogenic factors indicate a pro-angiogenic state in adults with sickle cell disease. Br J Haematol. 2006;134(1):116–119.CrossRefGoogle Scholar
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(3):206–215.CrossRefGoogle ScholarPubMed
Platt, OS, Rosenstock, W, Espeland, M. Influence of S hemoglobinopathies on growth and development. N Engl J Med. 1984;311:7–12.CrossRefGoogle ScholarPubMed
Stevens, MCG, Maude, GH, Cupidore, L, Jackson, H, Hayes, RJ, Serjeant, GR. Prepubertal growth and skeletal maturation in children with sickle cell disease. J Pediatr. 1986;78:124–132.Google ScholarPubMed
Leikin, SL, Gallagher, D, Kinney, TR, Sloane, D, Klug, P, Rida, W. Mortality in children and adolescents with sickle cell disease. Pediatrics. 1989;84:500–508.Google ScholarPubMed
Powars, D, Chan, LS, Schroeder, WA. The variable expression of sickle cell disease is genetically determined. Semin Hematol. 1990;27:360–376.Google ScholarPubMed
Platt, OS, Brambilla, DJ, Rosse, WF, et al. Mortality in sickle cell disease: Life expectancy and risk factors for early death. N Engl J Med. 1994;330:1639–1644.CrossRefGoogle ScholarPubMed
Koduri, PR, Agbemadzo, B, Nathan, S. Hemoglobin S-C disease revisited: clinical study of 106 adults. Am J Hematol. 2001;68(4):298–300.CrossRefGoogle ScholarPubMed
Bainbridge, R, Higgs, DR, Maude, GH, Serjeant, GR. Clinical presentation of homozygous sickle cell disease. J Pediatr. 1985;106:881–885.CrossRefGoogle ScholarPubMed
Welch, RB, Goldberg, MF. Sickle-cell hemoglobin and its relation to fundus abnormality. Arch Ophthalmol. 1966;75:353–362.CrossRefGoogle ScholarPubMed
Lutty, GA, Goldberg, MF. Ophthalmologic complications. In: Embury, SH, Hebbel, RP, Mohandas, N, Steinberg, MH, eds. Sickle Cell Disease: Basic Principles and Clinical Practice. 1st ed. New York: Raven; 1994:703–724.Google Scholar
McLeod, DS, Goldberg, MF, Lutty, GA. Dual-perspective analysis of vascular formations in sickle cell retinopathy. Arch Ophthalmol. 1993;111:1234–1245.CrossRefGoogle ScholarPubMed
Roy, MS, Gascon, P, Giuliani, D. Macular blood flow velocity in sickle cell disease: Relation to red cell density. Br J Ophthalmol. 1995;79:742–745.CrossRefGoogle ScholarPubMed
Lutty, GA, Merges, C, Crone, S, McLeod, DS. Immunohistochemical insights into sickle cell retinopathy. Curr Eye Res. 1994;13:125–138.CrossRefGoogle ScholarPubMed
Kim, SY, Mocanu, C, McLeod, DS et al. Expression of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in sickle cell retina and choroid. Exp Eye Res. 2003;77(4):433–445.CrossRefGoogle ScholarPubMed
McLeod, DS, Merges, C, Fukushima, A, Goldberg, MF, Lutty, GA. Histopathologic features of neovascularization in sickle cell retinopathy. Am J Ophthalmol. 1997;124(4):455–472.CrossRefGoogle ScholarPubMed
Mohan, JS, Lip, PL, Blann, AD, Bareford, D, Lip, GY. The angiopoietin/Tie-2 system in proliferative sickle retinopathy: relation to vascular endothelial growth factor, its soluble receptor Flt-1 and von Willebrand factor, and to the effects of laser treatment. Br J Ophthalmol. 2005;89(7):815–819.CrossRefGoogle ScholarPubMed
Lutty, GA, McLeod, DS, Pachnis, A, Costantini, F, Fabry, ME, Nagel, RL. Retinal and choroidal neovascularization in a transgenic mouse model of sickle cell disease. Am J Pathol. 1994;145:490–497.Google Scholar
Lutty, GA, Merges, C, McLeod, DS, et al. Nonperfusion of retina and choroid in transgenic mouse models of sickle cell disease. Curr Eye Res. 1998;17(4):438–444.CrossRefGoogle ScholarPubMed
Lutty, GA, Phelan, A, McLeod, DS, Fabry, ME, Nagel, RL. A rat model for sickle cell-mediated vaso-occlusion in retina. Microvasc Res. 1996;52:270–280.CrossRefGoogle ScholarPubMed
Lutty, GA, Taomoto, M, Cao, J, et al. Inhibition of TNF-alpha-induced sickle RBC retention in retina by a VLA-4 antagonist. Invest Ophthalmol Vis Sci. 2001;42(6):1349–1355.Google ScholarPubMed
Lutty, GA, Otsuji, T, Taomoto, M, et al. Mechanisms for sickle red blood cell retention in choroid. Curr Eye Res. 2002;25(3):163–171.CrossRefGoogle ScholarPubMed
Kunz, MM, McLeod, DS, Merges, C, Cao, J, Lutty, GA. Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy. Br J Ophthalmol. 2002;86(6):684–690.Google Scholar
Wajer, SD, Taomoto, M, McLeod, DS et al. Velocity measurements of normal and sickle red blood cells in the rat retinal and choroidal vasculatures. Microvasc Res. 2000;60(3):281–293.CrossRefGoogle ScholarPubMed
Penman, AD, Talbot, JF, Chuang, EL, Thomas, P, Serjeant, GR, Bird, AC. New classification of peripheral retinal vascular changes in sickle cell disease. Br J Ophthalmol. 1994;78:681–689.CrossRefGoogle ScholarPubMed
Talbot, JF, Bird, AC, Serjeant, GR, Hayes, RJ. Sickle cell retinopathy in young children in Jamaica. Br J Ophthalmol. 1982;66:149–154.CrossRefGoogle ScholarPubMed
Talbot, JF, Bird, AC, Maude, GH, Acheson, RW, Moriarity, BJ, Serjeant, GR. Sickle cell retinopathy in Jamaican children: further observations in a cohort study. Br J Ophthalmol. 1996;72:727–732.CrossRefGoogle Scholar
Kent, D, Arya, R, Aclimandos, WA, Bellingham, AJ, Bird, AC. Screening for ophthalmic manifestations of sickle cell disease in the United Kingdom. Eye. 1994;8:618–622.CrossRefGoogle ScholarPubMed
Raichand, M, Goldberg, MF, Nagpal, KC, Goldbaum, MH, Asdourian, GK. Evolution of neovascularization in sickle cell retinopathy: a prospective flourescein angiographic study. Arch Ophthalmol. 1977;95:1543–1552.CrossRefGoogle Scholar
Nagpal, KC, Patrianakos, D, Asdourian, GK, Goldberg, MF, Rabb, M, Jampol, L. Spontaneous regression (autoinfarction) of proliferative sickle retinopathy. Am J Ophthalmol. 1975;80:885–892.CrossRefGoogle ScholarPubMed
Goldberg, MF. Natural history of untreated proliferative sickle retinopathy. Arch Ophthalmol. 1971;85:428–437.CrossRefGoogle ScholarPubMed
Clarkson, JG. The ocular manifestations of sickle-cell disease: a prevalence and natural history study. Trans Am Ophthalmol Soc. 1992;90:481–504.Google ScholarPubMed
Condon, PI, Serjeant, GR. Behavior of untreated proliferative sickle retinopathy. Br J Ophthalmol. 1980;64:404–411.CrossRefGoogle ScholarPubMed
Fox, PD, Dunn, DT, Morris, JS, Serjeant, GR. Risk factors for proliferative sickle retinopathy. Br J Ophthalmol. 1990;74:172–176.CrossRefGoogle ScholarPubMed
Fox, PD, Vessey, S, Forshaw, ML, Serjeant, GR. Influence of genotype on the natural history of untreated proliferative sickle retinopathy – an angiographic study. Br J Ophthalmol. 1991;75:229–231.CrossRefGoogle ScholarPubMed
Downes, SM, Hambleton, IR, Chuang, EL, Lois, N, Serjeant, GR, Bird, AC. Incidence and natural history of proliferative sickle cell retinopathy: observations from a cohort study. Ophthalmology. 2005;112(11):1869–1875.CrossRefGoogle ScholarPubMed
Condon, PI, Serjeant, GR. Photocoagulation in proliferative sickle retinopathy: results of a 5-year study. Br J Ophthalmol. 1980;64:832–840.CrossRefGoogle ScholarPubMed
Farber, MD, Jampol, LM, Fox, P, et al. A randomized clinical trial of scatter photocoagulation of proliferative sickle retinopathy. Arch Ophthalmol. 1991;109:363–367.CrossRefGoogle Scholar
Platt, OS, Thorington, BD, Brambilla, DJ, et al. Pain in sickle cell disease – rates and risk factors. N Engl J Med. 1991;325:11–16.CrossRefGoogle ScholarPubMed
Castro, O, Brambilla, DJ, Thorington, B, et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. Blood. 1994;84:643–649.Google ScholarPubMed
Vichinsky, EP, Styles, , Colangelo, LH, et al. Acute chest syndrome in sickle cell disease: clinical presentation and course. Blood. 1997;89:1787–1792.Google ScholarPubMed
Gladwin, MT, Sachdev, V, Jison, ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350(9):886–895.CrossRefGoogle ScholarPubMed
Ataga, KI, Moore, CG, Jones, S, et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol. 2006;134(1):109–115.CrossRefGoogle ScholarPubMed
Taylor, JG, Ackah, D, Cobb, C, et al. Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease. Am J Hematol. 2008;83:6–14.CrossRefGoogle ScholarPubMed
Aquino, VM, Norvell, JM, Buchanan, GR. Acute splenic complications in children with sickle cell hemoglobin C disease. J Pediatr. 1997;130:961–965.CrossRefGoogle ScholarPubMed
Lane, PA, Rogers, ZR, Woods, GM, et al. Fatal pneumococcal septicemia in hemoglobin SC disease. J Pediatr. 1994; 124:859–862.CrossRefGoogle ScholarPubMed
Lane, PA, O'Connell, JL, Lear, JL, et al. Functional asplenia in hemoglobin SC disease. Blood. 1995;85(8):2238–2244.Google ScholarPubMed
Rogers, ZR, Buchanan, GR. Bacteremia in children with sickle hemoglobin C disease and sickle beta+-thalassemia: is prophylactic penicillin necessary?J Pediatr. 1995;127:348–354.CrossRefGoogle ScholarPubMed
Milner, PF, Kraus, AP, Sebes, JI, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med. 1991;325:1476–1481.CrossRefGoogle ScholarPubMed
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(5):570–578.CrossRefGoogle ScholarPubMed
Iyer, R, Baliga, R, Nagel, RL, et al. Maximum urine concentrating ability in children with Hb SC disease: effects of hydroxyurea. Am J Hematol. 2000;64(1):47–52.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Ballas, SK, Lewis, CN, Noone, AM, Krasnow, SH, Kamarulzaman, E, Burka, ER. Clinical hematological and biochemical features of Hb SC disease. Am J Hematol. 1982;13:37–51.CrossRefGoogle ScholarPubMed
Nolan, VG, Wyszynski, DF, Farrer, , Steinberg, MH. Hemolysis-associated priapism in sickle cell disease. Blood. 2005;106(9):3264–3267.CrossRefGoogle ScholarPubMed
Ohene-Frempong, K, Weiner, SJ, Sleeper, , et al. Cerebrovascular accidents in sickle cell disease: Rates and risk factors. Blood. 1998;91(1):288–294.Google ScholarPubMed
Koshy, M, Burd, L. Obstetric and Gynecologic Issues. In: Embury, SH, Hebbel, RP, Mohandas, N, Steinberg, MH, eds. Sickle Cell Disease: Basic Principles and Clinical Practice. 1st ed. New York: Lippincott-Raven; 1994:689–702.Google Scholar
Koshy, M, Burd, L, Wallace, D, Moawad, A, Baron, J. Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study. N Engl J Med. 1988;319:1447–1452.CrossRefGoogle ScholarPubMed
Serjeant, GR, Hambleton, I, Thame, M. Fecundity and pregnancy outcome in a cohort with sickle cell-haemoglobin C disease followed from birth. Br J Obstet Gynaecol. 2005; 112(9):1308–1314.CrossRefGoogle Scholar
Neumayr, L, Koshy, M, Haberkern, C, et al. Surgery in patients with hemoglobin SC disease. Am J Hematol. 1998;57(2):101–108.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Vichinsky, EP, Haberkern, CM, Neumayr, L, et al. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. N Engl J Med. 1995;333:206–213.CrossRefGoogle ScholarPubMed
Markham, MJ, Lottenberg, R, Zumberg, M. Role of phlebotomy in the management of hemoglobin SC disease: case report and review of the literature. Am J Hematol. 2003;73(2):121–125.CrossRefGoogle ScholarPubMed
Boehm, CD, Dowling, CE, Antonarakis, SE, Honig, GR, Kazazian, HH. Evidence supporting a single origin of the β(C)-globin gene in blacks. Am J Hum Genet. 1985;37:771–777.Google ScholarPubMed
Trabuchet, G, Elion, J, Dunda, O, et al. Nucleotide sequence evidence of the unicentric origin of the βC mutation in Africa. Hum Genet. 1991;87:597–601.CrossRefGoogle Scholar
Eaton, WA, Hofrichter, J. Sickle cell hemoglobin polymerization. Adv Protein Chem. 1990;40:63–280.CrossRefGoogle ScholarPubMed
Platt, OS, Brambilla, DJ, Rosse, WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330(23):1639–1644.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×