Intravenous infusion of haptoglobin for the prevention of adverse clinical outcome in Sickle Cell Disease

Medical Hypotheses

Volumn 85, Issue 4, 2015, Pages 424-432

  Quimby, Kim R ^a   Hambleton, Ian R ^a   Landis, R Clive ^a  

^a UNIVERSITY OF THE WEST INDIES   (Jamaica)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; CD163 ANTIGEN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HAPTOGLOBIN; HEME OXYGENASE 1; HEMOGLOBIN; HEMOPEXIN; INTERLEUKIN 10; REACTIVE OXYGEN METABOLITE; ANTIINFLAMMATORY AGENT; BIOLOGICAL MARKER; CELL SURFACE RECEPTOR; DIFFERENTIATION ANTIGEN; HYDROXYUREA; IL10 PROTEIN, HUMAN; LEUKOCYTE ANTIGEN;

ALBUMINURIA; ARTICLE; BLOOD TRANSFUSION; BRAIN ISCHEMIA; CLINICAL TRIAL (TOPIC); COST CONTROL; CYTOKINE RELEASE; DRUG EFFICACY; ENZYME METABOLISM; GLOMERULUS FILTRATION RATE; HEALTH CARE COST; HEMOGLOBIN DETERMINATION; HEMOLYSIS; HUMAN; KIDNEY DISEASE; LEG ULCER; NONHUMAN; OXIDATION REDUCTION REACTION; PROTEIN EXPRESSION; PULMONARY HYPERTENSION; SICKLE CELL ANEMIA; UPREGULATION; WOUND CARE; ANEMIA, SICKLE CELL; CHILD; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; PRESCHOOL CHILD; THEORETICAL MODEL; TREATMENT OUTCOME;

ALBUMINURIA; ANEMIA, SICKLE CELL; ANTI-INFLAMMATORY AGENTS; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; BIOMARKERS; CHILD; CHILD, PRESCHOOL; HAPTOGLOBINS; HEMOGLOBINS; HEMOLYSIS; HEMOPEXIN; HUMANS; HYDROXYUREA; INFUSIONS, INTRAVENOUS; INTERLEUKIN-10; MODELS, THEORETICAL; REACTIVE OXYGEN SPECIES; RECEPTORS, CELL SURFACE; TREATMENT OUTCOME;

EID: 84942504675     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2015.06.023     Document Type: Article

References (105)

1. Pauling L. Molecular disease and evolution. Bull N Y Acad Med 1964 May, 40:334-342.
2. Ingram V.M. Abnormal human haemoglobins. III. The chemical difference between normal and sickle cell haemoglobins. Biochim Biophys Acta 1959 Dec, 36:402-411.
3. Pauling L., Itano H.A., Singer S.J., Wells I.C. Sickle cell anemia, a molecular disease. Science 1949 Nov, 25(110):543-548.
4. Herrick J.B. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med 1910 Nov 1, 6(VI):517-521.
5. Reiter C.D., Wang X., Tanus-Santos J.E., Hogg N., Cannon R.O., Schechter A.N., et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002 Dec, 8(12):1383-1389.
6. Bensinger T.A., Gillette P.N. Hemolysis in sickle cell disease. Arch Intern Med 1974 Apr, 133(4):624-631.
7. Rother R.P., Bell L., Hillmen P., Gladwin M.T. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005 Apr 6, 293(13):1653-1662.
8. Schaer D.J., Buehler P.W., Alayash A.I., Belcher J.D., Vercellotti G.M. Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood 2013 Feb 21, 121(8):1276-1284.
9. Jia Y., Buehler P.W., Boykins R.A., Venable R.M., Alayash A.I. Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway. J Biol Chem 2007 Feb 16, 282(7):4894-4907.
10. Gibson Q.H., Roughton F.J.W. The kinetics and equilibria of the reactions of nitric oxide with sheep haemoglobin. J Physiol 1957 May 23, 136(3):507-526.
11. Boretti F.S., Buehler P.W., D'Agnillo F., Kluge K., Glaus T., Butt O.I., et al. Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs. J Clin Invest 2009 Aug 3, 119(8):2271-2280.
12. Armstead V.E., Minchenko A.G., Schuhl R.A., Hayward R., Nossuli T.O., Lefer A.M. Regulation of P-selectin expression in human endothelial cells by nitric oxide. Am J Phys 1997 Aug 1, 273(2):H740-H746.
13. Radomski M.W., Palmer R.M., Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987 Nov 7, 2(8567):1057-1058.
14. Gladwin M.T., Sachdev V., Jison M.L., Shizukuda Y., Plehn J.F., Minter K., et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004 Feb 26, 350(9):886-895.
15. Kato G.J., McGowan V., Machado R.F., Little J.A., Taylor J., Morris C.R., et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006 Mar 15, 107(6):2279-2285.
16. Belcher J.D., Mahaseth H., Welch T.E., Otterbein L.E., Hebbel R.P., Vercellotti G.M. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J Clin Invest 2006 Mar, 116(3):808-816.
17. Clare A., FitzHenley M., Harris J., Hambleton I., Serjeant G.R. Chronic leg ulceration in homozygous sickle cell disease: the role of venous incompetence. Br J Haematol 2002 Nov, 119(2):567-571.
18. Hoover R., Rubin R., Wise G., Warren R. Adhesion of normal and sickle erythrocytes to endothelial monolayer cultures. Blood 1979 Oct, 54(4):872-876.
19. Radomski M.W., Palmer R.M., Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 1987 Nov 13, 148(3):1482-1489.
20. Hebbel R.P., Yamada O., Moldow C.F., Jacob H.S., White J.G., Eaton J.W. Abnormal adherence of sickle erythrocytes to cultured vascular endothelium: possible mechanism for microvascular occlusion in sickle cell disease. J Clin Invest 1980 Jan, 65(1):154-160.
21. Webb J., Kwiatkowski J.L. Stroke in patients with sickle cell disease. Exp Rev Hematol 2013 Jun 1, 6(3):301-316.
22. Hawker H., Neilson H., Hayes R.J., Serjeant G.R. Haematological factors associated with avascular necrosis of the femoral head in homozygous sickle cell disease. Br J Haematol 1982, 50(1):29-34.
23. Picot J., Goudot C., Berkenou J., Galacteros F., Colin Y., Bartolucci P., et al. Flow cytometry analyses reveal association between Lu/BCAM adhesion molecule and osteonecrosis in sickle cell disease. Am J Hematol 2014, 89(1):115-117.
24. Ataga K.I., Orringer E.P. Renal abnormalities in sickle cell disease. Am J Hematol 2000 Apr, 63(4):205-211.
25. Pham P.T., Pham P.C., Wilkinson A.H., Lew S.Q. Renal abnormalities in sickle cell disease. Kidney Int 2000 Jan, 57(1):1-8.
26. Guasch A., Navarrete J., Nass K., Zayas C.F. Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure. JASN 2006 Aug 1, 17(8):2228-2235.
27. King L., MooSang M., Miller M., Reid M. Prevalence and predictors of microalbuminuria in Jamaican children with sickle cell disease. Arch Dis Child 2011 Dec, 96(12):1135-1139.
28. Kristiansen M., Graversen J.H., Jacobsen C., Sonne O., Hoffman H.J., Law S.K., et al. Identification of the haemoglobin scavenger receptor. Nature 2001 Jan 11, 409(6817):198-201.
29. Otterbein L.E., Soares M.P., Yamashita K., Bach F.H. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 2003 Aug, 24(8):449-455.
30. Ryter S.W., Otterbein L.E., Morse D., Choi A.M.K. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 2002 Jun, 234-235(1-2):249-263.
31. Jison M.L., Munson P.J., Barb J.J., Suffredini A.F., 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 Jul 1, 104(1):270-280.
32. Baranano D.E., Rao M., Ferris C.D., Snyder S.H. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci USA 2002 Dec 10, 99(25):16093-16098.
33. Philippidis P., Mason J.C., Evans B.J., Nadra I., Taylor K.M., Haskard D.O., et al. Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circ Res 2004 Jan 9, 94(1):119-126.
34. Boyle J.J., Harrington H.A., Piper E., Elderfield K., Stark J., Landis R.C., et al. Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype. Am J Pathol 2009 Mar, 174(3):1097-1108.
35. Muller-Eberhard U., Javid J., Liem H.H., Hanstein A., Hanna M. Brief report: plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. Blood 1968 Nov 1, 32(5):811-815.
36. Quimby K.R., Fakunle E., Hambleton I., Landis R.C. Paradoxical inhibition of the haemoglobin scavenging mechanism in sickle cell disease. Br J Haematol 2011 Apr, 153(suppl. 1):40.
37. Thompson J., Reid M., Hambleton I., Serjeant G.R. Albuminuria and renal function in homozygous sickle cell disease: observations from a cohort study. Arch Intern Med 2007 Apr 9, 167(7):701-708.
38. Podmore A.H.B. Haptoglobin for the treatment of sickle cell disease. Biosci Hypotheses 2008, 1(1):59-63.
39. Adams R.J., McKie V.C., 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.
40. Yawn B.P., Buchanan G.R., Afenyi-Annan A.N., et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014 Sep 10, 312(10):1033-1048.
41. Wang W.C., Ware R.E., Miller S.T., Iyer R.V., Casella J.F., Minniti C.P., et al. A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia. Lancet 2011 May 14, 377(9778):1663-1672.
42. Thornburg C.D., Files B.A., Luo Z., Miller S.T., Kalpatthi R., Iyer R., et al. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood 2012 Nov 22, 120(22):4304-4310.
43. Laurin L.-P., Nachman P.H., Desai P.C., Ataga K.I., Derebail V.K. Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease. Nephrol Dial Transplant 2014 Jun, 29(6):1211-1218.
44. Silva Junior G.B., Vieira A.P.F., Couto Bem A.X., Alves M.P., Meneses G.C., Martins A.M.C., et al. Proteinuria in adults with sickle-cell disease: the role of hydroxycarbamide(hydroxyurea) as a protective agent. Int J Clin Pharm 2014 Aug, 36(4):766-770.
45. Falk R.J., Scheinman J., Phillips G., Orringer E., Johnson A., Jennette J.C. Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med 1992 Apr 2, 326(14):910-915.
46. Head C.A., Swerdlow P., McDade W.A., Joshi R.M., Ikuta T., Cooper M.L., et al. Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis. Am J Hematol 2010 Oct, 85(10):800-802.
47. Gladwin M.T.K.G. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA 2011 Mar 2, 305(9):893-902.
48. Coin J.T., Olson J.S. The rate of oxygen uptake by human red blood cells. J Biol Chem 1979 Feb 25, 254(4):1178-1190.
49. Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW. Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development. Front Physiol [Internet] 2014 Oct 28 [cited 2015 Mar 23];5. Available from: <>. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211382/.
50. Gando S., Tedo I. The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients. Surg Today 1994, 24(9):785-790.
51. Kanamori Y., Tanabe H., Shimono T., Tani K., Yada I., Yuasa H., et al. The effects of administration of haptoglobin for hemolysis by extracorporeal circulation. Rinsho Kyobu Geka 1989 Oct, 9(5):463-467.
52. Tanaka K., Kanamori Y., Sato T., Kondo C., Katayama Y., Yada I., et al. Administration of haptoglobin during cardiopulmonary bypass surgery. ASAIO Trans 1991 Sep, 37(3):M482-M483.
53. Hashimoto K., Nomura K., Nakano M., Sasaki T., Kurosawa H. Pharmacological intervention for renal protection during cardiopulmonary bypass. Heart Vessels 1993 Dec 1, 8(4):203-210.
54. Yoshioka T., Sugimoto T., Ukai T., Oshiro T. Haptoglobin therapy for possible prevention of renal failure following thermal injury: a clinical study. J Trauma 1985 Apr, 25(4):281-287.
55. Imaizumi H., Tsunoda K., Ichimiya N., Okamoto T., Namiki A. Repeated large-dose haptoglobin therapy in an extensively burned patient: case report. J Emerg Med 1994 Feb, 12(1):33-37.
56. Ohga S., Higashi E., Nomura A., Matsuzaki A., Hirono A., Miwa S., et al. Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara. Br J Haematol 1995 Feb, 89(2):421-423.
57. Horai T., Tanaka K., Takeda M. Coronary artery bypass grafting under cardiopulmonary bypass in a patient with beta-thalassemia: report of a case. Surg Today 2006, 36(6):538-540.
58. Tsuda H., Shirono K., Shimizu K. Is prophylactic haptoglobin infusion in peripheral blood stem cell transplantation clinically useful?. Eur J Haematol 1995 Sep, 55(3):214-215.
59. Yamamoto H., Nishikawa S., Yamazaki K., Kudo R. Efficacy of haptoglobin administration in the early postoperative course of patients with a diagnosis of HELLP syndrome. J Obstet Gynaecol 2000 Nov, 20(6):610-611.
60. Ito M., Imoto S., Nakagawa T., Kai S., Hara H. Administration of haptoglobin in ABO incompatible bone marrow transplantation. Rinsho Ketsueki 1990 Oct, 31(10):1716-1720.
61. Eda K., Ohtsuka S., Seo Y., Yamada S., Ishiyama M., Miyamoto T., et al. Conservative treatment of hemolytic complication following coil embolization in two adult cases of patent ductus arteriosus. Jpn Circ J 2001 Sep, 65(9):834-836.
62. Baek J.H., D'Agnillo F., Vallelian F., Pereira C.P., Williams M.C., Jia Y., et al. Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy. J Clin Invest 2012 Apr 2, 122(4):1444-1458.
63. Belcher J.D., Chen C., Nguyen J., Milbauer L., Abdulla F., Alayash A.I., et al. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 2014 Jan 16, 123(3):377-390.
64. Dalton J, Podmore A. Enriched haptoglobin polymers for the treatment of disease [Internet]. US20110021418 A1, 2011 [cited 2015 Mar 23]. Available from: <>. http://www.google.com/patents/US20110021418.
65. Bio Products Laboratory Ltd. Human haptoglobin for the treatment of sickle cell disease [Internet]. European Medicines Agency; 2011. Available from: <>. http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2011/12/WC500119799.pdf.
66. Langlois M.R., Delanghe J.R. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996 Oct, 42(10):1589-1600.
67. Koch W., Latz W., Eichinger M., Roguin A., Levy A.P., Schömig A., et al. Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR. Clin Chem 2002 Sep 1, 48(9):1377-1382.
68. Melamed-Frank M., Lache O., Enav B.I., Szafranek T., Levy N.S., Ricklis R.M., et al. Structure-function analysis of the antioxidant properties of haptoglobin. Blood 2001 Dec 15, 98(13):3693-3698.
69. Asleh R., Marsh S., Shilkrut M., Binah O., Guetta J., Lejbkowicz F., et al. Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circ Res 2003 Jun 13, 92(11):1193-1200.
70. Levy A.P., Levy J., Kalet-Litman S., Miller-Lotan R., Levy N., Asaf R., et al. Haptoglobin genotype is a determinant of iron, lipid peroxidation, and macrophage accumulation in the atherosclerotic plaque. Arterioscler Thromb Vasc Biol 2007, 27:134-140.
71. Levy A.P., Hochberg I., Jablonski K., Resnick H.E., Lee E.T., Best L., et al. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: the strong heart study. J Am Coll Cardiol 2002 Dec 4, 40(11):1984-1990.
72. Park K.U., Song J., Kim J.Q. Haptoglobin genotypic distribution (including Hp0 allele) and associated serum haptoglobin concentrations in Koreans. J Clin Pathol 2004 Oct, 57(10):1094-1095.
73. Lipiski M., Deuel J.W., Baek J.H., Engelsberger W.R., Buehler P.W., Schaer D.J. Human Hp1-1 and Hp2-2 phenotype-specific haptoglobin therapeutics are both effective in vitro and in guinea pigs to attenuate hemoglobin toxicity. Antioxid Redox Signal 2013 Nov 10, 19(14):1619-1633.
74. Buechler C., Ritter M., Orsó E., Langmann T., Klucken J., Schmitz G. Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. J Leukoc Biol 2000 Jan 1, 67(1):97-103.
75. Sulahian T.H., Högger P., Wahner A.E., Wardwell K., Goulding N.J., Sorg C., et al. Human monocytes express CD163, which is upregulated by IL-10 and identical to p155. Cytokine 2000 Sep, 12(9):1312-1321.
76. den Heuvel M.M.V., Tensen C.P., van As J.H., den Berg T.K.V., Fluitsma D.M., Dijkstra C.D., et al. Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation. J Leukoc Biol 1999 Nov 1, 66(5):858-866.
77. Ambarus C.A., Krausz S., van Eijk M., Hamann J., Radstake T.R.D.J., Reedquist K.A., et al. Systematic validation of specific phenotypic markers for in vitro polarized human macrophages. J Immunol Methods 2012 Jan 31, 375(1-2):196-206.
78. Hrkal Z., Vodrážka Z., Kalousek I. Transfer of heme from ferrihemoglobin and ferrihemoglobin isolated chains to hemopexin. Eur J Biochem 1974 Mar 1, 43(1):73-78.
79. Smith A., Hunt R.C. Hemopexin joins transferrin as representative members of a distinct class of receptor-mediated endocytic transport systems. Eur J Cell Biol 1990 Dec, 53(2):234-245.
80. Hvidberg V., Maniecki M.B., Jacobsen C., Højrup P., Møller H.J., Moestrup S.K. Identification of the receptor scavenging hemopexin-heme complexes. Blood 2005 Oct 1, 106(7):2572-2579.
81. Delanghe J.R., Langlois M.R. Hemopexin: a review of biological aspects and the role in laboratory medicine. Clin Chim Acta 2001 Oct, 312(1-2):13-23.
82. Vinchi F., Franceschi L.D., Ghigo A., Townes T., Cimino J., Silengo L., et al. Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation 2013 Mar 26, 127(12):1317-1329.
83. Foidart M., Liem H.H., Adornato B.T., Engel W.K., Muller-Eberhard U. Hemopexin metabolism in patients with altered serum levels. J Lab Clin Med 1983 Nov, 102(5):838-846.
84. Quimby K.R., Greenidge A., Harris A., Landis R.C. Phenotypic commitment of monocytes towards a protective hemoglobin scavenging phenotype (CD14(pos)CD163(high)HLA-DR(low))following cardiopulmonary bypass. Cytometry B 2010 Sep, 78(5):357-360.
85. Modell B., Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008 Jun, 86(6):480-487.
86. Kral M.C., Brown R.T., Hynd G.W. Neuropsychological aspects of pediatric sickle cell disease. Neuropsychol Rev 2001 Dec, 11(4):179-196.
87. Steen R.G., Miles M.A., Helton K.J., Strawn S., Wang W., Xiong X., et al. Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit. Am J Neuroradiol 2003 Mar 1, 24(3):382-389.
88. Ohene-Frempong K., Weiner S.J., Sleeper L.A., Miller S.T., Embury S., Moohr J.W., et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998 Jan 1, 91(1):288-294.
89. Stuart M.J., Nagel R.L. Sickle-cell disease. Lancet 2004 Oct 9, 364(9442):1343-1360.
90. Ebert E.C., Nagar M., Hagspiel K.D. Gastrointestinal and hepatic complications of sickle cell disease. Clin Gastroenterol Hepatol 2010 Jun, 8(6):483-489. quiz e70.
91. Di Sabatino A., Carsetti R., Corazza G.R. Post-splenectomy and hyposplenic states. Lancet 2011 Jul 2, 378(9785):86-97.
92. Ballas S.K., Lusardi M. Hospital readmission for adult acute sickle cell painful episodes: frequency, etiology, and prognostic significance. Am J Hematol 2005, 79(1):17-25.
93. Quimby K.R., Moe S., Sealy I., Nicholls C., Hambleton I.R., Landis R.C. Clinical findings associated with homozygous sickle cell disease in the Barbadian population - do we need a national SCD registry?. BMC Res Notes 2014 Feb, 22(7):102.
94. Bauer W.C., Rosenberc B.F. A quantitative study of glomerular enlargement in children with tetralogy of fallot. Am J Pathol 1960 Dec, 37(6):695-712.
95. Garcia D.L., Anderson S., Rennke H.G., Brenner B.M. Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass. PNAS 1988 Aug 1, 85(16):6142-6146.
96. Ataga K.I., Derebail V.K., Archer D.R. The glomerulopathy of sickle cell disease. Am J Hematol 2014, 89(9):907-914.
97. el-Hazmi M.A. Clinical and haematological diversity of sickle cell disease in Saudi children. J Trop Pediatr 1992 Jun, 38(3):106-112.
98. Dos Santos T.E.de J., Gonçalves R.P., Barbosa M.C., da Silva G.B., Daher E.D.F. Monocyte chemoatractant protein-1: A potential biomarker of renal lesion and its relation with oxidative status in sickle cell disease. Blood Cells Mol Dis 2014 Nov, 26.
99. Lance E.I., Casella J.F., Everett A.D., Barron-Casella E. Proteomic and biomarker studies and neurological complications of pediatric sickle cell disease. Proteomics Clin Appl 2014 Dec, 8(11-12):813-827.
100. Al-Humood S., Zueriq R., Al-Faris L., Marouf R., Al-Mulla F. Circulating cell-free DNA in sickle cell disease: is it a potentially useful biomarker?. Arch Pathol Lab Med 2014 May, 138(5):678-683.
101. Asnani M., Reid M. Cystatin C: a useful marker of glomerulopathy in sickle cell disease?. Blood Cells Mol Dis 2015 Jan, 54(1):65-70.
102. Wang WC, Dwan K. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 1996 [cited 2014 Dec 9]. Available from: <>. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003146.pub2/abstract.
103. Philip A.G. Haptoglobins in the newborn. I. Full-term infants. Biol Neonate 1971, 19(1):185-193.
104. Lorkin P.A. Fetal and embryonic haemoglobins. J Med Genet 1973 Mar, 10(1):50-64.
105. Miller S.T., Sleeper L.A., Pegelow C.H., Enos L.E., Wang W.C., Weiner S.J., et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med 2000 Jan 13, 342(2):83-89.