THE EFFECT OF ALPHA THALASSEMIA, HBF and HBC ON HAEMATOLOGICAL PARAMETERS OF SICKLE CELL DISEASE PATIENTS IN IBADAN, NIGERIA. ALPHA THALASSEMIA, HBF and HBC ON HAEMATOLOGICAL PARAMETERS OF SICKLE CELL DISEASE PATIENTS
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Keywords
Sickle cell, blood cell count, alpha thalassemia, Hemoglobin F, Hemoglobin C, genotype - phenotype association
Abstract
Background: Sickle cell disease is a protean disease with limited data on the phenotypic and genetic variants in Nigeria. This study was conducted to provide baseline data on these variants by characterizing the existing forms of sickle cell disease and correlating these with basic hematological parameters.
Methods: Adult and pediatric patients with SCD were recruited from a tertiary health centre in Nigeria. Patients were age and sex matched with healthy controls. Blood samples were obtained for Full Blood Count, phenotyping by High Performance Liquid Chromatography and genotyping for alpha thalassemia by multiplex gap polymerase chain reaction. Data analysis was done using IBM SPSS statistics version 23.
Results: A total of 130 patients with sickle cell disease and 117 controls were studied. Alpha thalassemia in the study population was due to a 3.7kb deletion in the alpha globin gene cluster at a prevalence of 45.4% in the patients and 47% in controls. The prevalence of the various existing forms of SCD genotype was: Homozygous S without alpha gene deletion (HbSS)- 39.2%; HbSC - 10.8%; HbSα+1- 35.4%; HbSα+2 - 6.9% and HbSF- 7.7%. HbA2 was significantly elevated in individuals with two alpha gene deletions (HbSα+2). HbF and HbA2 were negatively correlated with each other (r= -0.587, p < 0.001). Individuals with the HbSC genotype followed by HbSα+2 had the best hematological parameters.
Conclusions: Hematological parameters varied with hemoglobin genotype. The C hemoglobin and homozygous alpha thalassemia deletion had better ameliorating effect on SCD hematological parameters than the F hemoglobin in this population.
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References
2. Milner PF, Garbutt GJ, Nolan-Davis LV, Jonah F, Wilson LB, Wilson JT. Habara A, Steinberg MH. Minireview: Genetic basis of heterogeneity and severity in sickle cell disease. Exp Biol Med (Maywood). 2016;241(7):689-96.
3. Thein SL. Genetic modifiers of sickle cell disease. Hemoglobin. 2011; 35(5-6):589-606.
4. Falusi AG & Esan GF. Foetal haemoglobin levels in sickle cell anaemia in Nigerians Afr. J Med Med Sci 1989; 18: 145-149
5. Kotila TR, Fawole OI, Shokunbi WA Haemoglobin F and clinical severity of sickle cell anaemia among Nigerian adults Afr J Med Med Sci. 2000;29(3-4):229-31.
6. Murray N, Serjeant BE, Serjeant GR. Sickle cell-hereditary persistence of fetal haemoglobin and its differentiation from other sickle cell syndromes. Br J Haematol. 1988;69:89–92
7. Stevens MCG, Hayes RJ, Vaidya S. Serjeant GR: Fetal hemoglobins and clinical severity of homozygous sickle cell disease in early childhood. J Pediatr 1981; 98:37-41.
8. Adeyemo TA, Ojewunmi OO, Oyetunji IA, Rooks H, Rees DC, Akinsulie AO, et al. A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia. PLoS ONE 2018; 13(6): e0197927.
9. Falusi A.G., Esan G.J.F., Ayyuo H., Higgs D.R. Alpha- thalassaemia in Nigeria: Its interaction with Sickle Cell Disease. Eur J. Haematol 1987;38:370-375.
10. Ballas SK, Gay RN, Chehab FF. Is Hb A2 elevated in adults with sickle-alpha-thalassemia (beta(S)/beta(S); -alpha/-alpha)? Hemoglobin. 1997;21(5):405-450
11. Liu YT, Old JM, Miles K, Fischer CA, Weatherall DJ, Clegg JB. Rapid detection of alpha thalassemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. Br J Haematol 2000; 108(2):295-299.
12. Y. Daniel, “Haemoglobinopathy diagnostic tests: blood counts, sickle solubility test, haemoglobin electrophoresis and high-performance liquid chromatography,” in Practical Management of Haemoglobinopathies, I. E. Okpala, Ed., Blackwell Publishing, 2004; 10–19.
13. Inusa BP, Daniel Y, Lawson JO, Dada J, Matthews CE, et al. (2015) Sickle Cell Disease Screening in Northern Nigeria: The Co- Existence of Β- Thalassemia Inheritance. Pediat Therapeut 2015;5(3):3-6. doi:10.4172/2161-0665.1000262
14. Brown BJ, Akinkunmi BF, Fatunde OJ. Age at diagnosis of sickle cell disease in a developing country. African Journal of Medicine and Medical Sciences 2010; 39(3) :221-225.
15. Akinbami A, Uche E, Dosunmu A, Osikomaiya B, Adediran A, Sarah JO, Esther O, Badiru M, Bamiro R. Haemoglobin F and A2 profiles among sickle cell anaemia patients in Lagos State University Teaching Hospital (LASUTH), Nigeria. Ann Trop Pathol 2018;9:26-31
16. Adeyemo T, Ojewunmi O, Oyetunji A. Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria. Pan Afr Med J. 2014;18:71. doi: 10.11604/pamj.2014.18.71.4239.
17. Saraf SL, Molokie RE, Nouraie M, Sable CA, Luchtman-Jones L, Ensing GJ, Campbell AD, Rana SR, Niu XM, Machado RF, Gladwin MT, Gordeuk VR. Differences in the clinical and genotypic presentation of sicklecell disease around the world PaediatrRespir Rev. 2014; 15(1): 4–12. doi:10.1016/j.prrv.2013.11.003
18. Forget BG & Bunn HF. Classification of the Disorders of Hemoglobin. Cold Spring Harb Perspect Med. 2013; 3(2): a011684
19. Steinberg MH & Embury SH. Alpha-thalassemia in Blacks: Genetic and Clinical Aspects and Interactions with the Sickle Hemoglobin Gene Blood, 1986; 68(5): 985-990.
20. Higgs DR, Pressley L, Clegg JB, Weatherall DJ, Serjeant G.R. α Thalassaemia in Black Populations Johns Hopkins Med. J. 1980: 146:300-10
21. Altay C, Gravely ME, Joseph BR, Williams DF. Alpha thalassemia-2 and the variability of hematological values in children with sickle cell anemia. Pediatr Res I 1981;5: 1093
22. Embury SH, Dozy AM, Miller J, Davis JR, Kleman KM, Preisler H, Vichinsky E, Lande WN, Lubin BH, Kan YW, Mentzer WC. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med. 1982;306:270–274
23. Steinberg MH and Sebastiani P. Genetic Modifiers of Sickle Cell Disease. Am J Hematol. 2012; 87(8): 795–803
24. Rumaney MB, Ngo Bitoungui VJ, Vorster AA, Ramesar R, Kengne AP, Ngogang J, Wonkam A. The Co-inheritance of alpha-thalassemia and sickle cell anemia is associated with better hematological indices and lower consultations rate in Cameroonian patients and could improve their survival. PLoS One. 2014; 9(6):e100516).
25. Steinberg MH, Chui DH, Dover GJ, Sebastiani P, Alsultan A. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014;123(4):481-485. doi: 10.1182/blood-2013-09-528067.
26. Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, Chui DHK, Steinberg MH. Fetal hemoglobin in sickle cell anemia. Blood. 2011; 118(1): 19–27. doi: 10.1182/blood-2011-03-32525
27. Estepp JH, Smeltzer MP, Kang G, Li C, Wang WC, Abrams C, Aygun B, Ware RE, Nottage K, Hankins JS. A Clinically Meaningful Fetal Hemoglobin Threshold for Children with Sickle Cell Anemia During Hydroxyurea Therapy. Am J Hematol. 2017; 92(12): 1333–1339
28. Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: A simple parameter with multiple clinical applications, Critical Reviews in Clinical Laboratory Sciences, 2015;52(2): 86-105, DOI: 10.3109/10408363.2014.992064
29. Serjeant G.R. The natural history of sickle cell disease. Cold Spring Harb Perspect Med. 2013; 3(10):a011783
30. Milner PF, Garbutt GJ, Nolan-Davis LV, Jonah F, Wilson LB, Wilson JT.The effect of Hb F and alpha-thalassemia on the red cell indices in sickle cell anemia. Am J Hematol. 1986;21(4):383-395
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