Document Type: Original Research
Regional Haemoglobinopathy Detection & Management Centre (RHDMC), Department of Pathology, IGGMCH, Nagpur City-Maharashtra State, India
Background: Until now, trimodal distribution of HbS has been seen by six different studies in the world when associated with alpha-thalassemia with confirmation by corresponding alpha-genotyping studies. The RBC indices reduce as alpha-globin genes reduce in sickle cell trait (SCT) patients, which decreases the extent of intra-vascular sickling and thus betters the clinical course of the patients. This is a pioneer study conducted on Central Indian poor population to use the already proven six studies to screen associated alpha-thalassemia in SCT patients thus, circumventing the much costlier alpha-genotyping studies. Moreover, it aimed to study the haematological parameters in such cases.
Methods: The study was performed at RHDMC, IGGMC, Nagpur, India from 2003 to 2012. The sample population was suspected cases of haemolytic anaemia. CBC and RBC indices were obtained by a cell analyzer. The sickle solubility test positively screened cases were confirmed by agar-gel haemoglobin electrophoresis at pH 8.6. Finally, quantitative assessment of haemoglobin variants was performed by HPLC.
Results: Out of total 5819 cases over ten years, 933 cases were sickle heterozygotes. Overall, 180/933 subjects were predicted to be homozygous alpha-thalassemia and 338/933 were heterozygous alpha-thalassemia, based on trimodal distribution of HbS.
Conclusion: Genotyping is costlier for majority of the poor non-affording patients in Indian government set-ups, so this study is suitable to screen for associated alpha-thalassemia in SCT patients.
- Higgs DR, Weatherall DJ. The alpha thalassaemias. Cell Mol Life Sci 2009; 66(7): 1154–62.
- Weatherall DJ. Hemoglobinopathies worldwide: present and future. Curr Mol Med 2008; 8(7): 592–9.
- Lukens JN. The thalassemias and related disorders: quantitative disorders of hemoglobin synthesis. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, editors. Wintrobe's clinical hematology. 10th ed. Egypt: Mass Publishing C; 1999. pp. 1405–48.
- Shaji RV, Eunice SE, Baidya S, Srivastava A, Chandy M. Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population. Br J Hematol 2003;123(5): 942–7.
- Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR, Colah RB, Kadam MD, et al. The effect of alpha-thalassemia on sickle-cell anemia linked to the Arab-Indian haplotype in India. Am J Hematol 1997; 55(2): 104–9.
- Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86(6): 480–7.
- López C, Saravia C, Gomez A, Hoebeke J, Patarroyo MA. Mechanisms of genetically-based resistance to malaria. Gene 2010; 467(1-2): 1-12.
- Aidoo M, Terlouw DJ, Kolczak MS, McElroy PD, ter Kuile FO, Kariuki S, et al. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet 2002; 359(9314): 1311–2.
- Steinberg MH, Embury SH. Alpha-Thalassemia in blacks: genetic and clinical aspects and interactions with the sickle cell haemoglobin gene. Blood 1986; 68(5): 985–90.
- De Ceulaer K, Higgs DR, Weatherall DJ, Hayes RJ, Serjeant BE, Serjeant GR.Alpha-Thalassemia reduces the hemolytic rate in homozygous sickle-cell disease. N Engl J Med 1983; 309(3):189–90.
- Brittenham G, Lozoff B, Harris JW, Sharma VS, Narasimhan S. Sickle cell anemia and trait in a population of southern India. Am J Hematol 1977; 2(1): 25-32.
- Brittenham G, Lozoff B, Harris JW, Mayson SM, Miller A, Huisman TH. Sickle cell anemia and trait in southern India: further studies. Am J Hematol 1979; 6(2): 107-23.
- Abraham EC, Huisman TH. Difference in affinity of variant beta chains for alpha chains: a possible explanation for the variation in the percentage of beta chain variants in heterozygotes. Hemoglobin 1977; 1(8): 861-73.
- Huisman TH. Trimodality in the percentage of beta chain variant in heterozygotes: the effect of the number of active Hb alpha structural loci. Haemoglobin 1977; 1(4): 349-82.
- Embury SH, Dozy AM. Correlation of α-globin phenotype with haematologic parameters in sickle cell trait. Blood 54: suppl. 1, p. 53 (1979).
- Wong WC, Ali MA, Boyadjian SE. Sickle Cell trait in Canada-Trimodal Distribution of Hb S as a result of Interaction withalpha thalassaemia gene. Acta Hematol 1981; 65(3):157-63.
- El-Hazmi MA. Studies on sickle cell heterozygotes in Saudi Arabia- Interaction with alphathalassaemia. Acta Haematol1986; 75(2): 100-4.