Erythrocyte Indices MCV and/or MCH as First Round Screening Followed by Hb-analysis for β-thalassemia Carrier State
Abstract
BACKGROUND: Being located in the global thalassemia belt area, Indonesia is estimated harboring about 10% thalassemia carriers; however, screening program is still diversely scattered across the country. Numerous erythrocyte indices have been introduced to help identifying thalassemia carriers with contradictory results. Therefore, this study had compared the use of mean corpuscular volume (MCV) and/or mean corpuscular hemoglobin (MCH) values and the most erythrocyte indices used in Indonesia which were Mentzer Index (MI) and Shine & Lal Index (SLI), as a first attempt in a mass screening for β-thalassemia carrier.
METHODS: This was a retrospective study, evaluating laboratory data from family members of thalassemia major subjects. The sensitivity and specificity of MI and SLI were calculated. HbA2 >3.5% was used as a golden standard for β-thalassemia carrier and DNA examination was conducted to confirm β-globin mutation.
RESULTS: Out of 160, 28.8% of the subjects had low Hb concentration. Interestingly, 79.4% of the subjects had low MCV and/or MCH with or without low Hb concentration. In this study, specificity and sensitivity of MI were 82.2% and 83.8%, whereas of SLI were 96% and 40.5%, respectively. Low MCV and/or MCH had covered IVS1nt5 and Cd26 mutation at β-globin gene; whereas MI and SLI had missed some samples, leading to false negative of thalassemia carrier results, when using MI or SLI only.
CONCLUSION: MCV<80 fl and/or MCH<27 pg is the best first round mass screening method for β-thalassemia carrier in a limited facility area. However, Hb electrophoresis should be gradually installed regionally in various places wherever possible, as well as DNA analysis to confirm the mutation for an optimal carrier diagnosis.
KEYWORDS: HbA2, HbE, iron deficiency anemia, Mentzer Index, Shine and Lal Index
Full Text:
PDFReferences
Fucharoen S, Winichagoon P. Haemoglobinopathies in Southeast Asia. Indian J Med Res. 2011; 134(4): 498-506, PMID.
Siregar OR, Siregar RS, Lubis B. Renal function in children with β-thalassemia major treated with iron chelating agent. Indones Biomed J. 2020; 12(3): 214-9, CrossRef.
Kementerian Kesehatan Republik Indonesia: Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular. Pedoman Pengendalian Penyakit Thalassemia di Fasilitas Kesehatan Tingkat Pertama. Jakarta: Kementerian Kesehatan Republik Indonesia; 2017.
Handayani NSN, Husna N, Rahmil G, Ghifari RA, Widyawati L, Lesmana I. Splice-site and frameshift mutations of β-globin gene found in thalassemia carrier screening in Yogyakarta Special Region, Indonesia. Indones Biomed J. 2021; 13(1): 55-60, CrossRef.
Candrarukmi D, Moelyo AG, Riza M. Glycated albumin as marker for early hyperglycemia detection in adolescent with β thalassemia major. Indones Biomed J. 2021; 13(3): 281-8, CrossRef.
Vehapoglu A, Ozgurhan G, Demir AD, Uzuner S, Nursoy MA, Turkmen S, Kacan A. Hematological indices for differential diagnosis of Beta thalassemia trait and iron deficiency anemia. Anemia. 2014; 2014: 576738, CrossRef.
Kementrian Kesehatan Republik Indonesia. Riset Kesehatan Dasar 2013. Jakarta: Kementrian Kesehatan Republik Indonesia; 2013, article.
Nurdianto AR, Arwati H, Dachlan YP, Febiyanti DA. The relationship of hemoglobin, interleukin-10 and tumor necrosis factor alpha levels in asymptomatic malaria patients in Trenggalek, Jawa Timur, Indonesia. Mol Cell Biomed Sci. 2019; 3(1): 13-6, CrossRef.
Hoffmann JJ, Urrechaga E, Aguirre U. Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia: a meta-analysis. Clin Chem Lab Med. 2015; 53(12): 1883-94, CrossRef.
Plengsuree S, Punyamung M, Yanola J, Nanta S, Jaiping K, Maneewong K, et al. Red cell indices and formulas used in differentiation of β-thalassemia trait from iron deficiency in Thai adults. Hemoglobin. 2015; 39(4): 235-9, CrossRef.
Harahap RIM, Prihatni D, Rostini T. The compatibility measurement of Mentzer, England & Faser, Shine & Lal, and Srivastava indices to the haemoglobin electrophoresis result for beta thalassemia trait screening. Bali Med J 2019; 8(2): 311-5, CrossRef.
Kumar A, Saha D, Kini J, Murali N, Chakraborti S, Adiga D. The role of discriminant functions in screening beta thalassemia trait and iron deficiency anemia among laboratory samples. J Lab Physicians. 2017; 9(3): 195-201, CrossRef.
Jamnok J, Sanchaisuriya K, Chaitriphop C, Sanchaisuriya P, Fucharoen G, Fucharoen S. A new indicator derived from reticulocyte hemoglobin content for screening iron deficiency in an area prevalent for thalassemia. Lab Med. 2020; 51(5): 498-506, CrossRef.
Agouti I, Merono F, Bonello-Palot N, Badens C. Analytical evaluation of the Capillarys 2 flex piercing for routine haemoglobinopathies diagnosis. Int J Lab Hematol. 2013; 35(2): 217-21, CrossRef.
Maskoen AM, Reniarti L, Sahiratmadja E, Sisca J, Effendi SH. Shine & Lal index as a predictor for early detection of β-thalassemia carriers in a limited resource area in Bandung, Indonesia. BMC Med Genet. 2019; 20(1): 136, CrossRef.
World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity: WHO/NMH/NHD/MNM/11.1. Geneva: World Health Organization; 2011, article.
Schoorl M, Schoorl M, van Pelt J, Bartels PC. Application of innovative hemocytometric parameters and algorithms for improvement of microcytic anemia discrimination. Hematol Rep. 2015; 7(2): 5843, CrossRef.
Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med. 2013; 3(2): a011775, CrossRef.
Chatterjee T, Chakravarty A, Chakravarty S. Population screening and prevention strategies for thalassemias and other hemoglobinopathies of Eastern India: experience of 18,166 cases. Hemoglobin. 2015; 39(6): 384-8, CrossRef.
Urrechaga E, Hoffmann JJML. Critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with microcytic anemia. Clin Chem Lab Med. 2017; 55(10): 1582-91, CrossRef.
Surjawan Y, Tan HL, Setiabudy RD, Rositawati W. Early screening of hemoglobinopathy in Indonesia using erythrocyte indices. Indones Biomed J. 2017; 9(2): 99-105, CrossRef.
Sanchaisuriya K, Fucharoen S, Fucharoen G, Ratanasiri T, Sanchaisuriya P, Changtrakul Y, et al. A reliable screening protocol for thalassemia and hemoglobinopathies in pregnancy: an alternative approach to electronic blood cell counting. Am J Clin Pathol. 2005; 123(1): 113-8, CrossRef.
Verhovsek M, So CC, O'Shea T, Gibney GT, Ma ES, Steinberg MH, et al. Is HbA2 level a reliable diagnostic measurement for β-thalassemia trait in people with iron deficiency? Am J Hematol. 2012; 87(1): 114-6, CrossRef.
Sahiratmadja E, Seu MMV, Nainggolan IM, Mose JC, Panigoro R. Challenges in thalassemia carrier detection in a low resource setting area of Eastern Indonesia: the use of erythrocyte indices. Mediterr J Hematol Infect Dis. 2021; 13(1): e2021003, CrossRef.
Li J, Xie XM, Liao C, Li DZ. Co-inheritance of α-thalassaemia and β-thalassaemia in a prenatal screening population in mainland China. J Med Screen. 2014; 21(4): 167-71, CrossRef.
Amato A, Cappabianca MP, Lerone M, Colosimo A, Grisanti P, Ponzini D, et al. Carrier screening for inherited haemoglobin disorders among secondary school students and young adults in Latium, Italy. J Community Genet. 2014; 5(3): 265-8, CrossRef.
Ahmadnezhad E, Sepehrvand N, Jahani FF, Hatami S, Kargar C, Mirmohammadkhani M, et al. Evaluation and cost analysis of national health policy of thalassaemia screening in West-Azerbaijan province of Iran. Int J Prev Med. 2012; 3(10): 687-92, PMID.
Koren A, Profeta L, Zalman L, Palmor H, Levin C, Zamir RB, et al. Prevention of beta thalassemia in Northern Israel - a cost-benefit analysis. Mediterr J Hematol Infect Dis. 2014; 6(1): e2014012, CrossRef.
Ansari SH, Baig N, Shamsi TS, Saif-ur-Rehman, Ansari ZH, Behar Z, et al. Screening immediate family members for carrier identification and counseling: a cost-effective and practical approach. J Pak Med Assoc. 2012; 62(12): 1314-7, PMID.
Sahiratmadja E, Maskoen AM, Effendy DSH, Panigoro R. Exploring the willingness for carrier screening among extended family members of a thalassemia carrier individual: a lesson learned. J of Biomed & Clin Sci. 2017; 2(2): 8-10, article.
Roth IL, Lachover B, Koren G, Levin C, Zalman L, Koren A. Detection of β-thalassemia carriers by red cell parameters obtained from automatic counters using mathematical formulas. Mediterr J Hematol Infect Dis. 2018; 10(1): e2018008, CrossRef.
Wild BJ, Chohan DK, Harteveld CL, De la Salle B. Further evaluation of the world health organization international reference reagent for Haemoglobin A2 measurement. Int J Lab Hematol. 2021; 43(3): 494-9, CrossRef.
DOI: https://doi.org/10.18585/inabj.v14i3.1960
Copyright (c) 2022 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
