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Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study

Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta... Background: Screening of β thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of β thalassemia carriers and iron deficiency anemia among relatives of β thalassemia patients in Mid Delta, Egypt. Methods: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with β thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. Results: The total prevalence of iron deficiency anemia among close relatives of confirmed β thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al- Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al- Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). β thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). Conclusion: More than one-third of relatives of patients with β thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with β thalassemia in Egypt. Keywords: Screening, Thalassemia carriers, Mid Delta, Egypt * Correspondence: elshanshory@gmail.com; Mohamed.elshanshoury@med.tanta.edu.eg Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 2 of 8 1 Introduction law, brothers and sisters are considered second degree Thalassemia is an autosomal recessive common genetic relatives. Grandparents, grandchildren, aunts, uncles, disorder throughout the world [1]. Almost 70,000 infants nieces, and nephews are considered third degree rela- are born with β thalassemia worldwide each year [2]. tives, and cousins are considered fourth degree relatives. Consanguineous marriages, a high fertility rate, a high The study population included 963 male and 1155 fe- birth rate, a low educational level, and early marriages, male. The excluded relatives were those with other combined with an unawareness of the thalassemia prob- hemolytic anemia, relatives of known α thalassemic pa- lem, make developing countries to have a high number tients, and parents of β thalassemic patients. of transfusion-dependent thalassemia children in the world [3]. In general, patients with thalassemia major 2.3 Data collection place a considerable burden on their families and health All the individuals included in the study were subjected authorities [4]. to full history taking, thorough clinical examination, and Several countries have implemented national preven- the following investigations: complete blood count tion programs, including public awareness and educa- (CBC) by automated ABX PENTRA XL80 device. The tion, carrier screening and counseling, and information cut-off level for hemoglobin used to classify subjects into on the prenatal and pre-implantation diagnosis of the anemic and non-anemic; the hemoglobin level less than disease [5]. Carrier screening has had great success, lead- 11 g/dl in the age group between 6 and 12 years [11], ing to a decline in the birth rate of thalassemia major in and hemoglobin level < 13g/dl in male and < 12 g/dl in some countries [5]. It has been estimated that one thou- female in the age group more than 12 years [12]. Mean sand children out of 1.5 million live births are born each corpuscular volume (MCV) of less than 80 fl and/or year suffering from thalassemia in Egypt [6]. It is re- mean corpuscular hemoglobin (MCH) of less than 27 pg ported that the carrier rate in Egypt is between 9 to 10% are generally used as cut-off points for further screening of the population [7]. with serum ferritin to exclude iron deficiency anemia. In Egypt, despite the high prevalence of β thalassemia Serum ferritin less than 15 ng/ml is considered diagnos- carriers and the growing number of patients born each tic of iron deficiency [13]. Blood samples of participants year, there is no national thalassemia prevention pro- with normal serum ferritin were analyzed by high per- gram [8]. Few studies were performed to assess the car- formance liquid chromatography (HPLC) for quantita- rier rate of β thalassemia [9, 10]. Selective screening tive estimation of an elevated HbA2 level, using the approach within the families suffering from thalassemia hemoglobin analyzer ARKRAY ADAMS A1C HA-8180T is ideal and more feasible in highly prevalent regions (Japan) device. HbA2 < 3.5% is considered diagnostic of with limited resources. The aim of our study was to de- β thalassemia carrier state [14]. termine β thalassemia carriers, in addition to iron defi- ciency anemia, individuals among relatives of β 2.3.1 Sample collection and storage thalassemia patients, especially in population crowded Five milliliters of whole blood were collected from every regions, for raising the awareness of the problem among subject into three vacutainer tubes. The first tube con- this high-risk population. taining EDTA was used as an anticoagulant for a complete blood picture (CBC) and 2 mm into a second 2 Methods tube for high performance liquid chromatography 2.1 Study design and setting (HPLC). The third tube was used for serum ferritin The current study is a cross-sectional multi-center study measurement for participants with hypochromic micro- conducted on 2118 relatives of patients with β thalas- cytic anemia. semia from different Egyptian governorates in the Mid Delta region (Al-Gharbia, Al-Dakahlia, Al-Menuofiea, Al-Sharkhia, Kafer el-Sheikh, Al-Beheira, and 2.4 Statistical analysis of data Alexandria). The collected data were coded, verified for complete- ness, recorded in a Microsoft Excel master sheet, and 2.2 Participants then statistically analyzed utilizing the SPSS™ (Statistics The study participants represented respondents who Program for Social Studies) software version 25 pro- were eligible and agreed to participate in the study from duced by IBM, Chicago, IL, USA. Means and standard the relatives (2nd, 3rd, and 4th degree) of all known β deviations were used to describe numerical values, while thalassemic children attending hematology/oncology frequencies were used for categorical ones. clinics at Tanta, Zagazig, Mansoura, Menuofia, and The Chi-square test was used to test the differences Alexandria Universities’ Hospitals during the 48 months between categorical variables, while the Mann-Whitney of the study (from 2016-2020). According to Egyptian U test was used for independent quantitative variables. P El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 3 of 8 value was considered significant at < 0.05 and < 0.001 total number of participants in this study was 2118 chil- for highly significant results. dren. Males constituted 936 participants (45.47%) while 54.53% (1155) were females. Participants with hypochro- 3 Results mic microcytic anemia constituted 1123 (53.02%). Figure 1 shows the screening algorism among the close Table 1 illustrates the prevalence of iron deficiency relatives of patients with confirmed β thalassemia. The anemia and β thalassemia carriers among the study Fig. 1 Screening algorithm for the participants El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 4 of 8 Table 1 Prevalence of iron deficiency anemia and β thalassemia carriers among studied relatives in Mid Nile Delta Egyptian Governorates (2016-2020) Governorate Total examined Iron deficiency anemia β thalassemia carrier (Group 1) (Group 2) NN % N % Al-Gharbia 182 82 45.05 56 30.77 Al-Menoufia 300 65 21.67 75 25.00 Al-Sharkia 265 13 4.91 136 51.32 Al-Dakahilia 668 100 14.97 248 37.13 Al-Beihera 219 22 10.05 70 31.96 Alexandria 326 69 21.17 108 33.13 Kafr-Elsheikh 158 13 8.23 66 41.78 Total 2118 364 17.19 759 35.84 χ 154.32 50.36 ** P < 0.001 0.001** **Highly significant (P < 0.01) participants in relation to the governorate of residence. The Table 3 shows the comparison of serum ferritin and totalprevalenceofirondeficiencyanemiaamong closerela- HbA2% between relatives who are β thalassemia carriers tives of confirmed β thalassemia patients in the Nile Delta and those with iron deficiency anemia. Serum ferritin region was found to be 17.19%. The highest prevalence of shows a significantly lower mean of 8.20 ± 3.78 ng/ml iron deficiency anemia (45.05%) was reported in Al- among group 1 than 68.73 ± 49.33 ng/ml among group Gharbia Governorate, followed by Al-Menoufia Governor- 2(p = 0.001). In comparison, the group’s 2 hemoglobin ate (21.67%) and the lowest prevalence was that of Al- A2% was significantly higher (4.55 ± 0.5) % compared to Sharkia Governorates (4.91%), these differences were highly the mean of 2.54 ± 0.49% detected among group 2 (p < statistically significant (p < 0.001). On the other hand, the 0.001). total carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia 4 Discussion Governorates (51.32%), followed by Kafr-Alsheikh Gover- Symptomatic β thalassemia syndromes constitute a sig- norate (41.78%), and Al-Dakahilia (37.13%). Al-Menoufia nificant public health problem in Egypt; the high preva- Governorate had the lowest prevalencerate(25.00%). These lence of beta thalassemia carriers, combined with a differences were also found highly statistically significant (p growing number of newly born cases, underscores the < 0.001). critical significance of developing a beta thalassemia pre- Table 2 demonstrates a comparison of blood indices vention program in Egypt [15]. Prevention by carrier de- between β thalassemia carriers and iron deficiency tection is needed in populations with a high incidence of anemia of the studied relatives. Only hemoglobin con- the disease, such as Egypt. Improving public awareness centration showed no significant difference between the and mandatory premarital screening for carrier detection two groups (p = 0.152). The total number of red blood 6 3 are essential to offer prenatal diagnosis and genetic corpuscles among group 2 (5.28 ± 0.63) × 10 /mm was counseling for high-risk couples [15]. significantly higher than that recorded for children with 6 3 Various approaches of carrier screening programs the group 1 (3.74 ± 0.56) × 10 /mm (p = 0.001). The were conducted in several countries. They include gen- mean hematocrit percentage in group 2 (33.31 ± 4.09) % eral population screening, high-risk group screening, was significantly higher than that of group 1 (32.7 ± antenatal screening, and cascade screening or extended 3.71) (p = 0.001). Besides, mean corpuscular volume was family screening [16]. As an autosomal recessive disease, significantly higher among group 1 (67.83 ± 7.21) fl together with the high rate of consanguineous marriages compared to group 2 (62.42 ± 6.37) fl (p = 0.001). The in our country, the expected highest prevalence of β same applies for MCH, 22.70 ± 2.81 versus 20.32 ± 2.21 thalassemia carriers will be among the patient’s relatives pg (p = 0.001); MCHC, 33.94 ± 2.32 g/dl versus 32.83 ± who are a good target for screening. This type of screen- 2.31 g/dl (p = 0.001). ing may offer an alternative to population screening for Lastly, group 1 had a significantly higher mean red cell identifying present and future couples at risk for produ- distribution width, 16.89 ± 2.28%, compared to 15.30 ± cing affected children [17]. 2.18% for group 2 (p = 0.001). El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 5 of 8 Table 2 Complete blood count of β thalassemia carriers and iron deficiency anemia participants in Mid Nile Delta Egyptian Governorates (2016-2020) Variable Iron deficiency anemia β thalassemia carrier MW P (Group 1) (Group 2) 6 3 Red blood corpuscles (X10 /mm ) Mean ± SD 3.74 ± 0.56 5.28 ± 0.63 13.45 0.001** Range 2.30-4.96 4.00-6.60 Median 3.80 5.28 Hemoglobin (g/dl) Mean ± SD 10.60 ± 1.21 10.95 ± 1.20 1.43 0.152 Range 6.60-12.90 9-15.40 Median 10.80 10.90 Hematocrit value (%) Mean ± SD 32.7 ± 3.71 33.31 ± 4.09 2.34 0.019** Range 18.50-39.7 20.20-44.90 Median 32.70 33. 10 Mean corpuscular volume (fl) Mean ± SD 67.83 ± 7.21 62.42 ± 6.37 7.70 0.001** Range 45-79 45.0-79.0 Median 69.00 62.00 Mean corpuscular hemoglobin (pg) Mean ± SD 22.70 ± 2.81 20.32 ± 2.21 7.20 0.001** Range 14.60-27 15.20-27.20 Median 22.75 20.10 Mean corpuscular hemoglobin concentration (g/dl) Mean ± SD 33.94 ± 2.32 32.83 ± 2.31 3.95 0.001** Range 29.50-38.20 26.80-37.80 Median 34.00 32.30 Red cell distribution width (%) Mean ± SD 16.89 ± 2.28 15.30 ± 2.18 5.93 0.001** Range 11.90-21.30 11.00-18.40 Median 17.4 16.00 SD standard deviation MW: Z value of Mann-Whitney U test **Highly significant (P < 0.01) The current study involved 2118 relatives of patients (67.59%), with a prevalence rate of 35.84% among the with β thalassemia from different Egyptian governorates studied relatives of the patients. This is about 3-4 times in the Mid Delta region. Microcytic hypochromic higher than the estimated carrier rate of 9-10% in the anemia was diagnosed in 53.02% of the studied groups. general population [7]. This result supports what was Carrier detection in this study was based upon the pres- previously reported that β thalassemia carriers are more ence of microcytic hypochromic anemia, normal serum prevalent in siblings of thalassemia major than the nor- ferritin level together with HbA2 level of < 3.5% [14]. mal population [18]. Most of the previous studies in- β thalassemia carrier state constituted the majority cluded general population and pregnant women among children with microcytic hypochromic anemia screening, with few that included relatives of thalassemia Table 3 Serum ferritin and HbA2 of β thalassemia carriers and iron deficiency anemia participants Mid Nile Delta Egyptian Governorates (2016-2020) Variable Iron deficiency anemia β- thalassemia carrier MW P (Group 1) (Group 2) ** Serum ferritin (ng/ml) Mean ± SD 8.20 ± 3.78 68.73 ± 49.33 23.35 0.001 Range 1.00-14.90 15.50-349 Median 6.85 55.00 ** Hemoglobin A2% Mean ± SD 2.54 ± 0.49 4.50 ± 0.59 23.36 0.001 Range 1.30-3.40 3.60-6.99 Median 2.60 4.500 SD standard deviation MW: Z value of Mann-Whitney U test **Highly significant (P < 0.01) El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 6 of 8 patients. To our knowledge, there is no published data below 15 ng/ml. In the present study, IDA was diag- about similar studies in Egypt. nosed in 17.19% of the participants. Though lower than Our estimated prevalence of β thalassemia trait (βTT) what was estimated in the general population, IDA is in relatives of patients is nearly similar to what was re- prevalent among relatives of thalassemia patients and ported in Rawalpind, Pakistan (31%) by Ahmed et al. should be searched for and adequately treated. The high- [19] while it is higher than the prevalence reported by est prevalence of IDA (45.05%) was reported in Al- Gorakshakar and Colah (21.9%) in extended family Gharbia Governorate, followed by Al-Menoufia Gover- screening in India [17]. On the other hand, it is lower norate (21.67%), and the lowest prevalence was that of than what was found in other studies done in Faisalabad Al-Sharkia Governorates (4.91%). The significant differ- (44.4%) [20], Kota (48.76%) [18], Bandung (59.6%) [21], ence between different governorates could be related to Karachi (62.2%) [22], Bhopal (76%) [23], and North India the involvement of rural areas in governorates with a (76.92%) [24]. This discrepancy could be explained by high prevalence of IDA, lower-income families with lim- the differences in general prevalence rate in the geo- ited access to iron-rich foods, and inefficient utilization graphic areas involved, selection criteria in each study of available micronutrients as a result of infectious dis- (siblings only or extended family, the number of in- eases, particularly helminthic infections [28]. cluded individuals), and genetic heterogeneity of thalas- Comparing the hematological parameters of relatives semia gene. with βTT and those with IDA, no significant difference In this study, the highest carrier prevalence rate was was found regarding Hb level. In contrast, βTT relatives detected in Al-Sharkia Governorates and followed by had a significantly higher RBCs count, with significant Kafr-Alsheikh Governorate, Al-Dakahilia, while Al- lower MCV, MCH, MCHC, and RDW than IDA. Red Menoufia Governorate had the lowest prevalence rate. blood cell (RBC) count is known to be increased in both This variation between localities might be related to the thalassemia patients and carriers. It is considered a use- different rate of consanguineous marriage in different ful diagnostic adjunct because thalassemia has micro- Egyptian communities. In societies where the majority of cytic anemia, increasing the RBCs number. In contrast, couples are unrelated, genes for recessive disorders usu- other causes of microcytic anemias, including iron defi- ally run in families for many generations without mani- ciency anemia and anemia of chronic disease, are typic- festing through the birth of an affected child. By ally associated with a proportional decrease in the RBC contrast, gene variants are trapped within extended fam- number [29]. ily members [19]. Thus, in communities where consan- In accordance with our results, a high RBC count guinity is evident, one can identify even more carriers among BTT was reported by Demir et al. [30], Vehapo- [16]. It was reported that the cascade screening result glu et al. [27], and Jameel et al. [31]. Demir et al. [30] re- was more impressive in a small location. ported that RBC count is one of the most reliable For example, in Sardinia, by analyzing 11% of the discrimination indices in differentiation between βTT population, more than 90% of the “at risk” couples were and IDA, with 90% of the patients were correctly identi- detected [25]. An affected child is a predictor of high fied with RBC count. The majority of β thalassaemia car- genetic risk, and an extended family study may discover riers have reduced MCV and MCH levels in the several carriers and couples at risk before marriage or standard complete blood examination (FBE) [31]. Low reproduction [17]. Family studies provide a highly effect- MCV is the key indicator for diagnosis and screening for ive risk detection approach. Population screening is less thalassemia. It was suggested that an MCV of < 72 is effective, but carrier follow-up will detect elevated risk maximally sensitive and specific for the presumptive prior to any affected child’s birth. Moreover, the perfect diagnosis of thalassemia [32]. approach is to provide both family studies and premari- The red cell distribution width (RDW) index reflects tal or antenatal screening for the relatives of affected the heterogeneity in the size distribution of erythrocytes, children [19]. measuring the coefficient of variation around MCV [33]. Worldwide, beta thalassemia trait (βTT) and iron defi- It was found to be the most reliable index evaluated for ciency anemia (IDA) are the two most frequent causes discrimination between βTT and IDA, with 100% sensi- of microcytic anemia [26]. The differentiation between tivity and 92.6% specificity. This index can be used to ef- IDA and βTT is of prime importance, especially in these ficiently screen patients with microcytosis for further high-risk groups for being βT carriers [27]. Iron defi- hematologic studies to confirm β thalassemia [34]. ciency anemia is of high prevalence among Egyptian Normal RDW among βTT was also reported by other children. In the study performed by El-Beshlawy et al. studies [18, 35, 36]. So, microcytosis accompanied by a [9], about one-third of the studied population in upper high RBC count and normal RDW is highly suggestive & lower Egypt had IDA based on the presence of micro- of BTT [36]. A definitive differential diagnosis between cytic hypochromic anemia with serum ferritin level βTT and IDA is based on HbA2 electrophoresis, serum El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 7 of 8 iron, and ferritin levels [37]. In this regard, relatives of Haidy M Ibrahim; Dalia M Abd Elwahab; Reham F El- Moghazy; Lamia M Morad; Sara S Allam; Osama M Hussien) who share in the data collection. thalassemia patients with βTT have a significantly higher Lastly, we would like to thank, the Science, Technology, and Development level of HbA2 with significantly higher serum ferritin Fund (STDF) for the support and establishment of the Delta Thalassemia levels than those diagnosed as IDA. HbA2 levels (> Center: Control and Prevention. 3.5%) are the most significant parameter for identifying Authors’ contributions beta thalassemia carriers [28]. In this study, those with This research was carried out in collaboration with all authors. βTT have HbA2 ranged between 3.60-6.99% with a Conceptualization: ME, LS, SY, SR, AM, HH, SA, AA, AD, and SE. Methodology: AH, MW, ZM, MG, AA, MS, FE, RE, IK, and SS. Formal analysis and mean value of 4.55 ± 0.59%. In similar studies, the mean investigation: ME, LS, SY SR, AH, AA, MS, and IK. Writing—original draft HbA2% levels were 11.93 ± 0.5% [21], 4.99 ± 0.64% [16], preparation: SY SR, AH; YA, and SS. Writing— revision and editing: ME, LS, and 5.24 ± 1.14% [18]. and SS. All authors read and approved the final manuscript. Funding 4.1 Limitations of the study This work was supported by the Science, Technology, and Development An important limitation is the unavailability of molecu- Fund (STDF) [Capacity building Grant Project number 12439]. lar diagnosis of thalassemia and genetic screening to de- termine the genetic profile for individuals to identify Availability of data and materials The research data is available upon a reasonable request to the carriers. Besides, carrier identification by premarital and/ corresponding author. or early antenatal thalassemia screening is not mandatory and is not commonly used in Egypt. As the Declarations current state of thalassemia reflects the increasing need Ethics approval and consent to participate for national preventive program to reduce morbidity and The experimental protocol for involving humans was following the national/ mortality associated with this disease, particularly given international/institutional boards and the Declaration of Helsinki. The Ethics the country’s limited resources and that thalassemia pre- Committee of the Faculty of Medicine, Tanta University approved the study, with a reference code number (3031/01/15). A written informed consent was vention is cost-effective. We recommend initiating a na- taken from each study participant. Confidentiality of participants’ information tional program for extended family screening of relatives was guaranteed. with beta thalassemia patients as a preparatory and Consent for publication promising step to establish a national prevention pro- Not applicable. gram utilizing the data collected from the screening. Competing interests 5 Conclusion The authors declare no competing interests. Thalassemia carriers have characteristic hematological Author details parameters with mild anemia with microcytic hypochro- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, mic RBCs, increased red cell counts and normal RDW Egypt. Pediatric Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Pediatric Department, Faculty of Medicine, Alexandria that could help screening and together with HbA2 quan- University, Alexandria, Egypt. Pediatric Department, Faculty of Medicine, tification by Hb electrophoresis or HPLC, βTT can be Menoufia University, Shibin el Kom, Egypt. Pediatric Department, Faculty of easily diagnosed and screened for in high-risk groups Medicine, Mansoura University, Mansoura, Egypt. Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Clinical like family members and relatives of thalassemia pa- Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, tients. Family screening program by screening for micro- Egypt. Clinical and Chemical Pathology Department, Faculty of Medicine, cytic hypochromic anemia with increased RBCs reduced Alexandria University, Alexandria, Egypt. Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shibin el Kom, Egypt. Clinical MCV; MCH and normal RDW is a valuable and feasible Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, alternative to the population screening for detecting Egypt. Consultant of Biochemistry, Genetic Unit, Children Hospital, family members at risk of carrier state of βTT. Those Mansoura University, Mansoura, Egypt. Public Health and Community Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt. can be further identified by measuring HbA2. Received: 31 October 2020 Accepted: 16 August 2021 Abbreviations BTT: β thalassemia trait; CBC: Complete blood count; EDTA: Ethylenediaminetetraacetic acid; FBE: Full blood examination; Hb: Hemoglobin; HPLC: High performance liquid chromatography; IDA: Iron References deficiency anemia; MCH: Mean corpuscular hemoglobin; MCHC: Mean 1. Weatherall DJ, Clegg JB. 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Prevention of β-thalassemia in a large Pakistani family through cascade testing. Comm Genet. 2008;11(1):68–70. https://doi.org/10.1159/000111641. 21. 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. https://doi.org/10.1186/s12881-019-0868-x. 22. Ansari SH, Shamsi TS, Baig N, Ansari ZH, Perveen K, Erum S, 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. 23. Mishra AK, Tiwari A. Screening and molecular characterization of β- thalassaemia mutations in parents and siblings of thalassaemia major patients. Int J Biomed Res. 2014;3(2):481–6. https://doi.org/10.7439/ijbr.v5i2.4 24. Piplani S, Manan R, Lalit M, Manjari M, Bhasin T, Bawa J. NESTROFT - a valuable, cost effective screening test for beta thalassemia trait in north Indian Punjabi population. J Clin Diagn Res. 2013;7(12):2784–7. https://doi. org/10.7860/JCDR/2013/6834.3759. 25. Cao A, Galanello R. Effect of consanguinity on screening for thalassemia. N Engl J Med. 2002;347(15):1200–2. 26. Rahim F, Keikhaei B. Better differential diagnosis of iron deficiency anemia from beta-thalassemia trait. Turkish J Hematol. 2009;26(3):138–45. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the Egyptian Public Health Association Springer Journals

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Abstract

Background: Screening of β thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of β thalassemia carriers and iron deficiency anemia among relatives of β thalassemia patients in Mid Delta, Egypt. Methods: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with β thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. Results: The total prevalence of iron deficiency anemia among close relatives of confirmed β thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al- Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al- Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). β thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). Conclusion: More than one-third of relatives of patients with β thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with β thalassemia in Egypt. Keywords: Screening, Thalassemia carriers, Mid Delta, Egypt * Correspondence: elshanshory@gmail.com; Mohamed.elshanshoury@med.tanta.edu.eg Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 2 of 8 1 Introduction law, brothers and sisters are considered second degree Thalassemia is an autosomal recessive common genetic relatives. Grandparents, grandchildren, aunts, uncles, disorder throughout the world [1]. Almost 70,000 infants nieces, and nephews are considered third degree rela- are born with β thalassemia worldwide each year [2]. tives, and cousins are considered fourth degree relatives. Consanguineous marriages, a high fertility rate, a high The study population included 963 male and 1155 fe- birth rate, a low educational level, and early marriages, male. The excluded relatives were those with other combined with an unawareness of the thalassemia prob- hemolytic anemia, relatives of known α thalassemic pa- lem, make developing countries to have a high number tients, and parents of β thalassemic patients. of transfusion-dependent thalassemia children in the world [3]. In general, patients with thalassemia major 2.3 Data collection place a considerable burden on their families and health All the individuals included in the study were subjected authorities [4]. to full history taking, thorough clinical examination, and Several countries have implemented national preven- the following investigations: complete blood count tion programs, including public awareness and educa- (CBC) by automated ABX PENTRA XL80 device. The tion, carrier screening and counseling, and information cut-off level for hemoglobin used to classify subjects into on the prenatal and pre-implantation diagnosis of the anemic and non-anemic; the hemoglobin level less than disease [5]. Carrier screening has had great success, lead- 11 g/dl in the age group between 6 and 12 years [11], ing to a decline in the birth rate of thalassemia major in and hemoglobin level < 13g/dl in male and < 12 g/dl in some countries [5]. It has been estimated that one thou- female in the age group more than 12 years [12]. Mean sand children out of 1.5 million live births are born each corpuscular volume (MCV) of less than 80 fl and/or year suffering from thalassemia in Egypt [6]. It is re- mean corpuscular hemoglobin (MCH) of less than 27 pg ported that the carrier rate in Egypt is between 9 to 10% are generally used as cut-off points for further screening of the population [7]. with serum ferritin to exclude iron deficiency anemia. In Egypt, despite the high prevalence of β thalassemia Serum ferritin less than 15 ng/ml is considered diagnos- carriers and the growing number of patients born each tic of iron deficiency [13]. Blood samples of participants year, there is no national thalassemia prevention pro- with normal serum ferritin were analyzed by high per- gram [8]. Few studies were performed to assess the car- formance liquid chromatography (HPLC) for quantita- rier rate of β thalassemia [9, 10]. Selective screening tive estimation of an elevated HbA2 level, using the approach within the families suffering from thalassemia hemoglobin analyzer ARKRAY ADAMS A1C HA-8180T is ideal and more feasible in highly prevalent regions (Japan) device. HbA2 < 3.5% is considered diagnostic of with limited resources. The aim of our study was to de- β thalassemia carrier state [14]. termine β thalassemia carriers, in addition to iron defi- ciency anemia, individuals among relatives of β 2.3.1 Sample collection and storage thalassemia patients, especially in population crowded Five milliliters of whole blood were collected from every regions, for raising the awareness of the problem among subject into three vacutainer tubes. The first tube con- this high-risk population. taining EDTA was used as an anticoagulant for a complete blood picture (CBC) and 2 mm into a second 2 Methods tube for high performance liquid chromatography 2.1 Study design and setting (HPLC). The third tube was used for serum ferritin The current study is a cross-sectional multi-center study measurement for participants with hypochromic micro- conducted on 2118 relatives of patients with β thalas- cytic anemia. semia from different Egyptian governorates in the Mid Delta region (Al-Gharbia, Al-Dakahlia, Al-Menuofiea, Al-Sharkhia, Kafer el-Sheikh, Al-Beheira, and 2.4 Statistical analysis of data Alexandria). The collected data were coded, verified for complete- ness, recorded in a Microsoft Excel master sheet, and 2.2 Participants then statistically analyzed utilizing the SPSS™ (Statistics The study participants represented respondents who Program for Social Studies) software version 25 pro- were eligible and agreed to participate in the study from duced by IBM, Chicago, IL, USA. Means and standard the relatives (2nd, 3rd, and 4th degree) of all known β deviations were used to describe numerical values, while thalassemic children attending hematology/oncology frequencies were used for categorical ones. clinics at Tanta, Zagazig, Mansoura, Menuofia, and The Chi-square test was used to test the differences Alexandria Universities’ Hospitals during the 48 months between categorical variables, while the Mann-Whitney of the study (from 2016-2020). According to Egyptian U test was used for independent quantitative variables. P El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 3 of 8 value was considered significant at < 0.05 and < 0.001 total number of participants in this study was 2118 chil- for highly significant results. dren. Males constituted 936 participants (45.47%) while 54.53% (1155) were females. Participants with hypochro- 3 Results mic microcytic anemia constituted 1123 (53.02%). Figure 1 shows the screening algorism among the close Table 1 illustrates the prevalence of iron deficiency relatives of patients with confirmed β thalassemia. The anemia and β thalassemia carriers among the study Fig. 1 Screening algorithm for the participants El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 4 of 8 Table 1 Prevalence of iron deficiency anemia and β thalassemia carriers among studied relatives in Mid Nile Delta Egyptian Governorates (2016-2020) Governorate Total examined Iron deficiency anemia β thalassemia carrier (Group 1) (Group 2) NN % N % Al-Gharbia 182 82 45.05 56 30.77 Al-Menoufia 300 65 21.67 75 25.00 Al-Sharkia 265 13 4.91 136 51.32 Al-Dakahilia 668 100 14.97 248 37.13 Al-Beihera 219 22 10.05 70 31.96 Alexandria 326 69 21.17 108 33.13 Kafr-Elsheikh 158 13 8.23 66 41.78 Total 2118 364 17.19 759 35.84 χ 154.32 50.36 ** P < 0.001 0.001** **Highly significant (P < 0.01) participants in relation to the governorate of residence. The Table 3 shows the comparison of serum ferritin and totalprevalenceofirondeficiencyanemiaamong closerela- HbA2% between relatives who are β thalassemia carriers tives of confirmed β thalassemia patients in the Nile Delta and those with iron deficiency anemia. Serum ferritin region was found to be 17.19%. The highest prevalence of shows a significantly lower mean of 8.20 ± 3.78 ng/ml iron deficiency anemia (45.05%) was reported in Al- among group 1 than 68.73 ± 49.33 ng/ml among group Gharbia Governorate, followed by Al-Menoufia Governor- 2(p = 0.001). In comparison, the group’s 2 hemoglobin ate (21.67%) and the lowest prevalence was that of Al- A2% was significantly higher (4.55 ± 0.5) % compared to Sharkia Governorates (4.91%), these differences were highly the mean of 2.54 ± 0.49% detected among group 2 (p < statistically significant (p < 0.001). On the other hand, the 0.001). total carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia 4 Discussion Governorates (51.32%), followed by Kafr-Alsheikh Gover- Symptomatic β thalassemia syndromes constitute a sig- norate (41.78%), and Al-Dakahilia (37.13%). Al-Menoufia nificant public health problem in Egypt; the high preva- Governorate had the lowest prevalencerate(25.00%). These lence of beta thalassemia carriers, combined with a differences were also found highly statistically significant (p growing number of newly born cases, underscores the < 0.001). critical significance of developing a beta thalassemia pre- Table 2 demonstrates a comparison of blood indices vention program in Egypt [15]. Prevention by carrier de- between β thalassemia carriers and iron deficiency tection is needed in populations with a high incidence of anemia of the studied relatives. Only hemoglobin con- the disease, such as Egypt. Improving public awareness centration showed no significant difference between the and mandatory premarital screening for carrier detection two groups (p = 0.152). The total number of red blood 6 3 are essential to offer prenatal diagnosis and genetic corpuscles among group 2 (5.28 ± 0.63) × 10 /mm was counseling for high-risk couples [15]. significantly higher than that recorded for children with 6 3 Various approaches of carrier screening programs the group 1 (3.74 ± 0.56) × 10 /mm (p = 0.001). The were conducted in several countries. They include gen- mean hematocrit percentage in group 2 (33.31 ± 4.09) % eral population screening, high-risk group screening, was significantly higher than that of group 1 (32.7 ± antenatal screening, and cascade screening or extended 3.71) (p = 0.001). Besides, mean corpuscular volume was family screening [16]. As an autosomal recessive disease, significantly higher among group 1 (67.83 ± 7.21) fl together with the high rate of consanguineous marriages compared to group 2 (62.42 ± 6.37) fl (p = 0.001). The in our country, the expected highest prevalence of β same applies for MCH, 22.70 ± 2.81 versus 20.32 ± 2.21 thalassemia carriers will be among the patient’s relatives pg (p = 0.001); MCHC, 33.94 ± 2.32 g/dl versus 32.83 ± who are a good target for screening. This type of screen- 2.31 g/dl (p = 0.001). ing may offer an alternative to population screening for Lastly, group 1 had a significantly higher mean red cell identifying present and future couples at risk for produ- distribution width, 16.89 ± 2.28%, compared to 15.30 ± cing affected children [17]. 2.18% for group 2 (p = 0.001). El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 5 of 8 Table 2 Complete blood count of β thalassemia carriers and iron deficiency anemia participants in Mid Nile Delta Egyptian Governorates (2016-2020) Variable Iron deficiency anemia β thalassemia carrier MW P (Group 1) (Group 2) 6 3 Red blood corpuscles (X10 /mm ) Mean ± SD 3.74 ± 0.56 5.28 ± 0.63 13.45 0.001** Range 2.30-4.96 4.00-6.60 Median 3.80 5.28 Hemoglobin (g/dl) Mean ± SD 10.60 ± 1.21 10.95 ± 1.20 1.43 0.152 Range 6.60-12.90 9-15.40 Median 10.80 10.90 Hematocrit value (%) Mean ± SD 32.7 ± 3.71 33.31 ± 4.09 2.34 0.019** Range 18.50-39.7 20.20-44.90 Median 32.70 33. 10 Mean corpuscular volume (fl) Mean ± SD 67.83 ± 7.21 62.42 ± 6.37 7.70 0.001** Range 45-79 45.0-79.0 Median 69.00 62.00 Mean corpuscular hemoglobin (pg) Mean ± SD 22.70 ± 2.81 20.32 ± 2.21 7.20 0.001** Range 14.60-27 15.20-27.20 Median 22.75 20.10 Mean corpuscular hemoglobin concentration (g/dl) Mean ± SD 33.94 ± 2.32 32.83 ± 2.31 3.95 0.001** Range 29.50-38.20 26.80-37.80 Median 34.00 32.30 Red cell distribution width (%) Mean ± SD 16.89 ± 2.28 15.30 ± 2.18 5.93 0.001** Range 11.90-21.30 11.00-18.40 Median 17.4 16.00 SD standard deviation MW: Z value of Mann-Whitney U test **Highly significant (P < 0.01) The current study involved 2118 relatives of patients (67.59%), with a prevalence rate of 35.84% among the with β thalassemia from different Egyptian governorates studied relatives of the patients. This is about 3-4 times in the Mid Delta region. Microcytic hypochromic higher than the estimated carrier rate of 9-10% in the anemia was diagnosed in 53.02% of the studied groups. general population [7]. This result supports what was Carrier detection in this study was based upon the pres- previously reported that β thalassemia carriers are more ence of microcytic hypochromic anemia, normal serum prevalent in siblings of thalassemia major than the nor- ferritin level together with HbA2 level of < 3.5% [14]. mal population [18]. Most of the previous studies in- β thalassemia carrier state constituted the majority cluded general population and pregnant women among children with microcytic hypochromic anemia screening, with few that included relatives of thalassemia Table 3 Serum ferritin and HbA2 of β thalassemia carriers and iron deficiency anemia participants Mid Nile Delta Egyptian Governorates (2016-2020) Variable Iron deficiency anemia β- thalassemia carrier MW P (Group 1) (Group 2) ** Serum ferritin (ng/ml) Mean ± SD 8.20 ± 3.78 68.73 ± 49.33 23.35 0.001 Range 1.00-14.90 15.50-349 Median 6.85 55.00 ** Hemoglobin A2% Mean ± SD 2.54 ± 0.49 4.50 ± 0.59 23.36 0.001 Range 1.30-3.40 3.60-6.99 Median 2.60 4.500 SD standard deviation MW: Z value of Mann-Whitney U test **Highly significant (P < 0.01) El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 6 of 8 patients. To our knowledge, there is no published data below 15 ng/ml. In the present study, IDA was diag- about similar studies in Egypt. nosed in 17.19% of the participants. Though lower than Our estimated prevalence of β thalassemia trait (βTT) what was estimated in the general population, IDA is in relatives of patients is nearly similar to what was re- prevalent among relatives of thalassemia patients and ported in Rawalpind, Pakistan (31%) by Ahmed et al. should be searched for and adequately treated. The high- [19] while it is higher than the prevalence reported by est prevalence of IDA (45.05%) was reported in Al- Gorakshakar and Colah (21.9%) in extended family Gharbia Governorate, followed by Al-Menoufia Gover- screening in India [17]. On the other hand, it is lower norate (21.67%), and the lowest prevalence was that of than what was found in other studies done in Faisalabad Al-Sharkia Governorates (4.91%). The significant differ- (44.4%) [20], Kota (48.76%) [18], Bandung (59.6%) [21], ence between different governorates could be related to Karachi (62.2%) [22], Bhopal (76%) [23], and North India the involvement of rural areas in governorates with a (76.92%) [24]. This discrepancy could be explained by high prevalence of IDA, lower-income families with lim- the differences in general prevalence rate in the geo- ited access to iron-rich foods, and inefficient utilization graphic areas involved, selection criteria in each study of available micronutrients as a result of infectious dis- (siblings only or extended family, the number of in- eases, particularly helminthic infections [28]. cluded individuals), and genetic heterogeneity of thalas- Comparing the hematological parameters of relatives semia gene. with βTT and those with IDA, no significant difference In this study, the highest carrier prevalence rate was was found regarding Hb level. In contrast, βTT relatives detected in Al-Sharkia Governorates and followed by had a significantly higher RBCs count, with significant Kafr-Alsheikh Governorate, Al-Dakahilia, while Al- lower MCV, MCH, MCHC, and RDW than IDA. Red Menoufia Governorate had the lowest prevalence rate. blood cell (RBC) count is known to be increased in both This variation between localities might be related to the thalassemia patients and carriers. It is considered a use- different rate of consanguineous marriage in different ful diagnostic adjunct because thalassemia has micro- Egyptian communities. In societies where the majority of cytic anemia, increasing the RBCs number. In contrast, couples are unrelated, genes for recessive disorders usu- other causes of microcytic anemias, including iron defi- ally run in families for many generations without mani- ciency anemia and anemia of chronic disease, are typic- festing through the birth of an affected child. By ally associated with a proportional decrease in the RBC contrast, gene variants are trapped within extended fam- number [29]. ily members [19]. Thus, in communities where consan- In accordance with our results, a high RBC count guinity is evident, one can identify even more carriers among BTT was reported by Demir et al. [30], Vehapo- [16]. It was reported that the cascade screening result glu et al. [27], and Jameel et al. [31]. Demir et al. [30] re- was more impressive in a small location. ported that RBC count is one of the most reliable For example, in Sardinia, by analyzing 11% of the discrimination indices in differentiation between βTT population, more than 90% of the “at risk” couples were and IDA, with 90% of the patients were correctly identi- detected [25]. An affected child is a predictor of high fied with RBC count. The majority of β thalassaemia car- genetic risk, and an extended family study may discover riers have reduced MCV and MCH levels in the several carriers and couples at risk before marriage or standard complete blood examination (FBE) [31]. Low reproduction [17]. Family studies provide a highly effect- MCV is the key indicator for diagnosis and screening for ive risk detection approach. Population screening is less thalassemia. It was suggested that an MCV of < 72 is effective, but carrier follow-up will detect elevated risk maximally sensitive and specific for the presumptive prior to any affected child’s birth. Moreover, the perfect diagnosis of thalassemia [32]. approach is to provide both family studies and premari- The red cell distribution width (RDW) index reflects tal or antenatal screening for the relatives of affected the heterogeneity in the size distribution of erythrocytes, children [19]. measuring the coefficient of variation around MCV [33]. Worldwide, beta thalassemia trait (βTT) and iron defi- It was found to be the most reliable index evaluated for ciency anemia (IDA) are the two most frequent causes discrimination between βTT and IDA, with 100% sensi- of microcytic anemia [26]. The differentiation between tivity and 92.6% specificity. This index can be used to ef- IDA and βTT is of prime importance, especially in these ficiently screen patients with microcytosis for further high-risk groups for being βT carriers [27]. Iron defi- hematologic studies to confirm β thalassemia [34]. ciency anemia is of high prevalence among Egyptian Normal RDW among βTT was also reported by other children. In the study performed by El-Beshlawy et al. studies [18, 35, 36]. So, microcytosis accompanied by a [9], about one-third of the studied population in upper high RBC count and normal RDW is highly suggestive & lower Egypt had IDA based on the presence of micro- of BTT [36]. A definitive differential diagnosis between cytic hypochromic anemia with serum ferritin level βTT and IDA is based on HbA2 electrophoresis, serum El-Shanshory et al. Journal of the Egyptian Public Health Association (2021) 96:27 Page 7 of 8 iron, and ferritin levels [37]. In this regard, relatives of Haidy M Ibrahim; Dalia M Abd Elwahab; Reham F El- Moghazy; Lamia M Morad; Sara S Allam; Osama M Hussien) who share in the data collection. thalassemia patients with βTT have a significantly higher Lastly, we would like to thank, the Science, Technology, and Development level of HbA2 with significantly higher serum ferritin Fund (STDF) for the support and establishment of the Delta Thalassemia levels than those diagnosed as IDA. HbA2 levels (> Center: Control and Prevention. 3.5%) are the most significant parameter for identifying Authors’ contributions beta thalassemia carriers [28]. In this study, those with This research was carried out in collaboration with all authors. βTT have HbA2 ranged between 3.60-6.99% with a Conceptualization: ME, LS, SY, SR, AM, HH, SA, AA, AD, and SE. Methodology: AH, MW, ZM, MG, AA, MS, FE, RE, IK, and SS. Formal analysis and mean value of 4.55 ± 0.59%. In similar studies, the mean investigation: ME, LS, SY SR, AH, AA, MS, and IK. Writing—original draft HbA2% levels were 11.93 ± 0.5% [21], 4.99 ± 0.64% [16], preparation: SY SR, AH; YA, and SS. Writing— revision and editing: ME, LS, and 5.24 ± 1.14% [18]. and SS. All authors read and approved the final manuscript. Funding 4.1 Limitations of the study This work was supported by the Science, Technology, and Development An important limitation is the unavailability of molecu- Fund (STDF) [Capacity building Grant Project number 12439]. lar diagnosis of thalassemia and genetic screening to de- termine the genetic profile for individuals to identify Availability of data and materials The research data is available upon a reasonable request to the carriers. Besides, carrier identification by premarital and/ corresponding author. or early antenatal thalassemia screening is not mandatory and is not commonly used in Egypt. As the Declarations current state of thalassemia reflects the increasing need Ethics approval and consent to participate for national preventive program to reduce morbidity and The experimental protocol for involving humans was following the national/ mortality associated with this disease, particularly given international/institutional boards and the Declaration of Helsinki. The Ethics the country’s limited resources and that thalassemia pre- Committee of the Faculty of Medicine, Tanta University approved the study, with a reference code number (3031/01/15). A written informed consent was vention is cost-effective. We recommend initiating a na- taken from each study participant. Confidentiality of participants’ information tional program for extended family screening of relatives was guaranteed. with beta thalassemia patients as a preparatory and Consent for publication promising step to establish a national prevention pro- Not applicable. gram utilizing the data collected from the screening. Competing interests 5 Conclusion The authors declare no competing interests. Thalassemia carriers have characteristic hematological Author details parameters with mild anemia with microcytic hypochro- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Gharbia, mic RBCs, increased red cell counts and normal RDW Egypt. Pediatric Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Pediatric Department, Faculty of Medicine, Alexandria that could help screening and together with HbA2 quan- University, Alexandria, Egypt. Pediatric Department, Faculty of Medicine, tification by Hb electrophoresis or HPLC, βTT can be Menoufia University, Shibin el Kom, Egypt. Pediatric Department, Faculty of easily diagnosed and screened for in high-risk groups Medicine, Mansoura University, Mansoura, Egypt. Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Clinical like family members and relatives of thalassemia pa- Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, tients. Family screening program by screening for micro- Egypt. Clinical and Chemical Pathology Department, Faculty of Medicine, cytic hypochromic anemia with increased RBCs reduced Alexandria University, Alexandria, Egypt. Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shibin el Kom, Egypt. Clinical MCV; MCH and normal RDW is a valuable and feasible Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, alternative to the population screening for detecting Egypt. Consultant of Biochemistry, Genetic Unit, Children Hospital, family members at risk of carrier state of βTT. Those Mansoura University, Mansoura, Egypt. Public Health and Community Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt. can be further identified by measuring HbA2. Received: 31 October 2020 Accepted: 16 August 2021 Abbreviations BTT: β thalassemia trait; CBC: Complete blood count; EDTA: Ethylenediaminetetraacetic acid; FBE: Full blood examination; Hb: Hemoglobin; HPLC: High performance liquid chromatography; IDA: Iron References deficiency anemia; MCH: Mean corpuscular hemoglobin; MCHC: Mean 1. Weatherall DJ, Clegg JB. 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Journal

Journal of the Egyptian Public Health AssociationSpringer Journals

Published: Oct 11, 2021

Keywords: Screening; Thalassemia carriers; Mid Delta; Egypt

References