Factors associated with anaemia and iron deficiency among women of reproductive age in Northeast Thailand: a cross-sectional study.

BACKGROUND: Anaemia and iron deficiency (ID) affect women of reproductive age globally and considered to be a major public health problem in developing countries. This study determines the prevalence of anaemia and ID among women of reproductive age in urban northeast Thailand and examined the relative contribution of various risk factors to anaemia and ID in this population. METHODS: Three hundred ninety-nine non-pregnant women, aged 18-45 years, from three universities in northeast Thailand participated in this cross-sectional study. Selected socio-demographic, history of blood loss, usual consumption of red meat and tea/coffee, and anthropometric data were collected. Complete blood count including haemoglobin (Hb) concentration, serum ferritin (SF), C-reactive protein (CRP), and thalassemia were determined. Multiple logistic regressions were applied to identify the risk factors of anaemia and ID. RESULTS: Overall, 370 participants were included for data analyses after excluding women with severe/intermedia thalassemia diseases and/or those with positive serum CRP. The prevalence of anaemia, ID, and iron deficiency anaemia (IDA) were 28.4, 28.4, and 13.2%, respectively. Women with thalassemia had a higher prevalence of anaemia but a lower prevalence of ID than the women without thalassemia. By multiple regression analysis, ID [adjusted OR (AOR) = 4.9, 95% CI = 2.8-8.3], two α-gene defects (AOR = 8.0, 95% CI = 3.0-21.3) and homozygous Hb E (AOR = 8.5, 95% CI = 3.0-24.3) were identified as the potential risk factors of anaemia. Further, the odds of ID were significantly higher among women who donated blood within the past 3 months (AOR = 6.7, 95% CI = 2.8-16.3), and had moderate to a high amount of blood loss during menstruation (AOR = 2.2, 95% CI = 1.3-3.9). CONCLUSION: This study found a relatively high but differential prevalence of anaemia and ID among women of reproductive age with or without thalassemia. Only homozygous Hb E and two α-gene defects of thalassemia types and ID were the main factors contributing to anaemia. Recent blood donation, and moderate to a high amount of blood loss during menstruation were potential risk factors of ID in this population.

Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial.

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6-23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (-1·93 (95 % CI -1·88, -1·97)) v. placebo (-1·88 (95 % CI -1·83, -1·92)), and the opposite occurred among initially anaemic children (final mean LAZ -1·90 (95 % CI -1·86, -1·94) in MNP v. -1·92 (95 % CI -1·88, -1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

Thalassemia and Hemoglobinopathies in an Ethnic Minority Group in Northern Vietnam.

This study assessed thalassemia and hemoglobinopathies in a group of the Tay ethnic minority. Participants included 289 women of reproductive-age who enrolled in a pilot screening program for thalassemia conducted at six communities of Thai Nguyen Province, northern Vietnam. Standard procedures including complete blood count (CBC), hemoglobin (Hb) and DNA analyses were performed for all samples. The prevalence of thalassemia in 289 Tay women was 15.6% (gene frequency 0.078) for α0-thalassemia (α0-thal), 10.0% (gene frequency 0.050) for α+-thal, 7.3% (gene frequency 0.036) for ß-thalassemia (ß-thal), 2.4% (gene frequency 0.012) for Hb Constant Spring [Hb CS; α142, Term→Gln, TAA>CAA (α2), HBA2: c.427T>C] and 1.7% (gene frequency 0.009) for Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A]. Further analysis of ß-globin gene abnormalities identified four mutations including codons 41/42 (-TCTT) (HBB: c.126_129delCTTT), codon 17 (A>T) (HBB: c.52A>T), codons 71/72 (+A) (HBB: c.216_217insA), and -28 (A>G) (HBB: c.78A>G). The results hint at the remarkably high frequencies of severe forms of thalassemia that indicate a serious public health problem requiring further exploration, and most probably, also intervention within the country.

EE score: an index for simple differentiation of homozygous hemoglobin E and hemoglobin E-ß0-thalassemia.

BACKGROUND: The objective of the study was to describe a formula based on hemoglobin (Hb)A2 and HbF levels for differentiation of homozygous HbE and HbE-ß-thalassemia. METHODS: A total of 1256 subjects suspected for homozygous HbE or HbE-ß0-thalassemia were recruited at the ongoing thalassemia screening program at Khon Kaen University, Thailand. Hb analysis was done using capillary electrophoresis. Genotyping was based on DNA analysis. An arbitrary formula based on HbA2 and HbF was developed statistically for differentiation of the two conditions. Validation was carried out prospectively on another 139 subjects encountered at routine laboratory. RESULTS: Among 1256 subjects, Hb and DNA analyses identified cases with homozygous HbE (n=1076, 85.7%), HbE-ß0-thalassemia (n=140, 11.1%), HbE-δß0-thalassemia (n=30, 2.4%) and unknown HbE-related disorder (n=10, 0.8%). An inverse correlation between the amounts of HbA2 and HbF in HbE-ß0-thalassemia was observed. With differences in the amounts of HbA2 and HbF between the groups, an arbitrary score (7.3 HbA2+HbF) was developed where score above 60 indicated HbE-ß0-thalassemia. Application of this score on another 139 subjects showed accurate prediction of HbE-ß0-thalassemia with 100% sensitivity, 96.5% specificity, 85.7% positive predictive value and 100% negative predictive value. Successful application onto couples at risk was demonstrated. CONCLUSIONS: An established score should prove useful in the differentiation of homozygous HbE and HbE-ß0-thalassemia in routine setting and lead to a significant reduction in number of referring cases for molecular testing.

Genetic origin of α0-thalassemia (SEA deletion) in Southeast Asian populations and application to accurate prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.

α0-thalassemia of SEA deletion (-SEA) is common among Southeast Asian and Chinese. Using haplotype and phylogenetic analyses, we examined the origin of this defect in Southeast Asian populations. Study was done on both normal and α0-thalassemia alleles in 3 ethnic groups including 96 Thai, 52 Laotian and 21 Cambodian. Five SNPs encompassing the (-SEA) including (rs3760053 T>G), (rs1211375 A>C), (rs3918352 A>G), (rs1203974 A>G) and (rs11248914 C>T) were examined using high-resolution melting assays. It was found that 94.0% of Thai, 100% of Laotian and 100% of Cambodian α0-thalassemia alleles were linked to the same haplotype: the haplotype H4 (AAGC), representing an Asian specific origin. An G allele of the (rs3760053) was found to be in strong linkage disequilibrium with the α0-thalassemia allele in these populations. A multiplex PCR assay was developed to detect simultaneously the (-SEA) allele and genotyping of a linked (rs3760053) to improve accuracy of prenatal diagnosis of α0-thalassemia. Application of this multiplex PCR assay for routine prenatal diagnosis of α0-thalassemia in 12 families revealed a 100% concordant result with conventional gap-PCR assay. Therefore, a single genetic origin is responsible for the spread and high prevalence of the (-SEA) in the region. The multiplex PCR assay developed should provide a double-check PCR system for more accurate diagnosis and allow the monitoring of possible maternal contamination at prenatal diagnosis of this important genetic disorder.

Anemia in the Elderly in Northeastern Thailand: A Community-Based Study Investigating Prevalence, Contributing Factors, and Hematologic Features.

This community-based study investigated anemia prevalence and certain hematologic features and their possible relationships to thalassemia and iron deficiency (ID) in a population of older people in Northeastern Thailand. Participants included 319 apparently healthy individuals ranging in age from 60 to 98 years, whose current health status was assessed by means of personal interviews. Blood samples were also collected to determine the following parameters: red blood cell indices, serum ferritin, C-reactive protein, hemoglobin profiles, and the α0-thalassemia gene. Based upon established WHO criteria, the overall prevalence of anemia was found to be 47.7%, increasing from 39% within the age group of 60-70 years to 68% in those >80 years. Factors considered to be significant contributors to anemia were classified as ID (3.6%), thalassemia (56.2%), and "unknown" (40.1%). Overall, only 2.4% of participants exhibited any ID. Hematologic changes appear to correlate with age. Our findings provide not only baseline information, potentially useful for implementing appropriate control measures, but also an enhanced awareness and understanding of the factors contributing to anemia among the elderly in the region.

Molecular analysis of haemoglobin E in Southeast Asian populations.

Haemoglobin (Hb) E is the most common Hb variant in Asia where its gene frequency approaches 0.3 in some areas. We studied genetic background of Hb E genes among Southeast Asian populations. This study examined ß-globin gene haplotypes linked to haemoglobin E (Hb E) in diverse groups of Southeast Asian populations. The study was conducted on southern Thai (22 alleles), Cambodian (84 alleles), Laotian (120 alleles), Vietnamese (87 alleles) and Burmese (one allele) subjects. Results were compared with those of previous studies in northeast Thailand, the Yunnan of China, West India and Europe. Ten different haplotypes were observed. The four most common haplotypes were haplotypes 1 (- + - + + + -) and 2 (+ - - - - + -) on chromosomes with framework 2 and haplotypes 6 (- + - + + - +) and 7 (+ - - - - - +) on chromosomes with framework 3 variety. Phylogenetic analysis indicated that haplotype 1 is a relatively recent haplotype found in all populations, whereas haplotype 6 is found predominately in Cambodians. The results indicate that at least two genetic origins of Hb E are responsible for the high prevalence and spread of Hb E among Southeast Asian populations.

Nine known and five novel mutations in the erythroid transcription factor KLF1 gene and phenotypic expression of fetal hemoglobin in hemoglobin E disorder.

Hemoglobin E is the most common Hb variant found in South East Asia. Variation of Hb F expression in Hb E syndrome is associated with several genetic modifiers. We report several single nucleotide polymorphisms (SNPs), including nine known and five novel mutations of the Krüppel-like factor 1 (KLF1; an erythroid specific transcription factor) gene and determine their associations with phenotypic expression of Hb F in Hb E disorders. KLF1 mutations were examined using high resolution melting (HRM) assay and DNA sequencing in 575 homozygous Hb E, 278 heterozygous Hb E and 100 normal subjects. Fourteen mutations were mostly observed in subjects with elevated Hb F, including nine known mutations (G176AfsX179, T334R, R238H, -154 (C>T), A298P, S270W, R301H, -148 (G>A) and G335R and five novel mutations (Q217X, Q223X, Y290_S293del, K307N, and M358I). None of them, but the -148 (G>A), were observed in normal controls to have Hb F <1%. Combined KLF1 mutations with other SNPs including (G)γ-XmnI, BCL11A and HBS1L-MYB were associated with higher Hb F levels. KLF1 is therefore an important genetic factor associated with increased Hb F and in combination with other modifying factors could explain the phenotypic variation of Hb F expression in this common hemoglobinopathy.

Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-ß-Thalassemia in Northeast Thailand.

Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of thalassemia and genetic modifiers. We report the molecular basis of NTDT in hemoglobin (Hb) E-ß-thalassemia disease. This study was done in 73 adult patients encountered at the prenatal diagnosis center of Khon Kaen University, Northeast Thailand. Hematological parameters and Hb patterns were collected, and α- and ß-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/Gγ-XmnI polymorphism, rs2297339, rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined. Five ß0-thalassemia mutations and a severe ß+-thalassemia mutation in trans to the ßE gene were identified. No significant difference in hematological parameters was observed among ß-thalassemia genotypes. Coinheritance of α-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including Gγ-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate multiple genetic factors in NTDT patients and underline the importance of complete genotyping to provide proper management, make clinical predictions, and improve genetic counseling.

Molecular Heterogeneity of Thalassemia among Pregnant Laotian Women.

BACKGROUND AND AIMS: A pilot screening program for thalassemia was initiated in the Lao People's Democratic Republic. This study aimed to describe the genotype diversity and hematologic features of thalassemia among the participating pregnant women. METHODS: Blood samples of 411 pregnant Laotian women were collected. Hemoglobin (Hb) profiles were determined using a capillary zone electrophoresis system. Mutations of α- and ß-globin genes were investigated using a polymerase chain reaction and related techniques. RESULTS: As many as 26 different thalassemia genotypes including non-transfusion-dependent thalassemia, i.e. Hb E-ß-thalassemia, Hb H, and EA Bart's diseases, were identified. A variety of phenotypic expressions of hematologic features and Hb profiles were observed, including an unusual phenotype of Hb E-ß0 thalassemia with 89.1% Hb E, 1.6% Hb F, and 9.3% Hb A2. CONCLUSIONS: The remarkable genotype-phenotype diversity indicates a need for careful laboratory interpretation in order to provide appropriate genetic counseling and care to the Laotian population.

Thalassemia Screening Using Different Automated Blood Cell Counters: Consideration of Appropriate Cutoff Values.

BACKGROUND: To evaluate the use of MCV and MCH cutoffs for thalassemia screening in areas with a high frequency of thalassemia and hemoglobinopathies using different hematology analyzers. METHODS: Blood samples of known α(0)-thalassemia and ß-thalassemia carriers were analyzed to establish the appropriate cutoffs for each analyzer. These selected cutoffs were validated prospectively for screening of α-thalassemia, ß-thalassemia in combination with the dichlorophenolindophenol test for hemoglobin E on another 288 Thai and 325 Laotian students. Genotypes were defined by standard hemoglobin and DNA analyses. RESULTS: The appropriate cutoffs for the Sysmex XS-800i and Sysmex XN-1000, Coulter LH 780, and Pentra ES-60 were found to be 78 fL for MCV and 25 pg for MCH. These were 82 fL and 25 pg for the Cell-Dyn Ruby. Further validation on Thai and Laotian students revealed 100% sensitivity and specificity of higher than 80% for all analyzers. CONCLUSIONS: While using MCV in screening requires establishment of appropriate cutoffs, MCH appears to be applicable to all analyzers. Each analyzer should be evaluated and appropriate cutoffs should be established before application in the field.

PILOT SCREENING PROGRAM FOR THALASSEMIA IN A COUNTRY WITH LIMITED RESOURCES: A COLLABORATION MODEL BETWEEN CLOSE NEIGHBORING COUNTRIES.

Screening for thalassemia carriers should not only be conducted in middle-income countries but also can be possible in low-middle income countries, through cooperation of experienced professionals from middle income countries. We describe a collaborating model between two close neighboring countries in establishing such a screening program for thalassemia. After training and setting up of facilities, a total of 152 out of 187 hospital staff were screened as a pilot activity to encourage community participation. Referring system for sending blood samples to a reference center in Thailand was also established. Among 152 health staff, 12.5% α0-thal, 2% ß-thal and 13% Hb E carriers were found. Applying thalassemia screening to 411 pregnant women and 71 spouses, 5 couples at risk of bearing a child of thalassemia disease were identified. The thalassemia screening program has a sensitivity of 99.5%, specificity of 77%, positive predictive value of 73%, and negative predictive value of 99.5%. Thus, it is possible to operate a thalassemia screening program with acceptable performance in a low-middle income country (Lao People's Democratic Republic) with the cooperation of a referral center located within close proximity in a middle income country (Thailand).

A large cohort of ß(+)-thalassemia in Thailand: molecular, hematological and diagnostic considerations.

We report the molecular and hematological characteristics associated with a large cohort of ß(+)-thalassemia in Thailand. Study was done on 21,068 unrelated subjects referred to our center in northeast Thailand for hemoglobinopathies investigation. Among 21,068 subjects, 2637 (12.5%) were found to carry ß-thalassemia. Of these 2637 cases, 705 (26.7%) carried ß(+)-thalassemia with eight different mutations including 6 promoter mutations; NT-28 (A-G), NT-31 (A-G), NT-50 (G-A), NT-86 (C-G), NT-87 (C-A) and NT-90 (C-T) and two missense mutations; Hb Malay (codon 19; AAC-AGC) and Hb Dhonburi (codon 126; GTG-GGG). Hematological features of carriers with these ß(+)-thalassemia (n=528) were compared with those with ß(0)-thalassemia (n=309). Data for Hb E-ß(+)-thalassemia (n=177) were also presented along with Hb E-ß(0)-thalassemia in our series (n=94). All patients with Hb E-ß(+)-thalassemia were associated with mild thalassemia intermedia phenotypes. Most of the ß(+)-thalassemia carriers had elevated Hb A2 and mild hypochromic microcytosis, some demonstrated borderline MCV and MCH values which, could compromise carrier screening. Analysis of α/ß-globin mRNA ratio in representative cases with normal, Hb E trait, ß(+)-thalassemia trait, Hb Dhonburi trait and ß(0)-thalassemia trait demonstrated the average values of 1.1, 1.7, 2.1, 1.7 and 3.1, respectively which is helpful in identification and differentiation of the cases.

Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome.

The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A2 expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and -154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), -154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and -154 (C-T) mutations. Significant higher Hb A2 level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A2, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome.

Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis.

Although the molecular basis of variability of hemoglobin (Hb) F has been extensively examined in ß-thalassemia and sickle cell diseases, less study has been done on Hb E disorder. To address the variability of Hb F expression in Hb EE disease, we have examined multiple single nucleotide polymorphisms (SNPs) in the ß-globin gene cluster, BCL11A and HBS1L-MYB genes and determined their associations with Hb F levels in this syndrome. Study was done on 141 adult Thai individuals with homozygous Hb E. Hematological parameters were recorded and Hb F measured using Hb-HPLC analyzer. It was found in 26 cases that co-inheritance of α-thalassemia could lead to significant lower production of Hb F. Association of Hb F expression with the (G)γ-Xmn I polymorphism and other SNPs including rs2297339, rs2838513, rs4895441 and rs9399137 in HBS1L-MYB gene and rs4671393 and rs11886868 in BCL11A gene was therefore analyzed in the remaining 115 cases without α-thalassemia. It was found that 4 of these 7 SNPs including (G)γ-XmnI polymorphism (rs7482144), HBS1L-MYB (rs4895441) and (rs9399137) and BCL11A (rs4671393) were significantly associated with higher proportions of subjects with high Hb F (Hb F≥5%). The result demonstrated that multiple genetic modifying factors including T allele of (G)γ-XmnI polymorphism (rs7482144), G allele of HBS1L-MYB (rs489441), C allele of HBS1L-MYB (rs9399137) and C allele of BCL11A (rs4671393) are associated with increased Hb F and in combination could explain approximately 80% of the variation of Hb F in Hb EE disease in Thai population. Other genetic factors regulating Hb F expression in this common genetic disorder remains to be elucidated.

Hemoglobin Constant Spring is markedly high in women of an ethnic minority group in Vietnam: a community-based survey and hematologic features.

A community-based survey was conducted to determine the prevalence and gene frequency of Hemoglobin Constant Spring (Hb CS) and other forms of thalassemia among an ethnic minority in Vietnam. A total of 298 ethnic minority women, the Có-Tu, participated. Hematological parameters and hemoglobin profiles were analyzed using standard automated analyzers. Alpha- and beta-thalassemia mutations were identified using polymerase chain reaction (PCR) based technology. Of the 298 women, 141 (47.3%) carried thalassemia genes. Hemoglobin Constant Spring (Hb CS) is the most common with a markedly high frequency of 0.143 (overall prevalence=26.2%). The heterozygous state of Hb CS was found in one-fifth (20.5%) of women participating. Seven women (2.4%) were Hb CS homozygote. The overall prevalence for Hb E was 13.8%, and 10.7% for α(+)-thalassemia. Other forms of thalassemia included 0.67% ß-thalassemia, and 0.34% Hb Paksé. None of the participants had the α(0)-thalassemia gene. The study provides basic epidemiological information about Hb CS as well as other forms of thalassemia for a specific group of an ethnic minority in Vietnam. The data will be useful for further study on the distribution of thalassemia in Southeast Asia.

Molecular and hematological studies in a large cohort of α(0)-thalassemia in northeast Thailand: data from a single referral center.

α(0)-thalassemia is the most severe form of α-thalassemia alleles found among Southeast Asian and Chinese populations and can cause a fatal condition known as hemoglobin Bart's hydrops fetalis and hemoglobin H disease. In order to provide the molecular epidemiological characteristic of α(0)-thalassemia in northeast Thailand, a total of 12,525 blood specimens referred to our center at Khon Kaen University in northeast Thailand during October 2008 to January 2012 were studied. Hematological parameters were recorded and DNA deletions causing α(0)-thalassemia were examined by PCR related techniques. Among 12,525 samples examined, α(0)-thalassemia alleles were identified in 1,873 (15.0%) samples, including 1855 (14.8%) cases with Southeast Asian (--(SEA)) deletion and 18 cases (0.2%) with THAI deletion (--(THAI)). As many as twenty genotypes were encountered. Hb profiles and hematological parameters were comparatively presented. Data on prevalence, molecular features and phenotypic expression of α(0)-thalassemia should prove useful in a carrier screening and a prevention and control program of this common genetic disorder in the region.

Burden of anemia in relation to thalassemia and iron deficiency among Vietnamese pregnant women.

BACKGROUND AND AIMS: Information about the extent to which anemia is related to thalassemia and iron deficiency (ID) is not available in Vietnam. This study investigated the burden of anemia in relation to thalassemia and ID among Vietnamese pregnant women. METHODS: A cross-sectional study was conducted in Thua Thien Hue, Central Vietnam. Blood samples taken from 399 pregnant women with a gestational age <12 weeks were analyzed. Anemia was defined as Hb levels <11 g/dl, and ID as ferritin values <15 ng/ml. RESULTS: Out of 399 participants, 77 (19.3%) were anemic. While the prevalence of ID was 20.1%, the prevalence of ID anemia was 6.0%. The overall prevalence of thalassemia was 7.3%. Of the 77 anemic women, 24 (31.2%) had ID, and 20 (26.0%) had thalassemia genes. The rest (42.9%) were anemic due to unknown causes. CONCLUSIONS: The results indicate that ID remains a significant health burden among the study population, together with anemia caused by unknown factors. Thalassemias appear not to contribute to a great extent to anemia among Vietnamese pregnant women. Other causes need to be investigated further in order to develop an effective control program for anemia within the population.

Thalassemia and hemoglobinopathies in Thua Thien Hue Province, Central Vietnam.

A community-based assessment of thalassemias and hemoglobinopathies was conducted at the Thua Thien Hue Province, Central Vietnam. By cluster sampling, a total of 410 pregnant women attending the antenatal care service at 30 commune health centers were recruited consecutively from September 2011 to June 2012. Hemoglobin (Hb) analysis was performed using an automated Hb analyzer. α-Thalassemia (α-thal) genes were identified by polymerase chain reaction (PCR)-based techniques. Out of the 410 pregnant women, 2.7% carried α(0)-thal and 1.2% were ß-thal carriers. One woman with the - -(THAI) deletion was also found. Among the females under survey, structural Hb variants with 3.2% Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.78G>C] and 3.7% Hb Constant Spring [Hb CS; α142, Term→Gln, TAA>CAA (α2); HBA2: c.427T>C] were found. Assessing the frequency of thalassemias and hemoglobinopathies by ethnicity, Kinh (Vietnamese) and ethnic minority groups, Hb CS with a high frequency of 24.0% was observed in the ethnic minority groups. These results provide basic population-based information, are useful not only for implementing measures for prevention and control of thalassemias in the region but also for studying the importance of thalassemias and hemoglobinopathies in ethnic minorities within Southeast Asia.

Hemoglobin EE disease in young Laotian children: Hematologic features and the contributions of genetic variations to Hb F expression.

BACKGROUND: The wide variation in hemoglobin (Hb) F levels has been observed in patients with Hb EE disease. This study aimed to describe hematologic features and determine the effect of genetic variants on Hb F expression in young children with Hb EE disease. METHODS: Hematologic features and Hb profiles of Laotian children aged 6-23 months, who originally enrolled in the Lao-Zinc study, were retrospectively reviewed. Only children with Hb EE disease, as indicated by DNA analysis, were included in this current analysis. Genetic variants, including the G γ-XmnI polymorphism (C>T) of the HBG2 gene, the HBS1L-MYB intergenic region on chromosome 6, and the BCL11A on chromosome 2 as well as the mutations occurring on the Krüppel-like factor 1 (KLF1) gene, were examined. RESULTS: In total, 205 children were diagnosed as having Hb EE disease with Hb F ranged from 1.2 to 43.7%. Most of the children had mild to moderate anemia with a remarkable microcytosis. Analysis of the genetic variants revealed an extremely high frequency of the G γ-XmnI (93.7%). Applying multiple regression analysis adjusted for age, sex, and α-thal gene, a positive relation was observed for the rs4671393 (coefficient = 3.87, p = .005) and the rs2297339 (coefficient = 2.48, p = .046), but not the G γ-XmnI. A statistically non-significant relation was noted for the rs9399137 and the -154 (C>T) KLF1 mutation. CONCLUSION: Our findings provide insight into complex situation of Hb F variability in young children with Hb EE disease; and this can guide to appropriate care and counseling to affected families.