Psychological challenges and quality of life in Pakistani parents of children living with thalassemia.

PURPOSE: Children living with thalassemia experience psychological challenges, but despite significant psychosocial burdens, caregivers' psychological wellbeing and quality of life remain understudied, particularly in lower-and-middle-income countries. DESIGN AND METHOD: The current study evaluated these relationships in 100 male and female Pakistani caregivers (23-45 years; 61% female) using Ryff's Psychological Well-Being Scale and the Singapore Caregiver Quality of Life Scale. Caregivers completed questionnaires during regularly scheduled clinic visits for their child. RESULTS: We found that Pakistani caregivers in our sample generally had significantly lower (30-40 points) quality of life than a referent sample of caregivers of older adults (ps < 0.001). Self-acceptance and personal growth were consistently significant predictors across quality of life domains. Further, significant interactions were observed. Female caregivers with less self-acceptance had worse mental health and wellbeing and impact on daily life (p < .05). Male caregivers with less personal growth had worse physical health wellbeing (p < .05). CONCLUSIONS: Our results demonstrate the importance of considering how distinct aspects of psychological wellbeing, rather than just the overall score, relate to the specific quality of life domains among male and female caregivers. PRACTICE IMPLICATIONS: Pediatric nurses are at the frontline of service delivery for children and are in a prime position to observe caregivers who could be at high risk for psychological challenges. Given our findings, future clinical interventions should prioritize support services promoting personal growth and self-acceptance for Pakistani caregivers of children living with thalassemia.

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.

CAREST--Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia.

Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies.

Updates of the HbVar database of human hemoglobin variants and thalassemia mutations.

HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Database records include extensive phenotypic descriptions, biochemical and hematological effects, associated pathology and ethnic occurrence, accompanied by mutation frequencies and references. Here, we report updates to >600 HbVar entries, inclusion of population-specific data for 28 populations and 27 ethnic groups for α-, and ß-thalassemias and additional querying options in the HbVar query page. HbVar content was also inter-connected with two other established genetic databases, namely FINDbase (http://www.findbase.org) and Leiden Open-Access Variation database (http://www.lovd.nl), which allows comparative data querying and analysis. HbVar data content has contributed to the realization of two collaborative projects to identify genomic variants that lie on different globin paralogs. Most importantly, HbVar data content has contributed to demonstrate the microattribution concept in practice. These updates significantly enriched the database content and querying potential, enhanced the database profile and data quality and broadened the inter-relation of HbVar with other databases, which should increase the already high impact of this resource to the globin and genetic database community.

Molecular Epidemiological Survey of Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassemia in Uygur and Kazak Ethnic Groups in Xinjiang, Northwest China.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and thalassemia occur frequently in tropical and subtropical regions, while the prevalence of relationship between the two diseases in Xinjiang has not been reported. We aimed to determine the prevalence of these diseases and clarify the relationship between genotypes and phenotypes of the two diseases in the Uygur and Kazak ethnic groups in Xinjiang. We measured G6PD activity by G6PD:6PGD (glucose acid-6-phosphate dehydrogenase) ratio, identified the gene variants of G6PD and α- and ß-globin genes by polymerase chain reaction (PCR)-DNA sequencing and gap-PCR and compared these variants in different ethnic groups in Xinjiang with those adjacent to it. Of the 149 subjects with molecular analysis of G6PD deficiency conducted, a higher prevalence of the combined mutations c.1311C > T/IVSXI + 93T > C and IVSXI + 93T > C, both with normal enzymatic activities, were observed in the Uygur and Kazak subjects. A case of rare mutation HBB: c.135delC [codon 44 (-C) in the heterozygous state], a heterozygous case of HBB: c.68A > G [Hb G-Taipei or ß22(B4)Glu→Gly] and several common single nucleotide polymorphisms (SNPs) were found on the ß-globin gene. In conclusion, G6PD deficiency with pathogenic mutations and three common α-thalassemia (α-thal) [- -(SEA), -α(3.7) (rightward), -α(4.2) (leftward)] deletions and point mutations of the α-globin gene were not detected in the present study. The average incidence of ß-thalassemia (ß-thal) in Uygurs was 1.45% (2/138) in Xinjiang. The polymorphisms of G6PD and ß-globin genes might be useful genetic markers to trace the origin and migration of the Uygur and Kazak in Xinjiang.

The Changing Epidemiology of Pediatric Hemoglobinopathy Patients in Northern Alberta, Canada.

BACKGROUND: Hemoglobinopathies are associated with significant morbidity and mortality. Accurate epidemiologic data reflecting the number of hemoglobinopathy patients are lacking in Canada. Immigration patterns are shifting such that regions where these diseases were rare are seeing a rapid population expansion, revealing a gap in the health care system and the need for a public health response. METHODS: To understand the epidemiology of pediatric hemoglobinopathy patients given the provincial population growth and immigration patterns, a retrospective chart review was conducted at the Stollery Children's Hospital from January 2004 to July 2014. RESULTS: A total of 88% of patients had sickle cell disease; 55% of patients were Canadian born and 63% of families originated from Africa. There was a 3.5-fold increase in patient numbers with acceleration in patient accrual over the study period and a delay in diagnosis in 70% of patients. There was a significant increase in the number of hospitalizations over the study period. Thirteen percent required at least 1 exchange transfusion, 16% received chronic transfusions, and 30% of patients developed at least 1 severe complication related to their diagnosis. CONCLUSIONS: It is imperative to demonstrate the growing hemoglobinopathy population and changing health care requirements to advocate for appropriate resources, educate health care providers, and increase awareness.

The effect of thalassemia on erythrocyte reference intervals in a representative Han Chinese adult population.

BACKGROUND: The data from apparently healthy individuals with thalassemia has been demonstrated to have an effect on the reference intervals for the erythrocyte indices in areas with a high incidence of thalassemia. METHODS: Six clinical centers screened apparently healthy individuals using a questionnaire and a physical examination. Then, the qualified reference individuals were selected by hematological indices and a genotypic thalassemia diagnosis. Statistical comparisons were conducted for the erythrocyte reference intervals in the Chinese population with and without thalassemia. The constituent ratios and the mean (SD) of erythrocyte indices according to the thalassemia genotype were calculated. The relationship between the MCV values and the thalassemia genotype was also estimated. RESULTS: 4,636 reference individuals were included using hematological indices and genotypic thalassemia screening. The results of the erythrocyte reference intervals for individuals in Guangzhou with thalassemia demonstrated that the RBC, MCV, and MCH values significantly differed by gender compared with other regions (p < 0.01). In contrast, for individuals without thalassemia, the results tended to be similar and clinically acceptable. In addition, the results of the erythrocyte indices revealed significant differences among α-thalassemia patients, ß-thalassemia patients, and the control group. CONCLUSIONS: Apparently healthy individuals with thalassemia in the high prevalence zone of thalassemia could not be excluded by the questionnaire, physical examination or laboratory indices (Fe < 6 µmol/L, Hb < 90 g/L). The screening of genotypic thalassemia based on the MCV or MCH values to exclude unqualified individuals is the most effective way to obtain accurate and reliable reference intervals for the erythrocyte indices.

KLF1 gene mutations in Chinese adults with increased fetal hemoglobin.

We investigated the Krüppel-like factor 1 (KLF1) gene mutations in Chinese adults with increased Hb F levels (>1.5%) referred to our laboratory for thalassemia screening. Functionally effective KLF1 mutations were identified in five out of 140 samples with an elevated Hb F (1.9-11.4%). Only two different KLF1 mutations were detected. Functional KLF1 mutations were not identified in the matched cohort of 110 samples with normal Hb F values (<1.0%). The KLF1 mutations could be one of the causes of hereditary persistence of fetal hemoglobin (HPFH) in regions where thalassemias are common.

Molecular epidemiological survey of hemoglobinopathies in the Wuxi region of Jiangsu Province, eastern China.

In order to determine the prevalence and molecular characterization of hemoglobinopathies in the Wuxi region of Jiangsu Province in the People's Republic of China (PRC), a total of 10,297 healthy people selected from a regional hospital were screened. Hemoglobin (Hb) electrophoresis, complete blood cell (CBC) count, polymerase chain reaction (PCR), DNA sequencing, reverse dot-blot and multiplex ligation-dependent probe amplification (MLPA) were used to detect Hb variants, thalassemias and hereditary persistence of fetal Hb (HPFH). Two thousand and twenty-one adult subjects were screened for thalassemia, five cases were identified as α-thalassemia (α-thal) carriers including three cases of the -α(3.7) (rightward) deletion, one case of the - -(SEA) deletion and one case of ß-thal [IVS-II-654 (C>T), (HBB: c.316-197C>T)]. The incidence of Hb variants, thalassemia and HPFH/δß-thal were 0.136% (14/10,297), 0.25% (5/2021) and 0.0001% (1/10,297), respectively. Eight genotypes of Hb variants were found, including Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A], Hb J-Bangkok [ß56(D7)Gly→Asp (GGC>GAC); HBB; c.170G>A], Hb G-Coushatta [ß22(4)Glu→Ala (GAA>GCA); HBB: c.68A>C], Hb Queens [α34(B15)Leu→Arg (CTG>CGG) (α2 or α1); HBA2: c.104T>G (or HBA1)], Hb I [α16(A14)Lys→Glu, AAG>GAG (α1); HBA1: c.49A>G], Hb Beijing [α16(A14)Lys→Asn (AAG>AAC or AAT) (α2 or α1); HBA2: c.51G>C (or HBA1) or 51G>T (or HBA1)], Hb Ube-2 [α68(E17)Asn→Asp (AAC>GAC) (α2 or α1); HBA2: c.205A>G (or HBA1)] and Hb G-Taipei [ß22(B4)Glu→Gly (GAA>GGA); HBB: c.68A>G]. A Sicilian δß(0)-thal, identified for the first time in Asia, was also found in this survey.

Public perceptions and attitudes toward thalassaemia: Influencing factors in a multi-racial population.

BACKGROUND: Thalassaemia is a common public health problem in Malaysia and about 4.5 to 6% of the Malays and Chinese are carriers of this genetic disorder. The major forms of thalassaemia result in death in utero of affected foetuses (α-thalassaemia) or life-long blood transfusions for survival in ß-thalassaemia. This study, the first nationwide population based survey of thalassaemia in Malaysia, aimed to determine differences in public awareness, perceptions and attitudes toward thalassaemia in the multi-racial population in Malaysia. METHODS: A cross-sectional computer-assisted telephone interview survey of a representative sample of multi-racial Malaysians aged 18 years and above was conducted between July and December 2009. RESULTS: Of a total of 3723 responding households, 2846 (76.4%) have heard of thalassaemia. Mean knowledge score was 11.85 (SD ± 4.03), out of a maximum of 21, with higher scores indicating better knowledge. Statistically significant differences (P < 0.05) in total knowledge score by age groups, education attainment, employment status, and average household income were observed. Although the majority expressed very positive attitudes toward screening for thalassaemia, only 13.6% of married participants interviewed have been screened for thalassaemia. The majority (63.4%) were unsupportive of selective termination of foetuses diagnosed with thalassaemia major. CONCLUSION: Study shows that carrier and premarital screening programs for thalassaemia may be more effective and culturally acceptable in the reduction of pregnancies with thalassaemia major. The findings provide insights into culturally congruent educational interventions to reach out diverse socio-demographic and ethnic communities to increase knowledge and cultivate positive attitudes toward prevention of thalassaemia.

'He's the dad isn't he?' Gender, race and the politics of prenatal screening.

BACKGROUND: Men's involvement in prenatal screening is becoming increasingly important. However, despite the potentially significant role of fathers in haemoglobinopathy screening, their participation is under researched. Furthermore, the portrayal of Black and minority ethnic (BME) fathers tends to be based on persisting stereotypes of men as either absentee parents with limited roles in screening or as controlling decision-makers. OBJECTIVE: To describe the influence of ethnicity and gender on the process of participation of men in antenatal screening for sickle cell and thalassaemia. DESIGN: A qualitative study, using in-depth interviews and focus groups with 22 pregnant women from a range of socio-economic and ethnic backgrounds, 16 male partners and 15 midwives in a northern city in the UK. RESULTS: Men from BME groups take a pragmatic and equitable role in screening with their partners. White British men on the other hand, while willing to participate in screening, take a more casual view of their own direct participation. Accounts from hospital midwives supported these findings. CONCLUSIONS: While acknowledging the importance of material connections between certain BME groups and blood disorders, two key issues are raised. First, BME men's involvement contribute a challenge towards existing assumptions often made about BME fathers. Second, White British men's participation can be useful in determining the genetic status of the foetus and therefore their role should not be neglected. Screening research and practice need to broaden out their focus on issues of gender, ethnicity and screening.

The impact of thalassemia on Southeast Asian and Asian Indian families in the United States: a qualitative study.

OBJECTIVE: To describe the challenges, including sociocultural and socioeconomic barriers, faced by an urban immigrant population in the United States affected by thalassemia major. DESIGN: Ethnographic, semi-structured, 1-on-1 interviews using an interview guide developed for this study. Digital recordings were transcribed and data analyzed using constant comparative method. SETTING: University-based, Comprehensive Thalassemia Program at Children's Memorial Hospital, Chicago, IL, USA. PARTICIPANTS: Fourteen Southeast Asian and Asian Indian parents of children with transfusion dependent thalassemia. MAIN OUTCOME MEASURE: Qualitative descriptions of parental experiences, frequency of codes applied to interviews and emergent themes. RESULTS: Thalassemia has its greatest impact on the emotional and social well-being of affected children and their parents. Current and future concerns were related to disease-specific complications and challenges with management such as transfusions and chelation therapy. These perceptions were tied to parental hope for a cure, a frequently coded coping mechanism. Despite their availability, few parents relied on support systems beyond immediate family members due to perceived public knowledge gaps about thalassemia. Culturally based past experiences and barriers did not emerge as dominant themes in our analysis. CONCLUSION: The impact of thalassemia is tremendous for affected children and their parents and is due more to factors that were either disease-specific or common to other chronic disease models rather than those influenced by culture. The unmet needs of these families require additional investigation to facilitate the development of initiatives aimed at improving quality of life and lessening overall impact of thalassemia

Early prenatal diagnosis of thalassemia: the first report of experience in mainland China.

In this study, we report our experience with chorionic villus sampling (CVS) for prenatal diagnosis of thalassemia in mainland China. During a 4-year period, 308 pregnant women chose to have CVS for prenatal diagnosis. Chorionic villus sampling was successful in all cases, and post-CVS abortion was seen in only two cases (0.6%). DNA diagnosis was correctly done in 307 (99.7%) prenatal samples but maternal contamination was found in one (0.3%) subject. In total, 77 pregnancies were found with an affected fetus, and all of the affected pregnancies were terminated within 1 week after the CVS procedure. Our experience indicates that CVS is a feasible and effective technique for prenatal diagnosis of thalassemia.

Characterization of the 5' and 3' breakpoints of the Spanish (뫧)0-thalassemia deletion in Mexican patients.

We studied five unrelated Mexican carriers of the Spanish (δß)(0)-thalassemia [(δß)(0)-thal] mutation to characterize the size of the deletion, the 5' and 3' breakpoints and the 5' ß-globin haplotype. Sequence analysis revealed the presence of an 89,548 bp deletion. The δ- and ß-globin genes, two olfactory receptor genes (OR51V1 and OR52A1) and two pseudogenes (OR52Z1P and OR51A1P) were deleted. The 5' breakpoint was located at the same position as previously reported, and the 3' breakpoint was situated 7.0 kb downstream of OR52A1 and 11.7 kb upstream of OR52A5. The Spanish (δß)(0)-thal allele was associated with the 5' haplotype 2 [- + + - +] in the studied patients. Because this mutation is relatively frequent in Spain, and the Mexican population contains a high level of Spanish genetic background, we propose that the mutation in both populations share a common ancestral origin.

[Epidemiological study of thalasaemia among children in Xishuangbanna, Dehong and Nujiang of Yunnan province].

OBJECTIVE: To investigate the carrier rate of thalasaemia among the children of 10 minority ethnic groups in 3 border states (Xishuangbanna, Dehong and Nujiang) of Yunnan Province. METHODS: A total of 6562 samples of children under 10 years old were analyzed by blood cell automatic analysis and hemoglobin electrophoresis. RESULTS: The overall carrier frequency of thalasaemia was highest (46.2%) in Dehong, and lowest (30.6%) in Nujiang. The carrier frequency of beta-thalasaemia was the highest (40.6%) in Achang, and lowest (2.5%) in Dulong. The carrier frequency of alpha-thalasaemia was the highest (22.1%) in Dai from Xishuangbanna, followed by Dulong (19.1%). CONCLUSION: Thalasaemia carrier rates were high among the children of 10 minority ethnic groups in Yunnan. There were regional differences in their incidences. The results provide a valuable basis for thalasaemia prevention in Yunnan minorities in the three border states.

Thalassemia in Western Australia: 11 novel deletions characterized by Multiplex Ligation-dependent Probe Amplification.

The number of immigrants in Western Australia from many different areas where hemoglobinopathies are endemic has increased dramatically since the 1970s. Therefore, many different thalassemia mutations have been introduced in the country, which add a technological diagnostic problem to the serious burden of hemoglobinopathy management and to public health care. Recently, we have developed a rapid and simple technique based on Multiplex Ligation-dependent Probe Amplification to detect deletions causing alpha-and beta-thalassemia, deltabeta-thalassemia and Hereditary Persistence of Fetal Hemoglobin. A screening for (unknown) deletions was performed in a cohort of patients of different ethnic backgrounds preselected for their thalassemia phenotype, in which common deletions and point mutations were excluded. Out of 37 cases suspected to carry a deletion, 27 were found to carry 17 different deletion types of which 6 causing alpha-thalassemia and 5 causing beta-thalassemia were novel. For 3 of the deletions, we have been able to characterize the exact breakpoint sequences by long-range PCR and direct sequencing. These results show that MLPA is a suitable technology to detect unknown and uncommon deletions. These could represent a diagnostic problem when offering prevention to couples at risk presenting with unclear phenotypes and might result in a serious fetal problem when the deletion involves embryonic genes.

Symptoms of depression and anxiety in patients with thalassemia: prevalence and correlates in the thalassemia longitudinal cohort.

Thalassemia is an inherited blood disorder that requires lifelong adherence to a complicated and burdensome medical regimen which could potentially impact emotional functioning of patients. The importance of understanding and promoting healthy emotional functioning is crucial not only to psychological well-being, but also to physical health as it has been shown to impact adherence to medical regimens [1-4]. The current study aimed to [1] determine the prevalence of depressive and anxiety symptoms in adolescent and adult patients with thalassemia; and [2] explore possible demographic, medical, and psychosocial correlates of these symptoms in 276 patients (14-58 years old, M age = 27.83; 52% female). Overall, most patients did not report experiencing significant symptoms of anxiety and depression (33% of participants indicated experiencing symptoms of anxiety and 11% symptoms of depression). Females and older patients were more likely to experience these symptoms than males and younger patients. Symptoms of anxiety and depression were positively associated with self-report of difficulty with adherence and negatively associated with quality of life. Given these findings, regular screening for anxiety and depression symptoms could help to identify at-risk individuals to provide them with appropriate psychological support with the goal of improving both emotional and physical health.

Haematopoietic stem cell transplantation for thalassaemia in Chinese patients.

Beta thalassaemia major is a common hereditary haematological disease in southern Chinese. Advances in transfusion and iron chelation improve survival but haematopoietic stem cell transplantation (HSCT) is still the only curative treatment. Due to repeated blood transfusion and iron overload, thalassaemia patients undergoing HSCT are at a higher risk of graft rejection and transplant-related mortality. The prognostic factors identified to be affecting transplant outcome include hepatomegaly, hepatic fibrosis, and compliance to chelation therapy. Patients can be classified into three classes and conditioning regimens are modified according to the risk. Early stage patients have 85 to 90% chance of disease-free survival, whereas advance stage only has 60% disease-free survival. Mixed chimerism is common after HSCT but majority have satisfactory erythropoiesis without need for further transfusion. Sibling cord blood and bone marrow transplantation has similar outcome. Recently alternative donor transplant has been performed in patients without human leukocyte antigen (HLA)-identical siblings. The result of unrelated-donor bone marrow transplantation is in general inferior but extended HLA matching may improve outcome. The use of unrelated cord blood transplant from a single-centre study showed promising result. The survivors require iron depletion to remove excessive iron store and some may require hormonal replacement therapy. Most of the patients have good quality of life after successful HSCT.

Hemoglobin variants in Cyprus.

Cyprus, located at the eastern end of the Mediterranean region, has been a place of eastern and western civilizations, and the presence of various hemoglobin (Hb) variants can be considered a testimony to past colonizations of the island. In this study, we report the structural Hb variants identified in the Cypriot population (Greek Cypriots, Maronites, Armenians, and Latinos) during the thalassemia screening of 248,000 subjects carried out at the Thalassaemia Centre, Nicosia, Cyprus, over a period of 26 years. A sample population of 65,668 people was used to determine the frequency and localization of several of the variants identified in Cyprus. The localization of some of the variants in regions where the presence of foreign people was most prevalent provides important clues to the origin of the variants. Twelve structural variants have been identified by DNA sequencing, nine concerning the beta-globin gene and three concerning the alpha-globin gene. The most common beta-globin variants identified were Hb S (0.2%), Hb D-Punjab (0.02%), and Hb Lepore-Washington-Boston (Hb Lepore-WB) (0.03%); the most common alpha-globin variant was Hb Setif (0.1%). The presence of some of these variants is likely to be directly linked to the history of Cyprus, as archeological monuments have been found throughout the island which signify the presence for many years of the Greeks, Syrians, Persians, Arabs, Byzantines, Franks, Venetians, and Turks.