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Background & objectives: Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used drug, has shown promising results in the clinical management of SCD. The present systematic review was undertaken to assess the efficacy and toxicity of HU in Indian sickle cell patients. Methods: A systematic review of studies on HU therapy was conducted to identify the application of HU and its outcome(s) across India. PubMed, Scopus and Cochrane Library was used as data sources for various studies on the efficacy and toxicity of HU therapy for treatment for SCD in India published between January 2001 and October 2021. Two authors independently extracted the data on study design, patient characteristics and therapeutic outcomes of HU in order to determine the study quality of the present review. Results: Overall, 14 studies were included for a systematic analysis. Of these 11 were prospective, two cross-sectional and one double-blind randomized controlled trial. Low-dose HU (10 mg/kg/day) was found to reduce the rates of vaso-occlusive crisis and hospitalization as well as decreased the requirement of blood transfusion in SCD patients. The foetal haemoglobin (HbF) level was recorded in 13 (80%) studies all of whom reported an elevation in the HbF levels, with a mean increase in per cent HbF from 15.8 to 21.4 per cent across studies. The common adverse events were reversible, mild-to-moderate cytopenia and anaemia. Interpretation & conclusions: The findings of the present review suggest that there is still insufficient information presently to determine the long-term or major adverse effects on organ damage, fertility as well as pregnancy on the use of HU therapy for SCD. Long-term multi-centric studies are thus required to address these problems.
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Abstract In the 1960s Guthrie conceived the idea of preventing congenital disease using dried blood spot samples on filter paper to detect them through biochemical tests and then be able to treat environmental factors in time to avoid the devastating effect of the diseases. Uruguay started in 1994 with the detection of congenital hypothyroidism in umbilical cord blood. In 2007 it was extended to Phenylketonuria and Congenital Adrenal Hyperplasia, starting with dried blood spot sample. In 2008, with the incorporation of Mass Spectrometry, a pilot program was started for the detection of aminoacidopathies, beta-oxidation defects and organic acidemias disorders. In the following years, the program expanded to more diseases, reaching a total of 25 disorders that could be detected, 5 of them are investigated on a mandatory basis and others in pilot program. During the 25-year of experience, 974277 umbilical cord blood samples were analyzed and since 2007: 532684 dried blood spot samples. 613 true positive congenital disorders were identified. The coverage has been greater than 98% and the repetition rate for insufficient samples less than 1.9%.
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Background: Hemoglobinopathies are the commonest genetic disorders worldwide. Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease are the major disorders that require lifelong management and are to be considered for prevention. In India, Beta-Thalassemia is prevalent across the country, with an average frequency of carriers being 3-4%.Methods: This is a cross sectional study conducted between June 2016 - May 2017 in the Department of Medicine, RIMS Imphal in 453 patients as a workup for anemia and clinically suspected cases of Hemoglobinopathy or beta thalassemia. Blood samples were collected and sent for Haemoglobin Electrophoresis using cellulose alkaline technique.Results: Among the 453 cases of the population surveyed, 35% showed the presence of abnormal hemoglobin. 16% were found to be beta thalassemia carrier, 11.69% HbE trait, 6.62% Homozygous HbE, 0.4% beta thalassemia and 0.7% had Hereditary persistence of HbF.Conclusions: High prevalence of Beta Thalassemia trait occurred more frequently than other Hemoglobinopathies. The study concludes that it is immensely important epidemiologically to explore the haemoglobin variants in Manipur so that the carriers can be detected for prevention of more serious disorder in the future generations.
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Background: The present study was conducted to identify pattern distribution of abnormal haemoglobin variants by using HPLC method in a tertiary care hospital, Surat, Gujrat, India.Methods: A cross sectional study of one-year duration was conducted including 9,116 patients screened for the presence of abnormal haemoglobin variants. Blood samples were initially tested for solubility test and run on automated haemoglobin analyzer for complete haemogram. All the suspected and family study cases were processed for HPLC (Bio-Rad Variant II) for conclusive diagnosis. Patients with a history of recent blood transfusion of less than 3 months duration were excluded from the study.Results: A total of 9,116 cases (1390 males, 7726 females) were included in the present study. The age group of patients ranged from 1 month to 95 years. Solubility test and complete haemogram were performed in all the cases. Out of the 9,116 cases, 8409(92.24%)cases had normal HPLC pattern. 492(5.40%)cases were diagnosed as sickle cell trait, 176(1.93%) cases as sickle cell disease, 29(0.32%) cases as β thalassaemia trait, 1(0.01%) case as β thalassaemia major, 2(0.02%)cases as Hb E heterozygous and 03 (0.07%) cases as Hb D Punjab heterozygous. One case of double heterozygous for Hb E-β thalassaemia was also found.Conclusions: HPLC is a rapid, accurate and useful method for diagnosing haemoglobinopathies. It serves as an reliable tool in diagnosing the presence of abnormal haemoglobin variants in suspected cases on routine haematology in developing countries like India, where the resources for detection of haemoglobinopathies are limited. Early diagnosis may help in proper management of patients.
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Background: Beta thalassemia is the most common genetic disorder in India. Its trait, coinheritance and mutations vary from mild to severe condition, resulting in thalassemia minor (heterozygous), intermediate and major depending upon many factors. The objective of this study was to find out the prevalence rate and the carrier of beta thalassemia in population of Gujarat using molecular genetic analysis of beta thalassemia patients by targeted mutation assay (ARMS-PCR).Methods: A total 105 samples for beta thalassemia were analysed for IVS 1-5 (G→C) and CD 15 (G→A) mutations. These two common mutations of thalassemia in Gujarat were carried out using amplification refractory mutation system–polymerase chain reaction (ARMS-PCR) and gel electrophoresis method.Results: A total 105 samples referred to us for molecular genetic analysis. The occurrence of positive mutations of IVS 1-5 (G→C) and CD 15 (G→A) were found in 48 and 15 samples respectively. The rest were negatives.Conclusions: Present study concludes that the prevalence rate of Beta thalassemia was widespread among the Gujarat population. The identification of IVS 1-5 (G→C) and CD 15 (G→A) mutations was carried out. The analysis revealed that, mutational patterns of IVS 1-5 (G→C) was the most frequent among other mutations in Gujarat region.
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Background & objectives: Swiss-type hereditary persistence of foetal haemoglobin (HPFH) has been shown to be responsible for the wide range of F cell levels in healthy Thai adults. However, a survey for F cells in healthy Thai adults has not been performed. This study was conducted to determine the F cell distribution in adult Thai blood donors and to assess the possible involvement of ?-thalassaemia and haemoglobin E (HbE) carriers in increased HbF levels. Methods: Thai blood donors (n=375, 205 males and 170 females) were included in the study. Blood samples were collected for measuring haemoglobin (Hb) concentration and haematocrit (Hct) and F cell levels. Hb and Hct levels were determined by automated blood counter, while F cells were quantified by flow cytometric analysis of F cells stained by fluorescein isothiocyanate-conjugated anti ?-globin monoclonal antibody. Finally, F cell levels were compared between blood samples having mean corpuscular volume (MCV ) <80 fl and ?80 fl as well as between ?-haemoglobinopathies (HbE and ?-thalassaemia carriers) and normal adults. Results: F cell levels varied markedly spanning 0.80-39.2 per cent with a positively skewed distribution. Thirty two per cent of these individuals had F cell levels more than the 4.5 per cent cut-off point. F cell levels in females were significantly higher than those in males (P<0.05). F cell levels in individuals having MCV <80 fl were significantly higher than those having MCV ?80 fl (P<0.05). ?-haemoglobinopathy (HbE and ?-thalassaemia carriers) had significantly higher F cell levels than normal individuals (P<0.05). Interpretation & conclusions: The present results showed that besides Swiss-type HPFH, the ?-haemoglobinopathy was expected to be involved in increased F cell levels in adult Thais. Thus, influence of ?-haemoglobinopathy must be considered in interpreting F cell levels in area endemic of this globin disorder.
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Resumo Este artigo analisa a relação entre discursos médicos e noções cotidianas sobre raça, população e nação. Para isso, tomo como estudo de caso a comparação entre o uso dessas categorias na produção de artigos acadêmicos de dois renomados hematologistas brasileiros sobre a presença de hemoglobinas variantes patológicas no Brasil e a compreensão que famílias de pacientes diagnosticados com doença falciforme têm dessas mesmas questões. A comparação permite mostrar não só como os discursos da medicina influenciam o modo como questões relacionadas a raça e hereditariedade são compreendidas pelo público mais amplo, mas também a impossibilidade de separar em ambos casos, tanto na produção médica quanto nas falas dos pacientes, as noções sobre raça e hereditariedade de ideias mais amplas sobre o passado e o futuro da nação.
Abstract This article analyses the relationship between medical discourses and everyday notions of race, population and nation, using as case study the comparison between the use of these categories in medical articles of two renowned Brazilian haematologists on the presence of pathological variant haemoglobins in Brazil and the understanding of families of patients diagnosed with sickle-cell anaemia on the same questions. Through this comparison it is possible to see not only how medical discourses influence everyday notions of race and heredity, but also how in both cases these notions are inextricable from wider ideas about the past and future of the Brazilian nation.
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Humans , Male , Female , Racial Groups , Knowledge Bases , Genetics , HemoglobinopathiesABSTRACT
Haemoglobin S D-Punjab is a rare compound heterozygous haemoglobinopathy characterised by the presence of two β globin gene variants: β6(GAG→GTG) and β121(GAA→CAA). These patients’ clinical and haematological features mimic haemoglobin S disease. We describe the first case of doubly heterozygous HbSD-Punjab from Malaysia managed with regular blood transfusion at the age of one. This case highlights the propensity for occurrence of rare phenotypes within our multi-ethnic population and emphasises the importance of accurate genotyping to avoid erroneous counselling, and to plan an effective patient management strategy before complication evolves.
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Objective: Haemoglobinopathies are a group of disorders with structural or quantitative variation in normal hemoglobin structure. There are various identified haemoglobinopathies worldwide, among these sickle cell disease and beta thalassemia are prevalent in Gujarat. Both of them are associated with marked morbidity and mortality.Method: Hemoglobin electrophoresis is a low cost method helpful in early diagnosis of many of these haemoglobinopathies. In current retrospective study- 33 cases of clinically and hematological suspected cases of haemoglobinopathies were subjected for hemoglobin electrophoresis on agarose gel at pH 8.6. Result and conclusion: Out of 33 suspected cases 13 cases of thalassemia major, 10 cases of sickle cell anemia and 7 cases of sickle cell trait were diagnosed with varying degree of clinical and hematological findings.
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At present, prevention of thalassaemia and sickle cell disease is the only realistic approach to control the birth of new patients in countries having high numbers of carriers. This is fully justified because avoiding the birth of an ever increasing number of patients may allow a more effective use of the available resources in improving the management of the patients surviving today and alleviate the already overloaded public health system from the inevitable tremendous and ever increasing cost. Moreover, prenatal diagnosis may help couples at risk to have non-thalassaemic children. Greece is one of the countries where the mean frequency of carriers is approximately 7.5 per cent (population 11 million) and has set up a nationwide programme for carrier identification in the early seventies; this is provided through a dozen of specific Units attached to the major Blood Transfusion Services of the country, on a voluntary basis and free of charge. Spread of information through mass media, the schools, and other groups has greatly contributed in creating the necessary sensitization; obstetricians and antenatal Clinics are also instrumental to this effect. Prenatal diagnosis is offered centrally (Athens) and covers satisfactorily the estimated needs (500-600 annually); the total number has already exceeded 35,000. According to information obtained from the major paediatric hospitals all over the country, the number of thalassaemia major or SCD admitted for treatment over the last ten years has been around 15 yearly (instead of an estimate of 120-130).
Subject(s)
Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/prevention & control , Female , Greece/epidemiology , Genetic Carrier Screening , Humans , Pregnancy , Prenatal Diagnosis/methods , Public Health , Thalassemia/diagnosis , Thalassemia/epidemiology , Thalassemia/prevention & controlABSTRACT
Genetic counselling in tribals unlike general population residing in cities and near villages is a difficult task due of their lower literacy and poor socio-economic status. However, sustained effort is essential with a close interaction in the local language, certain misbeliefs need to be removed gradually taking into account their socio-cultural background. The present communication deals with our experience in counselling for haemoglobinopathies during Neonatal Screening Programme undertaken for sickle cell disease in Kalahandi district of Orissa and Community Screening Programmes in primitive tribes of India in four States viz. Orissa, Gujarat, Tamil Nadu and Maharashtra. Counselling during neonatal screening programme was very well accepted demonstrating the benefit to the small babies as regards the morbidity. Premarital marriage counselling was also accepted by them. The success rate as followed up for 5 years is almost 50 per cent, the limitation being long follow up. Genetic counselling in these areas has to be continuous to achieve success and therefore the need for setting up of permanent centres in the tribal areas in India.
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The thalassaemias and sickle cell disease are the commonest monogenic disorders in India. There are an estimated 7500 - 12,000 babies with β-thalassaemia major born every year in the country. While the overall prevalence of carriers in different States varies from 1.5 to 4 per cent, recent work has shown considerable variations in frequencies even within States. Thus, micromapping would help to determine the true burden of the disease. Although screening in antenatal clinics is being done at many centres, only 15-20 per cent of pregnant women register in antenatal clinics in public hospitals in the first trimester of pregnancy. There are only a handful of centres in major cities in this vast country where prenatal diagnosis is done. There is considerable molecular heterogeneity with 64 mutations identified, of which 6 to 7 common mutations account for 80-90 per cent of mutant alleles. First trimester foetal diagnosis is done by chorionic villus sampling (CVS) and DNA analysis using reverse dot blot hybridization, amplification refractory mutation system (ARMS) and DNA sequencing. Second trimester diagnosis is done by cordocentesis and foetal blood analysis on HPLC at a few centres. Our experience on prenatal diagnosis of haemoglobinopathies in 2221 pregnancies has shown that >90 per cent of couples were referred for prenatal diagnosis of β-thalassaemia after having one or more affected children while about 35 per cent of couples were referred for prenatal diagnosis of sickle cell disorders prospectively. There is a clear need for more data from India on non-invasive approaches for prenatal diagnosis.
Subject(s)
Anemia, Sickle Cell/diagnosis , Chorionic Villi Sampling/methods , Cordocentesis/methods , Female , Genetic Counseling , Genetic Testing/methods , Genetic Carrier Screening/methods , Humans , India , Pregnancy , Prenatal Diagnosis/methods , beta-Thalassemia/diagnosisABSTRACT
Genetic counselling is provided in places where genetic tests are carried out. The process involves pre-test counselling as well as post-test counselling to enable the individuals to face the situation and take appropriate decisions with the right frame of mind. Major ethical principles which govern the attitudes and actions of counsellors include: respect for patient autonomy, non-maleficence, beneficence, or taking action to help benefit others and prevent harm, both physical and mental, and justice, which requires that services be distributed fairly to those in need. Other moral issues include veracity, the duty to disclose information or to be truthful, and respect for patient confidentiality. Nondirective counselling, a hallmark of this profession, is in accordance with the principle of individual autonomy. High prevalence of haemoglobinopathies with availability of good and sensitive carrier detection tests and prenatal diagnostic techniques makes these good candidates for population screening of carriers along with genetic counselling for primary prevention of the disease. Screening of the extended family members of the affected child, high risk communities and general population screening including antenatal women are the main target groups for planning a Haemoglobinopathy control programme. A critical mass of trained genetic counsellors who have understanding of the ethical issues and its appropriate handling with the required sensitivity is needed in India.
Subject(s)
Female , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Genetic Carrier Screening , Humans , India , PregnancyABSTRACT
Background & objectives: The usefulness of cation exchange high performance liquid chromatography (CE-HPLC) as a tool for detection of thalassaemia/haemoglobin variants was evaluated in a prospective study in a tertiary care centre in north India. We also tried to evaluate the effect of concurrent nutritional deficiency on the HPLC pattern in the local ethnic population. Methods: A total of 800 blood samples were analyzed on the Bio-Rad Variant HPLC system by β-thal short program. The retention times, proportion of the haemoglobin (%), and the peak characteristics for all haemoglobin fractions were recorded. Alkaline and acid haemoglobin electrophoresis was performed to document the identities of the haemoglobin variants, wherever necessary. Many cases were subjected to family studies for a definitive diagnosis. Results: Among 800 samples tested, 553 (69.1%) were found to have normal HPLC pattern. Apart from β- thalassaemia, nine additional variants were encountered; HbS (2.8%), HbE (2.5%) and HbD (1.1%) being the most common variants present. Other variants included Hb Q-India, Hb-Lepore, δβ-thalassemia/ HPFH, HbD-Iran, HbJ-Meerut and HbH disease. There was a significant decrease in the level of HbA2 associated with iron deficiency anaemia (IDA) (P=0.004) and increase in megaloblastic anaemia (P<0.001) among subjects with normal HPLC pattern. Interpretation & conclusions: HPLC was found to be a simple, rapid and reliable method for the detection of hemoglobin variants. An accurate diagnosis can be provided in majority of cases by use of retention time, proportion of total haemoglobin, and peak characteristics of HPLC. Haemoglobin electrophoresis and family studies play a valuable role in difficult cases. Concurrent nutritional deficiency also has an effect on HbA2 levels.
Subject(s)
Anemia/etiology , Chromatography, High Pressure Liquid/methods , Chromatography, Ion Exchange/methods , Female , Hemoglobinopathies/classification , Hemoglobinopathies/diagnosis , Hemoglobinopathies/etiology , Hemoglobins/analysis , Humans , India , Male , Malnutrition/complications , Prospective StudiesABSTRACT
O Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil, instituído em 1994 diagnosticou, até 2005, 76 crianças com hipotireoidismo congênito, 10 com fenilcetonúria e 25 com hemoglobinopatias, o que representou uma incidência de 1:2.595, 1:19.409, 1:4.120, respectivamente. Foram diagnosticadas 2.747 crianças com traço falciforme (1:37,5 nascidos vivos). A cobertura média do programa foi de 94,5 por cento. Houve uma considerável melhora nos parâmetros de avaliação da qualidade do programa no período, porém, sem atingir os índices ideais. Campanhas visando à maior divulgação da importância da triagem neonatal são necessárias para aumentar a cobertura e a instituição do 3º dia de vida do recém-nascido como sendo o Dia do Teste do Pezinho poderia contribuir para que idades mais precoces de tratamento fossem atingidas, melhorando o prognóstico das crianças acometidas.
The Neonatal Screening Program at the University Hospital of the Ribeirao Preto School of Medicine, São Paulo University, Brazil, was introduced in 1994. As of December 2005, congenital hypothyroidism had been diagnosed in 76 infants, phenylketonuria in 10, and hemoglobinopathies in 25, representing incidence rates of 1:2,595, 1:19,409, and 1:4,120, respectively. A total of 2,747 newborns had the sickle cell trait, i.e., were heterozygous for the sickle mutation (1:37.5 live births). The program's mean coverage during this period was 94.5 percent. There was major improvement in the parameters for evaluating the program's quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the program's coverage. Setting postnatal day 3 as the standard Day for the Heel Stick Test would help ensure treatment at earlier ages, thus improving prognosis for affected infants.