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Background: Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India., Methods and Findings: Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS-δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies., Conclusion: A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations.

Objectives: Hydroxyurea is known to reduce ineffective erythropoiesis and thereby hemolysis leading to a reduction in bilirubin levels in patients with hemoglobinopathies. However, the effect of hydroxyurea on hyperbilirubinemia in relation to the UGT1A1 gene promoter polymorphism is not known in Indian patients with different hemoglobinopathies., Design and Methods: We studied 112 patients (77 sickle cell anemia, 22 β-thalassemia intermedia and 13 HbE-β-thalassemia) who were on hydroxyurea therapy for 2 years for their response towards hyperbilirubinemia associated with UGT1A1 promoter polymorphism., Results: The patients with (TA)(7)/(TA)(7) repeats had significantly higher serum bilirubin levels than those with (TA)(6)/(TA)(6) repeats in all the groups and the reduction in serum bilirubin after hydroxyurea therapy was still higher among patients with (TA)(7)/(TA)(7) repeats when compared with (TA)(6)/(TA)(6) repeats., Conclusions: Higher bilirubin levels were associated with the (TA)(7)/(TA)(7) sequence however they did not come down to normal levels after hydroxyurea therapy., (Copyright © 2010. Published by Elsevier Inc.)

Background: Haemoglobin E (HbE)-beta-thalassaemia has a very variable clinical presentation. The management of severe cases that are often transfusion dependent is similar to that of cases of beta-thalassaemia major; however, this is often not possible in India because of its high cost and the lack of availability of safe blood at many places. Thus there was a need for a drug such as hydroxyurea, which is known to reduce the transfusion requirements of patients with thalassaemia intermedia. This study was undertaken to evaluate the response of Indian patients with HbE-beta-thalassaemia to hydroxyurea., Materials and Methods: 11 patients with HbE-beta-thalassaemia receiving regular transfusion plus two less frequently transfused patients were selected for hydroxyurea therapy. Clinical and haematological evaluation was performed before and after treatment for 2 years. Molecular studies included beta-globin genotype, beta-globin gene haplotype, Xmn I polymorphism and alpha-genotyping., Results: Four clinically severe patients became transfusion independent (responders) after hydroxyurea therapy, four patients showed a reduction in their transfusion requirements (partial responders), and three patients were non-responders. Responders showed a statistically significant increase in Hb, mean corpuscular volume, mean cell Hb, fetal Hb and F cells with a reduction in their transfusion requirements. A reduction in serum ferritin concentration was also seen in responders and non-responders., Conclusions: Genetic markers such as Xmn I polymorphism and alpha-gene deletions were not always beneficial for the response to hydroxyurea therapy. Thus many more markers and a larger cohort need to be studied to predict the response in these patients.

Background: The clinical and hematological response to hydroxyurea was evaluated in beta thalassemia patients in western India with variable clinical severity and correlated with genetic factors., Materials and Methods: Seventy-nine patients-[38-beta thalassemia intermedia-(group I), 41-beta thalassemia major-(group II)] on hydroxyurea therapy were followed-up for 20-24months., Results: Among the frequently transfused patients in group I, 58% became transfusion independent and 16% showed a 50% reduction in transfusions after therapy which correlated with a higher mean fold increase in HbF and gamma mRNA expression levels. Forty-one percent of patients in group I had associated alpha-thalassemia and 72.7% were XmnI (+/+). beta thalassemia chromosomes among the responders of group I (41%) were linked to haplotype (- + + - + + - - +) as against haplotype (+ - - - - - - - +) being more common among the non-responders. Response was not linked to the beta thalassemia mutations. Thirty-two percent of group II patients showed a 50% reduction in their transfusion requirements after therapy which also correlated with a higher mean fold increase in HbF and gamma mRNA expression levels. A significant decrease in serum ferritin was seen in both groups. 19% of patients could not tolerate the drug., Conclusions: In group I, clinical response to hydroxyurea was better in patients with alpha-thalassemia, XmnI (+/+) and a higher mean fold increase in gamma mRNA expression. In group II, only one-third of patients showed a partial response.

The article presents two case studies of female patients with sickle-β thalassemia who were exposed to hydroxyurea during pregnancy. The authors assert that β thalassemia is prevalent in India and hydroxyurea (HU) is the drug of choice for the management of sickle cell disease patients. Hydroxyurea is know to be a teratogenic drug in research conducted on animals.