ABSTRACT
The prevalence of the Factor V Leiden (FVL; G1691A) mutation and the methylenetetrahydrofolate reductase (MTHFR; C677T) mutation was determined in 180 patients with sickle cell (SS) disease (126 sickle homozygous and 54 sickle ß-thalassaemia--age 1-47 years) and in 130 healthy controls. The FVL mutation in the heterozygous state was present in only 3 patients with SS disease and was absent in the controls. Genotyping of MTHFR 677C > T revealed increased frequency of the C allele than the T allele in patients as well as in controls. This suggests that these genetic markers may not be major risk factors for a hypercoagulable state in Indian patients with SS disease.
Subject(s)
Alleles , Anemia, Sickle Cell/genetics , Factor V/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Mutation, Missense , Adolescent , Adult , Anemia, Sickle Cell/epidemiology , Child , Child, Preschool , Female , Humans , India , Infant , Male , Middle Aged , Prevalence , Risk FactorsABSTRACT
OBJECTIVE: Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. METHODS: In this paper 127 sickle cell anemia patients and 58 patients with sickle-ß-thalassemia (median age 12 ± 8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. RESULTS: The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312). CONCLUSION: The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.
Subject(s)
Anemia, Sickle Cell/genetics , Receptors, IgG/genetics , beta-Thalassemia/genetics , Adult , Anemia, Sickle Cell/pathology , Child , Child, Preschool , Female , GPI-Linked Proteins/biosynthesis , GPI-Linked Proteins/genetics , Gene Expression , Humans , India , L-Selectin/genetics , L-Selectin/metabolism , Male , Neutrophils/metabolism , Neutrophils/pathology , Receptors, IgG/biosynthesis , beta-Thalassemia/pathologyABSTRACT
INTRODUCTION: Data on the efficacy of hydroxyurea (HU) in Indian children with sickle cell anaemia (SCA) is limited. Hence, we have evaluated the efficacy of fixed low dose HU in Indian children. METHODS: The study cohort consisted of 144 children (<18 years of age) with SCA having severe manifestations (≥ 3 episodes of vasocclusive crisis or blood transfusions, or having ≥ 1 episode of acute chest syndrome or cerebrovascular stroke or sequestration crisis) who were started on fixed low dose HU (10 mg/kg/day). They were followed up for two years and monitored for the hematological and clinical efficacy and safety. RESULTS: There was significant increase in the fetal hemoglobin level (HbF%), total hemoglobin and mean corpuscular volume. Vasoocclusive crises, blood transfusions, acute chest syndrome, sequestration crises and hospitalizations decreased significantly. Baseline HbF% had significant positive correlation with HbF% at 24 months. There was significant negative correlation between baseline HbF% and change in HbF% from baseline to 24 months. No significant correlation was found between HbF% at baseline and clinical event rates per year after HU. No major adverse events occurred during the study period. CONCLUSIONS: Fixed low dose HU is effective and safe in Indian children with SCA.