PubMed · 15658441
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Junko Murakami. 2004. [Abnormal Hb (hemoglobin)].. https://pubmed.ncbi.nlm.nih.gov/15658441/
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BACKGROUND AND OBJECTIVE: Hemoglobin S (HbS) alpha-thalassemia together with ss-thalassemia and hemoglobins C, E and D are named common hemoglobinopathies. In this study, we analyzed the frequency of the association between alpha-thalassemia and HbS and its phenotypic expression. PATIENTS AND METHOD: Since January 1995 to March 2003 we studied 83 cases of HbS, which were diagnosed by electrophoretic and chromatographic criteria. The molecular study was carried out by Southern blot with the restriction enzymes Bam HI and Bgl II and a (1.5 Kb Pst) and z (1.8 Kb Sac Y) probes. RESULTS: 45 cases (54.2%) had a-thalassemia (36 -alpha3,7/aa; 1-alpha4,2/alphaalpha; 6 -alpha3,7/-alpha3,7; 1-alpha4,2/-alpha4,2); 36 had not alpha-thalassemia and in two cases there were a triplication of a genes. The patients with HbS heterozygote associated with alpha-thalassemia showed a percentage of HbS (p < 0.0001), CMV (p = 0.004), MCH (p = 0.002) and MCHC (p = 0.02) significantly lower than the cases of HbS without this association. However, no differences between both groups were found with regard to the rest of parameters analyzed (Hb p = 0.56; PVC p = 0.84; RDW p = 0.06; Reticulocytes p = 0.26; HbF p = 0.76; HbA2 p = 0.13). In the cases with a severe form of disease (HbS homozygote; HbS/Hb C; HbS/beta-thalassemia), patients with alpha-thalassemia had a number of leukocytes that was significantly lower than that of patients without alpha-thalassemia (p = 0.034). CONCLUSION: An association between HbS and alpha-thalassemia was common (> 50%). Screening for this association is of great interest because the clinical expression in the cases of HbS homozigote will be modulated. This association must be suspected in cases of homozygous HbS in which levels of HbS are lower than expected.
The dominant assumption central to most treatments for sickle cell anemia has been that replacement of sickle hemoglobin (HbS) by fetal hemoglobin (HbF) would have major clinical benefit. Using laser photolysis, we have measured polymerization kinetics including rates of homogeneous and heterogeneous nucleation on mixtures of 20% and 30% HbF with HbS. We find that the present model for polymerization, including molecular crowding, can accurately predict the rates of such mixtures, by using the single assumption that no significant amount of HbF enters the polymer. The effects of replacing HbS by HbF on the rates of polymer formation are found to be significantly lower than previous measurements appeared to indicate because the impact of the replacement is also highly dependent on the total hemoglobin concentration. This is because the molecular crowding of non-polymerizing HbF offsets substantially the effects of decreasing the concentration of HbS concentration, an effect that increases with concentration. Most strikingly, the demonstrated benefit of hydroxyurea therapy in slowing the kinetics of intracellular polymerization cannot be primarily due to enhanced HbF, but must have some other origin, which could itself represent a promising therapeutic approach.
Sickle hemoglobin is a mutant hemoglobin in which valine has been substituted for the glutamic acid normally at the sixth amino acid of the beta-globin chain. Detection of the single base pair mutation at codon 6 of the beta-globin gene is important for the prenatal diagnosis of sickle cell anemia and sickle cell disease. Application of the polymerase chain reaction technology to detect sickle cell patients and heterozygous carriers in a group of patients suspected for sickle cell disease was carried out. The sample was composed of 52 normal individuals and 52 unrelated outpatients who were attending the Hematology Research Center. All patients were interviewed. Results of their medical histories, physical examination, and the hematological analysis were recorded. The blood samples were collected in EDTA and genomic DNA was extracted from leukocytes. An amplified 110 base pair fragment of the beta-globin gene containing codon 6, was digested with the restriction enzyme MS II, and electerophoresed in 3 per cent agarose. We have established the technical condition for detection of sickle cell disease using a PCR assay. Fifteen patients having haemoglobin (Hb SS) and 37 patients in the heterozygous state (Hb AS) were identified. We confirm that the normal controls have the Hb AA genotype. The standardization of a highly sensitive and specific diagnostic test for sickle cell disease permitted us to identify the normal controls, the homozygotes and heterozygotes. This amplification method is rapid, sensitive and simple, and also has application research that is important for the prenatal diagnosis of sickle cell disease.