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Aguinaga

Bio: Aguinaga is an academic researcher. The author has contributed to research in topics: Hemoglobin A2 & Sickle cell trait. The author has an hindex of 1, co-authored 1 publications receiving 24 citations.

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Journal Article
TL;DR: The results show that the Hb A2 levels in Hb S-containing samples partially overlap with those expected from beta-thalassemia carriers, which should be aware of.
Abstract: In the sickle cell syndromes, Hb A2 measurements aid in the differential diagnosis of sickle cell anemia from sickle-beta-thalassemia. The purpose of this study is to assess the Hb A2 levels in samples containing sickle hemoglobin (Hb S) by the use of an automated high performance liquid chromatography system (HPLC-Variant beta-thalassemia Short Program). The blood samples analyzed were from individuals of African descent living in the state of Tennessee who had either sickle cell trait (Hb AS), sickle cell disease (Hb SS), or sickle cell-hemoglobin C disease (Hb SC). Interestingly, the Hb A2 levels determined by HPLC were found elevated in samples containing Hb S. The Hb A2 mean in Hb AS samples (n=146) is 4.09% (SD +/- 0.42, range 2.20 to 5.20%); in Hb SS samples (n=33) it is 3.90% (SD +/- 1.08, range 0.60 to 5.90%); and in Hb SC samples (n=27) it is 4.46% (SD +/- 0.70, range 2.30 to 5.91%). The Hb A2 mean by HPLC in normal individuals (Hb AA, n=70) is 2.57% (SD +/- 0.25, range 2.1 to 3.0%), and the Hb A2 range in beta-thalassemia carriers is 4 to 9%. Our results show that the Hb A2 levels in Hb S-containing samples partially overlap with those expected from beta-thalassemia carriers. The hemoglobinopathy laboratory should be aware of this apparent elevation in Hb A2 levels determined by HPLC in individuals carrying Hb S. Other factors, such as family history and clinical symptoms, should be taken into account before a diagnosis of sickle cell trait, sickle-beta-thalassemia, or sickle cell anemia is made.

27 citations


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Journal ArticleDOI
TL;DR: All apparatuses were able to identify carriers of high HbA2β‐thalassaemia carriers with the expected sensitivity and specificity in basic diagnostics of haemoglobinopathies.
Abstract: We have tested five haemoglobin (Hb) separation apparatuses, dedicated to haemoglobinopathy diagnostics. These are the four high performance liquid chromatography devices: VARIANT II, HA 8160, G7, Ultra(2) and the Capillary Electrophoresis apparatus from Sebia. In the first place, we focussed on the capacity of all apparatuses to detect the most common structural variants relevant for public health, these being HbS, HbC, HbE, HbD-Punjab and HbO-Arab. We then compared how the high HbA(2)beta-thalassaemia carriers were identified. All apparatuses were able to identify carriers of these traits with the expected sensitivity and specificity. With the primary goal of a high degree of conformity in basic diagnostics of haemoglobinopathies, we present the interpretation and the significance of the results on all apparatuses, and we comment on the unavoidable problems and solutions.

124 citations

Journal ArticleDOI
TL;DR: The Sebia Capillarys (capillary zone electrophoresis [CE] and the Primus Resolution high-pressure liquid chromatography (HPLC) were used to prospectively evaluate 297 samples for hemoglobinopathies and identified HbA2&prime and HbC together.
Abstract: The Sebia Capillarys (capillary zone electrophoresis [CE]) and the Primus Resolution high-pressure liquid chromatography (HPLC) were used to prospectively evaluate 297 samples for hemoglobinopathies. Hemoglobin (Hb) A levels were similar on both techniques (mean, 96.2% and SD, 5.7% by CE; mean, 96.8% and SD, 5.5% by HPLC), but HbA2 levels were higher by CE (mean, 2.8%; SD, 0.8%) than by HPLC (mean, 2.3%; SD, 0.8%). HbS had higher values by CE (mean, 40.6%; SD, 18.9%) than by HPLC (mean, 38.4%; SD, 18.9%). In cases with Hg S, HbA2 levels were greater by HPLC (mean, 4.0%; SD, 1.0%) than by CE (mean, 3.1%; SD, 0.8%). HbA2 was occasionally not separated sufficiently from HbC for measurement by CE, but did separate from HbE by CE. Both methods identified HbS, HbC, HbE, HbS, and HbC together, HbA2&prime, HbD-Los Angeles, HbF variant, HbG-Philadelphia, HbS-G Philadelphia, and Hb Lepore.

81 citations

Journal ArticleDOI
TL;DR: The native and posttranslationally modified globin chains in minor and major Hbs are unambiguously identified by MALDI-TOF MS.
Abstract: Background: Hemoglobin (Hb) heterogeneity arises mainly from posttranslational modifications of the globin chains, and cation-exchange chromatography reveals falsely increased concentrations of some minor Hbs in the presence of abnormal Hbs. Here we describe a method for identification of the globin chains and their posttranslational modifications contained in the Hb fractions. Methods: We used cation-exchange HPLC (PolyCAT A column) for separation of Hb fractions and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for analysis of the separated globin chains. Globin chains were identified by their molecular masses. Posttranslational modifications of globin chains were identified by digestion of the proteins with endoproteinase V8 before MALDI-TOF MS of the resulting peptides. Results: Analysis of the HbA2 fractions of patients with HbS revealed 4 different globin chains. We found, in addition to the expected α- and δ-chains, the carbamylated α- and the βS-chains. Additionally, we analyzed HbH, Hb Barts, HbA1b, pre-HbA1c, HbA1c, HbF1, HbF, HbA1d3a, HbA1d3b, HbA2, and HbC1 fractions from control and pathologic blood samples. We identified several posttranslational modifications of the globin chains, such as pyruvatization, glycation, acetylation, carbamylation, and acetaldehyde adduct formation. Conclusions: The native and posttranslationally modified globin chains in minor and major Hbs are unambiguously identified by MALDI-TOF MS. A minor Hb containing the carbamylated α- and the βS-chain elutes at the same time as normal HbA2 (α2δ2) and thus leads to falsely increased HbA2 values in patients with HbS when blood is analyzed with PolyCAT A chromatography.

57 citations

Journal ArticleDOI
TL;DR: Routine samples submitted for evaluation of hemoglobinopathy that demonstrated HbE were studied by high-pressure liquid chromatography and CE to provide an estimate of the range of HbA(2) in patients with Hb E when evaluated by CE.
Abstract: Capillary electrophoresis (CE) is capable of distinguishing hemoglobin E (HbE) from hemoglobin A(2) (HbA(2)), thus permitting quantification of HbA(2) in patients with HbE. In this study, routine samples submitted for evaluation of hemoglobinopathy that demonstrated HbE were studied by high-pressure liquid chromatography and CE. The data for 52 samples from adult HbE heterozygotes were compared with those for a control group consisting of 209 patients. The mean HbA(2) of patients with HbE trait was 3.4% (SD, 0.4%), which was significantly higher (P < .001) than the 2.6% (SD, 0.4%) for the control group. Seven samples from adults homozygous for HbE were also evaluated. The mean HbA(2) of HbE homozygotes was 4.4%, which was significantly greater (P < .001) than the HbA(2) values for the HbE heterozygotes. Data from these cases provide an estimate of the range of HbA(2) in patients with HbE when evaluated by CE.

39 citations

Journal ArticleDOI
TL;DR: HbA2, a tetramer of α‐ and δ‐globin chains, provides a diagnostic clue to the presence of β‐thalassaemia trait and may have a benefit in sickle cell disease similar to that of foetal haemoglobin.
Abstract: HbA2 , a tetramer of α- and δ-globin chains, provides a diagnostic clue to the presence of β-thalassaemia trait. This minor haemoglobin, which forms about 2-3% of the total, has no known physiological role, but has the interesting property of preventing polymerization of deoxy-sickle haemoglobin. If it were possible to increase the level of HbA2 sufficiently it could have a benefit in sickle cell disease similar to that of foetal haemoglobin. Moreover, HbA2 is present in all erythrocytes, an advantage not found with foetal haemoglobin, which is heterocellularly expressed. The molecular basis of HbA2 gene (HBD) expression is partially understood, and with new molecular tools, it might be possible to induce levels of HbA2 that could be clinically important. However, high concentrations of this positively charged haemoglobin might damage the erythrocyte membrane; also, the reciprocal relationship of δ- and γ-globin gene (HBD and HBG1/2, respectively) expression might negate any benefit of increasing transcription of the former.

30 citations