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Brief report
Structural hemoglobinopathies: Analysis of 128 cases and their relevance in the diabetic control
Hemoglobinopatías estructurales: análisis de 128 casos y su relevancia en el control de la diabetes
Fernando Marques-Garcia
Clinical Biochemistry Department, Clinical University Hospital of Salamanca, Salamanca, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hemoglobinopathies are monogenic disorders with an autosomal recessive inheritance pattern&#46; They have the highest incidence of hereditary diseases in the world with an average incidence of 7&#37; and reaching 25&#37; in some regions&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Hemoglobinopathies are classified into two groups&#46; One group are produced by a deficient in the synthesis of globin chains &#40;thalassemias&#41;&#44; and other group are produced by changes in the amino acid sequence &#40;structural hemoglobinopathies&#41;&#46; Currently&#44; with the increased of migration flows&#44; hemoglobin variants are being observed in regions where previously they had not been detected&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a> which increases the need to know its impact in these regions&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Some studies have been carried out analyzing the impact of migratory flows in Europe on the incidence of hereditary diseases such as hemoglobin disorders&#46; Spain has the fourth highest rate of incidence of abnormal hemoglobin carriers with 1&#46;90&#37; in the general population and 0&#46;28&#37; of carriers in immigrant population&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">High performance liquid chromatography &#40;HPLC&#41; is one of the methods used for the measurement of glycated hemoglobin for diagnosis and monitoring of diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> HPLC separates hemoglobin fractions and provides a profile in which some abnormal hemoglobins can be detective&#46; In this way&#44; some hemoglobinopathies can be directly detected &#40;structural hemoglobinopathies&#41;&#46; Structural hemoglobinopathies makes that the retention times in the column are modified&#44; resulting in delay of the peak appearance&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a> or increased hemoglobin fraction A<span class="elsevierStyleInf">2</span> can indicated thalassemia &#40;but without extra peak&#41;&#46; Methods for determination of hemoglobin A1c &#40;HbA<span class="elsevierStyleInf">1c</span>&#41; have interference&#44; as hemoglobinopathies&#44; that is necessary know for the appropriated evaluated of the glycated hemoglobin value&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We have analyzed the results of glycated hemoglobin in 65&#44;000 patients performed by HPLC in our laboratory for the diagnosis and monitoring diabetes mellitus&#46; With this assay&#44; we can detect abnormal structural hemoglobins too&#46; The objective of this work has been to obtain the prevalence of structural hemoglobinopathies in the influence area of our laboratory&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">Our laboratory provides assistance to 350&#44;564 citizens &#40;2013&#41;&#46; The samples used in this study were obtained between January 2013 to January 2015&#44; and were sent to the laboratory for the determination of glycated hemoglobin&#46; During this period 65&#44;000 samples were analyzed by HPLC method in HA-8180 system &#40;HPLC-ARKRAY&#174;&#44; Menarini Diagnostics&#44; Italy&#41;&#46; In addition to measuring glycated hemoglobin&#44; we identify hemoglobin variants&#44; such as hemoglobins S and <span class="elsevierStyleSmallCaps">C</span> and other fractions of hemoglobin such as fetal hemoglobin and hemoglobin A<span class="elsevierStyleInf">2</span>&#46; The identified variants were collected daily to be informed&#46; Based on the HbA<span class="elsevierStyleInf">2</span> values&#44; &#946;-thalassemia carriers &#40;HbA<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#46;5&#37;&#41; were also assessed&#44; not &#945;-thalassemia carriers are valued because not be detected by chromatography&#46; Samples that presented uncertain chromatogram&#44; the variant hemoglobin was defined through acid&#47;alkaline electrophoresis &#40;alternative method&#41; in the Haematology Molecular Genetics Unit&#44; Clinical Laboratory&#44; Vall d&#8217;Hebron Hospital&#44; Barcelona&#44; Spain&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Statistical analysis data was performed using SPSS 20&#46;0 software &#40;IBM&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">One hundred and twenty eight samples with structural hemoglobin variants have been identified during the study period&#46; According to Kolmogorov&#8211;Smirnov test&#44; the age distribution of variants was accurate to normal distribution with a mean of 45 years&#46; Gender separation also fits to normal distribution with a mean of 44 and 46 years&#44; for men and women respectively&#46; The summary of the statistical parameters&#44; both for the total sample and the separation by gender are show in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">128 structural variants of hemoglobin observed shown an incidence of 0&#46;19&#37; &#40;1&#46;97&#8240;&#41; in relation to the total studied population&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Foreign population &#40;69 hemoglobinopathies of total&#41; mainly come from two geographical areas&#58; Sub-Saharan Africa and South America-Caribbean&#46; The rest of hemoglobinopathies &#40;59&#41; were detected in Spanish population&#46; Total of 10 different variants and one thalassemia were identified &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The most frequent structural hemoglobinopathy detected has been heterozygous hemoglobin S &#40;HbA&#47;HbS&#41; observed in 75 patients &#40;58&#46;6&#37;&#41; followed by heterozygous hemoglobin C &#40;HbA&#47;HbC&#41; in 21 patients &#40;16&#46;4&#37;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows other variants identified&#44; as well as their percentage in the total samples studied&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In Spanish population&#44; five families with a structural hemoglobinopathy have been identified&#46; All were heterozygous&#46; The hemoglobin variants detected were&#58; two families with HbA&#47;HbO-Padova&#44; one family with HbA&#47;HbC&#44; one family with HbA&#47;HbD-Punjab&#47;Los Angeles and one family with HbA&#47;HbS&#46; In foreign population&#44; one family with HbA&#47;HbS&#44; and three patients with HbS&#47;HbS were detected&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Most of the samples &#40;82&#59; 64&#37;&#41; with abnormal hemoglobin came from Primary Health Centers and the rest &#40;46&#59; 36&#37;&#41; from Hospital Services&#46; Of the 128 hemoglobinopathies&#44; 50 &#40;39&#37;&#41; had HbA<span class="elsevierStyleInf">2</span> value above 3&#46;5&#37;&#44; with a range between 3&#46;6&#37; and 5&#46;5&#37;&#46; This group includes representatives of all the structural hemoglobinopathies identified in our population&#44; except the HbD-Punjab&#47;Los Angeles&#46; Comparing population with hemoglobinopathies versus non-hemoglobinopathies have differences in VCM &#40;82&#46;2<span class="elsevierStyleHsp" style=""></span>fL versus 89&#46;5<span class="elsevierStyleHsp" style=""></span>fL&#41; value&#46; Hemoglobin values are similar between these groups &#40;13&#46;86<span class="elsevierStyleHsp" style=""></span>g&#47;L versus 13&#46;97<span class="elsevierStyleHsp" style=""></span>g&#47;L&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">A large amount of scientific evidence has accumulated indicating that hemoglobinopathies are a problem of public health in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Migratory flows are increasing the incidence of these diseases in regions with a low incidence of hemoglobinopathies&#46; In Europe&#44; which in recent years is experiencing a great migratory pressure&#44; the incidence of hemoglobinopathies is increasing significantly&#44; both in endemic regions to these diseases such as Southern Italy and Cyprus&#44; and in non-endemic regions&#46; Further&#44; a greater increase in the incidence is expected in the future&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a> In this way&#44; studies are needed to determine the current incidence of these diseases to develop strategies to reduce the cost for health systems and the morbi-mortality of patients&#46; It is necessary considered migratory flow in non-endemic areas&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">According to the data obtained in this study&#44; the incidence of hemoglobinopathies in our population is 0&#46;19&#37;&#44; while the estimated percentage of carriers of both structural hemoglobinopathies and thalassemias according to the migratory flow in our country is 1&#46;90&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> According to these data&#44; our region has a very low incidence compared with the estimated incidence in our country&#46; This situation may be due either to the fact that we only used samples sent to the laboratory for glycemic control or that our region has a lower immigration rate than other regions in Spain&#46; We have only analyzed structural hemoglobinopathies not thalassemias&#44; in this paper&#46; This may be an additional reason by we have obtained a lower incidence&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">On the other hand&#44; the structural hemoglobinopathies can interfere with HbA<span class="elsevierStyleInf">1c</span> value&#46; This is critical in the glucemic control in diabetic patients&#46; Nowadays&#44; the clinical laboratories have analytical methods for the identification of these variants with high precision&#46; Clinical laboratories use many different methods for measuring HbA<span class="elsevierStyleInf">1c</span>&#44; but some of these methods can give inaccurate results when patient has a hemoglobin variant&#46; So clinicians have known the method use in laboratory and interference based of hemoglobinopathies present&#46; In our laboratory&#44; we use ARKRAY<span class="elsevierStyleSup">&#174; ADAMS</span> HA-8180 HPLC method that only have significant interference with HbE and HbD&#59; and HbF when is higher of 30&#37;&#46; For situations in which the HbA<span class="elsevierStyleInf">1c</span> values are interfered&#44; measurement of other glycated proteins &#40;as fructosamine&#41; provides appropriate alternative to monitor therapy&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Further studies that estimate the true incidence of hemoglobinopathies in all suspected population are needed to more accurately assess the results obtained in this study and to obtain data on carriers of this disease in our region&#46; Approximately 40&#37; of the patients with hemoglobinopathies have thalassemia&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Screening to detect hemoglobinopathies is important not only in the neonatal population but also in the adult population to identify hemoglobinopathies carriers&#46; The Clinical Laboratory has informed these hemoglobin variants for adequate management of patients both a clinical level &#40;HbS&#41; as genetic council level &#40;if is necessary as heterozygous HbS and others&#41;&#46; These actions reduce the social impact of this structural hemoglobinopathies&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The author reports no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Keywords"
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        2 => array:2 [
          "identificador" => "xpalclavsec1473380"
          "titulo" => "Abbreviations"
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            0 => array:2 [
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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          "titulo" => "Discussion"
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          "titulo" => "Conflict of interest"
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        10 => array:2 [
          "identificador" => "xack584143"
          "titulo" => "Acknowledgements"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-09-16"
    "fechaAceptado" => "2020-11-05"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "HbA<span class="elsevierStyleInf">1c</span>"
            1 => "Hemoglobinopathies"
            2 => "Structural"
            3 => "Chromatography"
            4 => "Incidence"
            5 => "Interference"
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        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1473380"
          "palabras" => array:6 [
            0 => "HPLC"
            1 => "HbA<span class="elsevierStyleInf">1c</span>"
            2 => "HbE"
            3 => "HbD"
            4 => "HbF"
            5 => "VCM"
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          "palabras" => array:6 [
            0 => "HbA<span class="elsevierStyleInf">1c</span>"
            1 => "Hemoglobinopat&#237;as"
            2 => "Estructural"
            3 => "Cromatograf&#237;a"
            4 => "Incidencia"
            5 => "Interferencia"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hemoglobinopathies are monogenic disorders with autosomal recessive inheritance&#46; In Europe&#44; with increased migration flows these conditions are appearing more frequently in non-endemic regions&#46; HbA<span class="elsevierStyleInf">1c</span> testing is useful for evaluating long-term glycaemic status in diabetes mellitus patients&#46; During HbA<span class="elsevierStyleInf">1c</span> evaluation&#44; other hemoglobin fractions are detected&#44; such as structural hemoglobinopathies&#46; The principal objective of this work is to study the incidence of structural hemoglobinopathies in our area and their management&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Total population of 65&#44;000 patients for glycaemic monitoring was evaluated with HPLC equipment &#40;HPLC-ARKRAY&#174; ADAMS&#44; Menarini Diagnostics&#44; Italy&#41;&#46; This equipment quantifies different hemoglobin fractions&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We identified a total of 128 variants&#44; representing an incidence with respect to the study population of 0&#46;19&#37; &#40;1&#46;97&#8240;&#41;&#46; Most &#40;69&#41; were identified in the foreign population&#44; and the most frequent variant identified was heterozygous S hemoglobinopathy&#46; In six families&#44; structural hemoglobinopathy was identified&#46; Three patients with HbS&#47;HbS were detected&#46; Primary Health Centers were the origin of an important part of these variants &#40;82&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our study describes a low incidence for structural variants compared with the estimated incidence in Spain&#46; These variants can interfere with HbA<span class="elsevierStyleInf">1c</span> testing&#46; In these cases&#44; glycated protein study is an appropriate alternative to monitor diabetic therapy&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Las hemoglobinopat&#237;as son trastornos monog&#233;nicos de herencia autos&#243;mica recesiva&#46; En Europa se est&#225;n incrementando los flujos migratorios&#44; con mayor frecuencia de estas alteraciones en regiones no end&#233;micas&#46; La determinaci&#243;n del valor HbA<span class="elsevierStyleInf">1c</span> es &#250;til para evaluar el estatus gluc&#233;mico a largo plazo en pacientes diab&#233;ticos&#46; Durante la evaluaci&#243;n de la HbA<span class="elsevierStyleInf">1c</span>&#44; se detectan otras fracciones de la hemoglobina&#44; tales como las hemoglobinopat&#237;as estructurales&#46; El objetivo principal de este estudio fue estudiar la incidencia de hemoglobinopat&#237;as estructurales en nuestra zona&#44; as&#237; como su manejo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se evalu&#243; la monitorizaci&#243;n gluc&#233;mica en una poblaci&#243;n total de 65&#46;000 pacientes utilizando el equipo HPLC &#40;HPLC-ARKRAY&#174; ADAMS&#44; Menarini Diagnostics&#44; Italia&#41;&#44; el cual cuantifica diferentes fracciones de la hemoglobina&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Identificamos un total de 128 variantes&#44; que representan una incidencia con respecto a la poblaci&#243;n de estudio del 0&#44;19&#37; &#40;1&#44;97&#8240;&#41;&#46; La mayor&#237;a de ellas &#40;69&#41; fueron identificadas en la poblaci&#243;n extranjera&#44; siendo el heterocigoto hemoglobina S la variante m&#225;s frecuente&#46; En 6 familias se identificaron hemoglobinopat&#237;as estructurales&#46; Se detectaron 3 pacientes con HbS&#47;HbS&#46; Los centros de atenci&#243;n primaria fueron el origen de una parte importante de estas variantes &#40;82&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestro estudio describe una baja incidencia de variantes estructurales&#44; en comparaci&#243;n con la incidencia estimada en Espa&#241;a&#46; Dichas variantes pueden interferir en la determinaci&#243;n del valor de la HbA<span class="elsevierStyleInf">1c</span>&#46; En dichos casos el estudio de las prote&#237;nas glicosiladas es una alternativa adecuada para supervisar la terapia diab&#233;tica&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
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            "titulo" => "Material y m&#233;todos"
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            "identificador" => "abst0035"
            "titulo" => "Resultados"
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            "titulo" => "Conclusiones"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total population&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Female&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">&#40;a&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sample size&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">88&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age mean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">44&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>95&#37; CI for the mean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Different variants identified in our laboratory&#46; In addition to the variant&#44; the percentage of each to the total of identified and typical retention time observed in the chromatogram shown&#46;</p>"
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                      "titulo" => "The impact of migrations on the health services for rare diseases in Europe&#58; the example of haemoglobin disorders"
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                      "titulo" => "Hemoglobinopat&#237;as diagnosticadas en el &#225;rea sanitaria del Hospital Universitario Nuestra Se&#241;ora de Candelaria de Santa Cruz de Tenerife durante un a&#241;o"
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                      "titulo" => "Standards of medical care in diabetes"
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                            0 => "R&#46;W&#46; Grant"
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                            2 => "J&#46;E&#46; Fradkin"
                            3 => "C&#46; Hayes"
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                      "titulo" => "Haemoglobinopathies on the move&#58; is Europe ready&#63; Health and migration policy perspectives"
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                  "referenciaCompleta" => "US National Heart Lung and Blood Institute&#46; <a target="_blank" href="http://www.nhlbi.nih.gov/health/health%20topics/topics/thalassemia/">http&#58;&#47;&#47;www&#46;nhlbi&#46;nih&#46;gov&#47;health&#47;health topics&#47;topics&#47;thalassemia&#47;</a> &#91;10&#46;05&#46;20&#93;&#46;"
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        "texto" => "<p id="par0095" class="elsevierStylePara elsevierViewall">Alberto Diego PhD &#40;Menarini Diagnostics&#44; Italy&#41; for his constant willingness and collaboration&#46; The technical staff of our laboratory conducting the HPLC&#44; for their invaluable assistance and infinite patience&#46;</p>"
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Article information
ISSN: 00257753
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos