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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hemoglobin Camperdown [β104Arg→Ser] Detection During Hemoglobin A<sub>1c</sub> Measurement via Capillary Electrophoresis</title><author><name sortKey="Brunel, Valery" sort="Brunel, Valery" uniqKey="Brunel V" first="Valéry" last="Brunel">Valéry Brunel</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Caneiro, Patrick" sort="Caneiro, Patrick" uniqKey="Caneiro P" first="Patrick" last="Caneiro">Patrick Caneiro</name><affiliation><nlm:aff id="A2">Department of Medical Biochemistry, General Hospital-Jacques Monod, Le Havre, France.</nlm:aff></affiliation></author><author><name sortKey="Lahary, Agnes" sort="Lahary, Agnes" uniqKey="Lahary A" first="Agnès" last="Lahary">Agnès Lahary</name><affiliation><nlm:aff id="A3">Department of Hematology, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Hue, Guy" sort="Hue, Guy" uniqKey="Hue G" first="Guy" last="Hue">Guy Hue</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Thuillez, Christian" sort="Thuillez, Christian" uniqKey="Thuillez C" first="Christian" last="Thuillez">Christian Thuillez</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pharmacology, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27139613</idno><idno type="pmc">4855060</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855060</idno><idno type="RBID">PMC:4855060</idno><idno type="doi">10.3343/alm.2016.36.4.375</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000016</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hemoglobin Camperdown [β104Arg→Ser] Detection During Hemoglobin A<sub>1c</sub> Measurement via Capillary Electrophoresis</title><author><name sortKey="Brunel, Valery" sort="Brunel, Valery" uniqKey="Brunel V" first="Valéry" last="Brunel">Valéry Brunel</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Caneiro, Patrick" sort="Caneiro, Patrick" uniqKey="Caneiro P" first="Patrick" last="Caneiro">Patrick Caneiro</name><affiliation><nlm:aff id="A2">Department of Medical Biochemistry, General Hospital-Jacques Monod, Le Havre, France.</nlm:aff></affiliation></author><author><name sortKey="Lahary, Agnes" sort="Lahary, Agnes" uniqKey="Lahary A" first="Agnès" last="Lahary">Agnès Lahary</name><affiliation><nlm:aff id="A3">Department of Hematology, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Hue, Guy" sort="Hue, Guy" uniqKey="Hue G" first="Guy" last="Hue">Guy Hue</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Thuillez, Christian" sort="Thuillez, Christian" uniqKey="Thuillez C" first="Christian" last="Thuillez">Christian Thuillez</name><affiliation><nlm:aff id="A1">Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pharmacology, Rouen University Hospital, Rouen, France.</nlm:aff></affiliation></author></analytic><series><title level="j">Annals of Laboratory Medicine</title><idno type="ISSN">2234-3806</idno><idno type="eISSN">2234-3814</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jaisson, S" uniqKey="Jaisson S">S Jaisson</name></author><author><name sortKey="Leroy, N" uniqKey="Leroy N">N Leroy</name></author><author><name sortKey="Meurice, J" uniqKey="Meurice J">J Meurice</name></author><author><name sortKey="Guillard, E" uniqKey="Guillard E">E Guillard</name></author><author><name sortKey="Gillery, P" uniqKey="Gillery P">P Gillery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weykamp, C" uniqKey="Weykamp C">C Weykamp</name></author><author><name sortKey="Kemna, E" uniqKey="Kemna E">E Kemna</name></author><author><name sortKey="Leppink, S" uniqKey="Leppink S">S Leppink</name></author><author><name sortKey="Siebelder, C" uniqKey="Siebelder C">C Siebelder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ji, L" uniqKey="Ji L">L Ji</name></author><author><name sortKey="Yu, J" uniqKey="Yu J">J Yu</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Xia, Y" uniqKey="Xia Y">Y Xia</name></author><author><name sortKey="Xu, A" uniqKey="Xu A">A Xu</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilkinson, T" uniqKey="Wilkinson T">T Wilkinson</name></author><author><name sortKey="Gough, P" uniqKey="Gough P">P Gough</name></author><author><name sortKey="Owen, Mc" uniqKey="Owen M">MC Owen</name></author><author><name sortKey="Carrell, Rw" uniqKey="Carrell R">RW Carrell</name></author><author><name sortKey="Kronenberg, H" uniqKey="Kronenberg H">H Kronenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaborit, B" uniqKey="Gaborit B">B Gaborit</name></author><author><name sortKey="Nicolay, A" uniqKey="Nicolay A">A Nicolay</name></author><author><name sortKey="Valero, R" uniqKey="Valero R">R Valéro</name></author><author><name sortKey="Begu, A" uniqKey="Begu A">A Bégu</name></author><author><name sortKey="Badens, C" uniqKey="Badens C">C Badens</name></author><author><name sortKey="Bellanne Chantelot, C" uniqKey="Bellanne Chantelot C">C Bellanné-Chantelot</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="brief-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Lab Med</journal-id><journal-id journal-id-type="iso-abbrev">Ann Lab Med</journal-id><journal-id journal-id-type="publisher-id">ALM</journal-id><journal-title-group><journal-title>Annals of Laboratory Medicine</journal-title></journal-title-group><issn pub-type="ppub">2234-3806</issn><issn pub-type="epub">2234-3814</issn><publisher><publisher-name>The Korean Society for Laboratory Medicine</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27139613</article-id><article-id pub-id-type="pmc">4855060</article-id><article-id pub-id-type="doi">10.3343/alm.2016.36.4.375</article-id><article-categories><subj-group subj-group-type="heading"><subject>Letter to the Editor</subject><subj-group subj-group-type="subheading"><subject>Diagnostic Hematology</subject></subj-group></subj-group></article-categories><title-group><article-title>Hemoglobin Camperdown [β104Arg→Ser] Detection During Hemoglobin A<sub>1c</sub> Measurement via Capillary Electrophoresis</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Brunel</surname><given-names>Valéry</given-names></name><degrees>Pharm.D.</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Caneiro</surname><given-names>Patrick</given-names></name><degrees>Pharm.D.</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lahary</surname><given-names>Agnès</given-names></name><degrees>M.D.</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hue</surname><given-names>Guy</given-names></name><degrees>Pharm.D.</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Thuillez</surname><given-names>Christian</given-names></name><degrees>M.D.</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.</aff><aff id="A2"><label>2</label>Department of Medical Biochemistry, General Hospital-Jacques Monod, Le Havre, France.</aff><aff id="A3"><label>3</label>Department of Hematology, Rouen University Hospital, Rouen, France.</aff><aff id="A4"><label>4</label>Department of Pharmacology, Rouen University Hospital, Rouen, France.</aff><author-notes><corresp>Corresponding author: Valéry Brunel. Department of Medical Biochemistry, Rouen University Hospital, 1 rue de Germont Institut de Biologie clinique Rouen 76031, France. Tel: +33-232-88-14-41, Fax: +33-232-88-87-80, <email>valery.brunel@chu-rouen.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>7</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>25</day><month>4</month><year>2016</year></pub-date><volume>36</volume><issue>4</issue><fpage>375</fpage><lpage>376</lpage><history><date date-type="received"><day>09</day><month>11</month><year>2015</year></date><date date-type="rev-recd"><day>18</day><month>1</month><year>2016</year></date><date date-type="accepted"><day>02</day><month>3</month><year>2016</year></date></history><permissions><copyright-statement>© The Korean Society for Laboratory Medicine.</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions></article-meta></front><body><p>Dear Editor,</p><p>Reports on the analytical evaluation of capillary electrophoresis (CE) for glycated hemoglobin (HbA<sub>1c</sub>) measurement have already been published [<xref rid="B1" ref-type="bibr">1</xref>]. There have been several recent reports concerning the impact of the presence of hemoglobin variants on HbA<sub>1c</sub> measurement with the CE method. One study focused on the analytical interference of some hemoglobin variants [<xref rid="B2" ref-type="bibr">2</xref>], demonstrating that hemoglobin variants S, C, D, and E do not interfere either with HbA<sub>1c</sub> measurement or the glycation rate of hemoglobin variants, which is equal to the glycation rate of HbA. In a second report, analytical evaluation of CE showed that hemoglobin variant E and β-thalassemia do not affect HbA<sub>1c</sub> results. Moreover, most hemoglobin variants common to China can be detected by using a CE analyzer, and HbA<sub>1c</sub> values do not seem to be affected [<xref rid="B3" ref-type="bibr">3</xref>]. We report a case of hemoglobin Camperdown (HbCa) detected by using a Capillarys 2 Flex Piercing instrument (C2FP, Sebia, Lisses, France) during HbA<sub>1c</sub> measurement.</p><p>A 76-yr-old man receiving follow-up care for type 2 insulin-dependent diabetes was admitted to our hospital for a necrotic wound on the heel. To manage the diabetes, HbA1c was measured on a C2FP instrument in our clinical biology laboratory at Rouen University Hospital, France. The CE software flagged an alarm stating "<italic>Atypical profile</italic>" with an HbA<sub>1c</sub> value of 4.2% (22 mmol/mol). We observed an abnormality on the electropherogram (<xref ref-type="fig" rid="F1">Fig. 1</xref>), with a peak of unknown hemoglobin quantified at 3.0% and named fraction 1 by the CE software. There was no other abnormality on the electropherogram. The sample was also tested with a Bio-Rad Variant II analyzer (Bio-Rad, Marnes-la-Coquette, France) in the clinical biology laboratory at Le Havre General Hospital, France, which measured the HbA<sub>1c</sub> value at 52.2% (547 mmol/mol) because of migration of a probable hemoglobin variant in the HbA<sub>1c</sub> zone. Concentration of fructosamine (261 µmol/L; 205-260 µmol/L) was just above the reference values, which was not consistent with the two HbA<sub>1c</sub> values obtained. The patient's last HbA<sub>1c</sub> measurement was performed in our laboratory 10 yr previously. At that time, we observed a peak of unknown hemoglobin on HPLC (Variant, Bio-Rad), and we were not able to quantify HbA<sub>1c</sub>. The unknown hemoglobin was identified in the National Hemoglobinopathy Reference Laboratory (Créteil, France) as HbCa [β104Arg→Ser]. Ten years ago, the percentage of HbCa was estimated at 51.5%, which was consistent with a heterozygote patient. We supposed that the unknown fraction 1 on the electropherogram was the glycated fraction of HbCa. We observed that both glycated fractions were clearly separate, unlike HbCa and HbA<sub>0</sub>, which exactly coeluate, explaining the abnormal value of HbA<sub>1c</sub> calculated by the CE software. A manual off-line recalculation of the global glycated fractions percentage was performed, by integrating the sum of both peaks instead of HbA<sub>1c</sub> with the formula for percentage of glycated fractions=(HbA<sub>1c</sub>+HbCa<sub>1c</sub>)/(Total HbA<sub>0</sub> peak)×100. We then applied the calibration equation of the software, thereby obtaining a value of 6.3% (45 mmol/mol) for global glycated fractions.</p><p>HbCa is a rare variant, first described in 1974 [<xref rid="B4" ref-type="bibr">4</xref>], which is not associated with hematological abnormalities. Hemoglobin variants can affect the accuracy of HbA<sub>1c</sub> measurement, resulting in interference. This interference depends on the type of hemoglobin variant and the method used. Recently, Gaborit et al. [<xref rid="B5" ref-type="bibr">5</xref>] published the effects of this variant on HbA<sub>1c</sub> measurement using HPLC and immunoassay methods. They concluded that it was not possible to measure the exact HbA<sub>1c</sub> value with the affinity chromatography method. Moreover, immunoassay methods are blind to detecting such variants and probably underestimate HbA<sub>1c</sub> values. Herein we describe for the first time a case of HbCa interfering with CE HbA<sub>1c</sub> measurement. The C2FP HbA<sub>1c</sub> method is not able to differentiate HbA<sub>0</sub> from HbCa. The presence of an unknown peak must alert the pathologist. The CE software value is affected by negative bias due to the co-elution of HbCa and HbA<sub>0</sub>. Manual recalculation seems to yield good results for global glycated fractions, consistent with fructosamine. However, the threshold for HbA<sub>1c</sub> values must be applied with great care. In fact, the glycated rate of this rare variant has not yet been validated by any publication in the literature. Fructosamine, glycated albumin, or daily capillary blood glucose remain good markers to manage such patients.</p></body><back><ack><title>Acknowledgments</title><p>The authors are grateful to Nikki Sabourin-Gibbs, Rouen University Hospital, for her help in editing the manuscript.</p></ack><fn-group><fn fn-type="conflict"><p><bold>Authors' Disclosures of Potential Conflicts of Interest:</bold> No potential conflicts of interest relevant to this article were reported.</p></fn></fn-group><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jaisson</surname><given-names>S</given-names></name><name><surname>Leroy</surname><given-names>N</given-names></name><name><surname>Meurice</surname><given-names>J</given-names></name><name><surname>Guillard</surname><given-names>E</given-names></name><name><surname>Gillery</surname><given-names>P</given-names></name></person-group><article-title>First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA<sub>1c</sub> assay by capillary electrophoresis</article-title><source>Clin Chem Lab Med</source><year>2012</year><volume>50</volume><fpage>1769</fpage><lpage>1775</lpage><pub-id pub-id-type="pmid">23089707</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weykamp</surname><given-names>C</given-names></name><name><surname>Kemna</surname><given-names>E</given-names></name><name><surname>Leppink</surname><given-names>S</given-names></name><name><surname>Siebelder</surname><given-names>C</given-names></name></person-group><article-title>Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis</article-title><source>Clin Chem Lab Med</source><year>2015</year><volume>53</volume><fpage>e207</fpage><lpage>e210</lpage><pub-id pub-id-type="pmid">25719326</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ji</surname><given-names>L</given-names></name><name><surname>Yu</surname><given-names>J</given-names></name><name><surname>Zhou</surname><given-names>Y</given-names></name><name><surname>Xia</surname><given-names>Y</given-names></name><name><surname>Xu</surname><given-names>A</given-names></name><name><surname>Li</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants</article-title><source>Clin Chem Lab Med</source><year>2015</year><volume>53</volume><fpage>1451</fpage><lpage>1458</lpage><pub-id pub-id-type="pmid">25720069</pub-id></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilkinson</surname><given-names>T</given-names></name><name><surname>Gough</surname><given-names>P</given-names></name><name><surname>Owen</surname><given-names>MC</given-names></name><name><surname>Carrell</surname><given-names>RW</given-names></name><name><surname>Kronenberg</surname><given-names>H</given-names></name></person-group><article-title>Detection of variants of haemoglobin D in Australia: haemoglobin D Camperdown alpha 2 A beta 2 121 Glu leads to Val and haemoglobin D Punjab alpha 2 A beta 2 121 Glu leads to Gin</article-title><source>Med J Aust</source><year>1974</year><volume>26</volume><fpage>636</fpage><lpage>637</lpage><pub-id pub-id-type="pmid">4444612</pub-id></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gaborit</surname><given-names>B</given-names></name><name><surname>Nicolay</surname><given-names>A</given-names></name><name><surname>Valéro</surname><given-names>R</given-names></name><name><surname>Bégu</surname><given-names>A</given-names></name><name><surname>Badens</surname><given-names>C</given-names></name><name><surname>Bellanné-Chantelot</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Comparison of performances of various HbA1c methods in Haemoglobin Camperdown variant detection: consequences in diabetes management</article-title><source>Clin Chim Acta</source><year>2009</year><volume>403</volume><fpage>262</fpage><lpage>263</lpage><pub-id pub-id-type="pmid">19168040</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Fig. 1</label><caption><title>Abnormal electropherogram obtained by Capillarys 2 Flex Piercing instrument. Abnormal electropherogram with software alarm "atypical profile" showing a peak of unknown hemoglobin (HbCa<sub>1c</sub>), which is the glycated form of hemoglobin Camperdown (HbCa). HbCa is not visible owing to co-eluation with HbA<sub>0</sub>.</title></caption><graphic xlink:href="alm-36-375-g001"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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