{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:16:31Z","timestamp":1789604191965,"version":"build-2803163510"},"reference-count":13,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>High oxygen affinity hemoglobin (HOAH) is the main cause of constitutional erythrocytosis. Mutations in the genes coding the alpha and beta globin chains (HBA1, HBA2 and HBB) strengthen the binding of oxygen to hemoglobin (Hb), bringing about tissue hypoxia and a secondary erythrocytosis. The diagnosis of HOAH is based upon the identification of a mutation in HBA1, HBA2 or HBB in specialized laboratories. Phenotypic studies of Hb are also useful, but electrophoretic analysis can be normal in 1\/3 of cases. The establishment of the dissociation curve of Hb can be used as another screening test, a shift to the left indicating an increased affinity for Hb. The direct measurement of venous P50 using a Hemox Analyzer is of great importance, but due to specific analytic conditions, it is only available in a few specialized laboratories. Alternatively, an estimated measurement of the P50 can be obtained in most of the blood gas analyzers on venous blood. The aim of our study was therefore to determine whether a normal venous P50 value could rule out HOAH. We sequenced the HBB, HBA1 and HBA2 genes of 75 patients with idiopathic erythrocytosis. Patients had previously undergone an exhaustive medical check-up after which the venous P50 value was defined as normal. Surprisingly, sequencing detected HOAH in three patients (Hb Olympia in two patients, and Hb St Nazaire in another). A careful retrospective examination of their medical files revealed that (i) one of the P50 samples was arterial; (ii) there was some air in another sample; and (iii) the P50 measurement was not actually done in one of the patients. Our study shows that in real life conditions, due to pre-analytical contingencies, a venous P50 value that is classified as being normal may not be sufficient to rule out a diagnosis of HOAH. Therefore, we recommend the systematic sequencing of the HBB, HBA1 and HBA2 genes in the exploration of idiopathic erythrocytosis.<\/jats:p>","DOI":"10.3390\/genes13010132","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T23:17:07Z","timestamp":1642029427000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Importance of Sequencing HBA1, HBA2 and HBB Genes to Confirm the Diagnosis of High Oxygen Affinity Hemoglobin"],"prefix":"10.3390","volume":"13","author":[{"given":"Mathilde","family":"Filser","sequence":"first","affiliation":[{"name":"Biology Division, Department of Biological Hematology, Dijon Hospital, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Gardie","sequence":"additional","affiliation":[{"name":"Thorax Institute, Nantes Hospital, CNRS, Inserm, Nantes University, 44000 Nantes, France"},{"name":"Ecole Pratique des Hautes Etudes, EPHE, Science and Letters Paris University, 75014 Paris, France"},{"name":"Laboratory of Excellence GR-Ex, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Wemeau","sequence":"additional","affiliation":[{"name":"Blood Disease Department, Claude Huriez Hospital, Lille Hospital, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Aguilar-Martinez","sequence":"additional","affiliation":[{"name":"Department of Biological Hematology, Saint Eloi Hospital, Montpellier Hospital & Montpellier University, 34000 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-6177","authenticated-orcid":false,"given":"Muriel","family":"Giansily-Blaizot","sequence":"additional","affiliation":[{"name":"Department of Biological Hematology, Saint Eloi Hospital, Montpellier Hospital & Montpellier University, 34000 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Girodon","sequence":"additional","affiliation":[{"name":"Biology Division, Department of Biological Hematology, Dijon Hospital, 21000 Dijon, France"},{"name":"Laboratory of Excellence GR-Ex, 75015 Paris, France"},{"name":"Inserm U1231, Bourgogne University, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-018-0054-y","article-title":"The 2016 WHO Classification and Diagnostic Criteria for Myeloproliferative Neo-Plasms: Document Summary and In-Depth Discussion","volume":"8","author":"Barbui","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1182\/asheducation-2009.1.629","article-title":"Idiopathic Erythrocytosis: A Disappearing Entity","volume":"1","author":"McMullin","year":"2009","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/humu.22448","article-title":"Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases","volume":"35","author":"Bento","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1002\/ajh.25150","article-title":"Genotype-Phenotype Correlation of Hereditary Erythrocytosis Mutations. A Single Center Experience","volume":"93","author":"Oliveira","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.3324\/haematol.2016.158337","article-title":"Gene Panel Sequencing in Idiopathic Erythrocytosis","volume":"102","author":"Girodon","year":"2017","journal-title":"Haematol."},{"key":"ref_6","first-page":"39","article-title":"Diagnostic Approach to Hemoglobins with High Oxygen Affinity: Experience from France and Belgium and Review of the Literature","volume":"75","author":"Orvain","year":"2017","journal-title":"Ann. Biol. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1081\/HEM-58571","article-title":"Hemoglobins with High Oxygen Affinity Leading to Erythrocytosis. New Variants and New Concepts","volume":"29","author":"Wajcman","year":"2005","journal-title":"Hemoglobin"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1016\/j.revmed.2009.03.115","article-title":"Polyglobulies: Penser \u00e0 Rechercher Une H\u00e9moglobine Hyperaffine Pour L\u2019oxyg\u00e8ne","volume":"30","author":"Esparcieux","year":"2009","journal-title":"Rev. M\u00e9d. Interne"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1365-2796.2008.02014.x","article-title":"Blood P50 Evaluation Enhances Diagnostic Definition of Isolated Erythrocytosis","volume":"265","author":"Rumi","year":"2009","journal-title":"J. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00277-012-1667-z","article-title":"Does Venous Blood Gas Analysis Provide Accurate Estimates of Hemoglobin Oxygen Affinity?","volume":"92","author":"Huber","year":"2013","journal-title":"Ann. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"987","DOI":"10.2170\/jjphysiol.33.987","article-title":"A Simple Microtonometric Method for Whole Blood Oxygen Dissociation Curve and A Critical Evaluation of the \u201cSingle Point\u201d Procedure for Blood P50","volume":"33","author":"Kohzuki","year":"1983","journal-title":"Jpn. J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1182\/blood.2020008424","article-title":"Increased Incidence of Germline PIEZO1 Mutations in Individuals with Idio-Pathic Erythrocytosis","volume":"137","author":"Filser","year":"2021","journal-title":"Blood"},{"key":"ref_13","first-page":"399","article-title":"International Federation of Clinical Chemistry (IFCC)3, Committee on pH, Blood Gases and Electrolytes: Approved IFCC Recommendation on Defini-Tions of Quantities and Conventions Related to Blood Gases and pH","volume":"33","author":"Burnett","year":"1995","journal-title":"Eur. J. Clin. Chem. Clin. Biochem."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:02:11Z","timestamp":1760364131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,12]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["genes13010132"],"URL":"https:\/\/doi.org\/10.3390\/genes13010132","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,12]]}}}