title: Diagnostic approach to hemoglobins with high oxygen affinity: experience from France and Belgium and review of the literature.
abstract: Congenital causes of erythrocytosis are now more easily identified due to the improvement of the molecular characterization of many of them. Among these causes, hemoglobins with high oxygen affinity take a large place. The aim of this work was to reevaluate the diagnostic approach of these disorders. To assess the current practices, we sent a questionnaire to the expert laboratories in the diagnosis of hemoglobinopathies in France and Belgium. In parallel, we gathered the methods used for the diagnosis of the hemoglobins with high oxygen affinity indexed in the international database HbVar. Even though they remain a rare cause of erythrocytosis (1 to 5 positive diagnosis every year in each of the questioned specialized laboratories), hemoglobins with high oxygen affinity are increasingly suspected by clinicians. Phenotypic assessment by laboratory techniques remains a main step in their diagnosis as it enables the finding of 93% of them in the questioned laboratories (28 of the 30 variants diagnosed during the last 5 years). Among the 96 hemoglobin variants with high oxygen affinity indexed in the international database, 87% could be diagnosed with phenotypic techniques. A direct measure of the p50 with the Hemox-Analyzer is included in the diagnostic approach of half of the laboratories only, because of the poor availability of this apparatus. Comparatively, the estimation of p50 by blood gas analyzers on venous blood is a much more convenient and attractive method but due to the lack of proof as to its effectiveness in the diagnosis of hemoglobins with high oxygen affinity, it requires further investigations. Beta- and alphaglobin genes analysis by molecular biology techniques is essential as it either allows a quick and definite identification of the variant or definitely excludes the diagnosis. It is thus systematically performed as a first or second step method, according to the laboratory practice.
authors.affiliation: Laboratoire d'hématologie, Hôpital Saint Éloi, CHU de Montpellier, Montpellier, France, Service des maladies du sang, CHU d'Angers, Angers, France.
authors.forename: Corentin
authors.initials: C
authors.lastname: Orvain
authors.affiliation: Laboratoire CRIS EA647, Équipe "Biologie vasculaire et du globule rouge", Université de Lyon, Lyon, France, Labex GR-Ex, Paris, France - Institut Universitaire de France, Unité de pathologie moléculaire du globule rouge, Fédération de biochimie et de biologie spécialisée, Hôpital Édouard Herriot, Hospices civils & Université Claude Bernard-Lyon 1, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.affiliation: Département de génétique moléculaire, Hôpital Mondor, AP-HP, Créteil, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.affiliation: Laboratoire de biochimie, Hôpital Lapeyronie, CHU de Montpellier, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Badiou
authors.affiliation: Laboratoire de génétique moléculaire, Centre de référence maladies rares Thalassémies, Hôpital de la Timone, AP-HM, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: Laboratoire de génétique moléculaire, Centre de référence maladies rares Thalassémies, Hôpital de la Timone, AP-HM, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonello-Palot
authors.affiliation: Laboratoire de génétique moléculaire, Hôpital Robert Debré, AP-HP, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Couque
authors.affiliation: Département de chimie médicale, Hôpital Erasme, Bruxelles, Belgique.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gulbis
authors.affiliation: Laboratoire d'hématologie, Hôpital Saint Éloi, CHU de Montpellier, Montpellier, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Martinez
mesh_terms: D001530:Belgium; D001784:Blood Gas Analysis / Q000379:methods / Q000592:standards; D003937:Diagnosis, Differential; D005602:France; D005838:Genotype; D006453:Hemoglobinopathies / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000032:analysis*; D006801:Humans; D010100:Oxygen / Q000032:analysis / Q000378:metabolism; D010641:Phenotype; D011086:Polycythemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics
chemical_list: D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D010100:Oxygen
keywords: erythrocytosis; hemoglobin with high oxygen affinity; p50