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Unusual finding of high oxygen affinity haemoglobinopathy treated with phlebotomy: A rare but predictable union

Published:October 09, 2021DOI:https://doi.org/10.1016/j.transci.2021.103290
      Dear Sir,
      Haemoglobinopathies are monogenic disorders in the genes that encode globin chains that can lead to a defective globin production or a variant in the haemoglobin structure. Congenital erythrocytosis is a clinical manifestation that can be found in patients with structural haemoglobin variants with a high oxygen affinity [
      • Kalotychou V.
      • Tzanetea R.
      • Konstantopoulos K.
      • Papassotiriou I.
      • Rombos I.
      Erythrocytosis due to a combination of the high oxygen affinity hemoglobin variant, Hb Olympia [beta20(B2)Val--&Met] with beta- and alpha-thalassemia mutations: first case in the literature.
      ,
      • Bard H.
      • Peri K.G.
      • Gagnon C.
      The biologic implications of a rare hemoglobin mutant that decreases oxygen affinity.
      ]. We report two different high oxigen affinity haemogobinopathies found during a haematologic counselling that needed phlebotomy treatments to reduce haematocrit value [
      • Assi T.B.
      • Baz E.
      Current applications of therapeutic phlebotomy.
      ]. The rarity of these hemoglobinopaties in our country proved that a high-performance liquid chromotography (HPLC) analysis should be required in the diagnostic tests of patients with high haematocrit level in absence of other secondary conditions of polyglobulia [
      • Orvain C.
      • Joly P.
      • Pissard S.
      • Badiou S.
      • Badens C.
      • Bonello-Palot N.
      • et al.
      Diagnostic approach to hemoglobins with high oxygen affinity: experience from France and Belgium and review of the literature.
      ].
      A 68 years old patient born in Italy was treated for a polyglobulia with irregular phlebotomies per year without a significative reduction of the haematocrit level. A policitemia vera was excluded, however the familiar anamnesis revealed that the mother was affected by an erythrocyte plethora that was never investigated. The HPLC chromatogram showed an abnormal peak in the P3 area of a 39.7 %, HbA 48.8 %, HbA2 2.6 % and HbF less 0.8 % and a molecular biology study showed a mutation C > G at the nucleotide +469 (codon96) in a heterozygous state that was responsible for an amino acid substitution [ß 96 Leu > Val] characteristic of the variant Hb Regina.
      The second case refers to a pair of brothers aged 57 and 58 born in Italy; in the anamnesis they have a history of blood donor deferred for repeated values of high haematocrit level and a subsequently histories of phlebotomy. An HPLC analysis was performed and the chromatogram showed a haemoglobin variant represented by an abnormal peak in the P5 area of a 39.2 %, HbA2 2.3 %, HbF <1.0 % and the molecular biology study showed a mutation T > A at the nucleotide 112 (codon 20), in a heterozygous state that was responsible for an amino acid substitution [ß 20 Val > Glu] characteristic of the variant Hb Trollhattan.
      Both the patients were included in a programme of regular phlebotomy to reach and maintain an hematocrit value of 50–52 %.
      Hb Regina and the Hb Trollhattan, were described the first time in a Scandinavian family and in a Swedish one, respectively. They are characterized by a compensatory erythrocytosis of genetic origin related to high oxigen affinity [
      • Wajcman H.
      • Galactéros F.
      Hemoglobins with high oxygen affinity leading to erythrocytosis. New variants and new concepts.
      ,
      • Percy M.J.
      • Butt N.N.
      • Crotty G.M.
      • Drummond M.W.
      • Harrison C.
      • Jones G.L.
      • et al.
      Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis.
      ]. In these patients the reduction to 52 % of the haematocrit remains the main target; only in the case of comorbidity for thrombotic risk it is suggested to maintain the haematocrit value less than 50 % [
      • Mangin O.
      High oxygen affinity hemoglobins.
      ].
      A legitimate question is if people with high haematocrit level and carrying a hemoglobin variant with a high oxygen affinity with congenital erythrocytosis are suitable for blood donation as haemocromatosis. We think it is unlilkely because they will not be able to maintain a good therapeutic haematocrit range with quarterly donations and it is strongly possible that transfusion of erythrocytes with high oxygen affinity haemoglobin would not have any clinical benefit.
      These cases highlight the importance to introduce a HPLC analysis for haemoglobin in patients with high haematocrit level and/or poliglobulia to exclude congenital erythrocytosis from high oxigen affinity haemogobinopathies. In the last period the global migration leds to a continued spread of these anomalies to all the region of the world as showed by the description in Italy of Hb Regina and the Hb Trollhattan coming from the Nordic countries.

      Declaration of Competing Interest

      The authors report no declarations of interest.

      Acknowledgments

      E.T. evaluated the patient, analyzed the HPLC data, reviewed the literature and wrote the manuscript; A.M and P.V were involved in the patient’s clinical management and treatment; L.G and V. B performed HPLC test in the laboratory; AB revised the paper and approved the final version.

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