Diagnóstico diferencial de las eritrocitosis. Hemoglobinas con alta afinidad por el oxígeno

  1. Ana Villegas Martínez 1
  2. Ataulfo González Fernández 2
  3. Paloma Ropero 2
  4. Jorge Martínez Nieto 2
  5. Nahir Moreno 2
  6. Blanca Colás 2
  7. Alberto López 2
  8. Celina Benavente 2
  1. 1 Real Academia Nacional de Medicina de España – Hematología Servicio de Hematología. Hospital Clínico San Carlos.
  2. 2 Servicio de Hematología. Hospital Clínico San Carlos.
Zeitschrift:
Anales de la Real Academia Nacional de Medicina

ISSN: 0034-0634

Datum der Publikation: 2020

Nummer: 137

Seiten: 35-43

Art: Artikel

DOI: 10.32440/AR.2020.137.01.REV04 DIALNET GOOGLE SCHOLAR lock_openOpen Access editor

Andere Publikationen in: Anales de la Real Academia Nacional de Medicina

Zusammenfassung

Erythrocytosis is defined as the increase in red cell mass above 25% of its normal value. This increase have a parallel increase of hematocrit level. It was known that in situations of tissue hypoxia erythropoietin was the largest ensurer for erythrocyte synthesis, but it was not known how cells detected these changes and contributed to oxygen availability. The research on oxygen changes of Gregg Semenza, Willian Kaelin and Peter Radcliffe have earned them the 2019 Nobel Price in Physiology and Medicine. They describe how regulations is carried out at the cellular level by identifying 3 proteins, the hypoxia-inductible factor (HIF), prolyl hidrolase domain (PHD) and tumor suppressor factor, Von Hippel-Lindau (VHL).These authors analyze the mechanism of oxygen homeostasis in situations under well-oxygenated conditions and in situations of hypoxia and therefore as erythropoietin synthesis is performed through the hypoxia-responder element (HRE) located in region promoter of the EPO gene in peritubular renal interstitial cells. Erythrocytosis can be classified either as primary or secondary and can be either congenital and acquired. Subsequently the differential diagnosis is established between the subtypes of erythrocytosis, initiating the description with the diagnostic criteria of plycythemia vera. The diagnostic test needed to perform their differentiation are evaluated along with the applicable flow chart to schedule the study of erythrocytosis. Finally we expose our experience in hemoglobinopathies with high affinity for oxygen studied at the Clinico San Carlos Hospital, belonging to 34 patients from 18 families with 11 different variants of hemoglobinophaties. Two of them have only been described in our country. Despite having high hematocrit and hemoglobin levels and in two of then associated with thalassemia and presenting null values of normal hemoglobin A, patients are asmptomatic

Bibliographische Referenzen

  • Arrizabalaga Amuchastegui B. Eritrocitosis secundarias adquiridas. Eritrocitosis idiopática. En “Eritropatología”. Coordinadores: Beatriz Arrizabalaga, F. Ataulfo González, Ángel Remacha. Barcelona. Ambos Mark. 2017; pág 501-513.
  • Spivak JL. Myeloproliferative neoplasms. N Engl J Med 2017; 376(22): 2168-2181.
  • Patnaik MM, Tefferi A. The complete evaluation of erythrocytosis: congenital and acquired. Leukemia 2009; 23: 834-844.
  • Guillermo Martín Núñez. Eritrocitosis, diagnóstico diferencial y tratamiento. LXI Congreso Nacional SEHH. Congreso Nacional SETH. Programa educacional 2019; pág: 7-15.
  • Wang GL, Semenza GL. Molecular basis of hipoxia-induced erythropoietin expresión. Curr Op. Hematol 1996; 3(2): 156-162.
  • Kuhrt D, Wojchowski DM. Emerging EPO and EPO receptor regulators and signal transducers. Blood 2015; 125: 3536-3541.
  • Mc Mullin MF. Congenital erythrocytoses. Int J Lab Hematol 2016; 38(1): 59-65.
  • Maia TM, Bento C, Ribeiro LM. Eritropoyesis en “Eritropatología”. Coordinadores: Beatriz Arrizabalaga, F. Ataulfo González, Ángel Remacha. Barcelona. Ambos Mark 2017; pág 3-16.
  • Koulnis M, Porpiglia E, Hidalgo D, Socolovsky M. Erythropoieis from molecular pathways to system properties. Adv Exp Med Biol 2014; 844: 37-58.
  • Semenza GL. Hypoxia-inducible factors in Physiology and Medicine. Cell 2012; 148(3): 399-408. Doi 10.1016/j cds. 2012.01.021
  • Kaelin WG, Ratcliffe PJ. Oxygen sensing by metazoans the central role of the HIF dydroxylase pathway. Mol Cell 2008; 30: 393-402.
  • Jiang BH, Rue E, Wang GL, Rose R, Semenza GL. Dimerization, DNA binding and transactivation propieties of hipoxia-inductible factor 1. J Biol Chem 1996; 271: 17771-17778
  • Percy MJ, Zhan Q, Flores A et al. A family with erythrocytosis establishes a role for prolyl hydroxglase domain protein 2 in oxygen homeostasis. Proc Natl Acad Sci USA 2006; 103: 654-659.
  • Franke K, Gassmann M, Wieloclx B. Erythrocytosis: The HIF patway in control. Blood 2013; 122(7): 1122-1128.
  • Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE. Hypoxia-inductible nuclear factors bind to an enhancer element locate 3’ to the human erythropoietin gene. Proc Natl Acad Sci USA 1991; 88: 5680-5684.
  • Semenza GL. Defining the role of hipoxia-inductible factor 1 in cáncer biology and therapeutics. Oncogene 2010; 29: 625-634.
  • González Fernández FA, Villegas A, Ropero P et al. Haemoglobinopathies with high oxygen affinity. Esperience of Erythropathology Cooperative Spanish Group. Ann Hematol 2009; 88: 325-328.
  • Bento C, Percy MJ, Gardie B et al: On behalf of ECE-Consortium. Genetic basis of congenital erythrocytosis: mutation update on line databases Hum Mutat 2014; 35: 15-26.
  • Barbui T, Tefferi A, Vannuchi AM et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations fron European Leukemia Net. Leukemia 2018; 32(3): 1057-1069.
  • Lee FS, Percy MJ. The HIF pathway and erythrocytosis. Annu Rev Pathol 2011; 6: 165-192.
  • Cario H, Schwartz R, Jorch N. Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis. Haematologica 2005; 90(1): 19-24.
  • Cario H, McMullin F, Bento C et al. Erythrocytosis in children and adolescents: classification, characterization and consensus recommendations for the diagnostic approach. Pediatr. Blood Cáncer 2013; 60(11): 1734-1738.
  • Percy MJ, Furlow PW, Lucas GS et al. A gain of function mutation in the HIF2α gene in familial erythrocytosis. N Engl J Med 2008; 358(2): 162-168.
  • Charache S, Weatherall DJ, Clegg JB. Policythemia associated with a hemoglobinopathy. J Clin Invest 1966; 45: 813-822.
  • Solmac S, Kuksal F, Ganidagli S. Is obstructive sleep apnea syndrome really one of the causes of secundary polycythaemia. Hematology 2015; 20(2): 108-111.
  • Sykes DB, Schroyens W. Complete responses in the TEMPI Syndrome after treatment with Daratumumab. N Engl J Med 2018; 378(23): 2240-2242.
  • Lee G, Arcasoy MO. The clinical and laboratory evaluation of the patient with erythrocytosis. J Int Med 2015; 26: 297-302.
  • Torres W, García Roa M, Manubens A et al. Hemoglobinopathies with high oxygen affinity. Haematologica 2015; 99(51): 183.
  • Torres W, García Roa M, Gutiérrez Alvariño M et al. Characterization of 6 hemoglobinophaties ocurring with cianosis and/or lowering the oxygen saturation. Haematologica 2015; 99(51): 183.
  • Wajcman H, Galacteros F. Hemoglobin with high oxygen affinity leading to erythrocytosis. New variants and new concepts. Hemoglobin 2005; 29(2): 91-106.
  • Juncá J, Villegas A, Ropero P, Polo M, Valverde F. Characterization of a new hemoglobin variant: Hb Badalona β(31) Leu→val). Ann Hematol 2002; 81(4): 179-181.
  • Ropero P, Fernández Lago C, Villegas A et al. Hb La Coruña [β38 (C4) Thr→Ille] a new hemoglobin leading to familial polycythemia. Hemoglobin 2006; 30(3): 379-383.
  • Ropero P, González FA, Cela E et al. Erythrocytosis in a child due to Hb Andrew-Minneapolis [β 144 (HC1) Lys→ASN (AAG>AAT o AAC] associated with a Spanish (δβ)º thalassemia. Hemoglobin 2013; 37(1): 48-55.
  • Kaelin WG. Proline hydroxylation and gene expresión. Annu, Rev Biochem 2005; 74: 115-118.
Fuente de los datos: Dialnet