HbA2 : biology, clinical relevance and a possible target for ameliorating sickle cell disease

Br J Haematol. 2015 Sep;170(6):781-7. doi: 10.1111/bjh.13570. Epub 2015 Jun 24.


HbA2 , a tetramer of α- and δ-globin chains, provides a diagnostic clue to the presence of β-thalassaemia trait. This minor haemoglobin, which forms about 2-3% of the total, has no known physiological role, but has the interesting property of preventing polymerization of deoxy-sickle haemoglobin. If it were possible to increase the level of HbA2 sufficiently it could have a benefit in sickle cell disease similar to that of foetal haemoglobin. Moreover, HbA2 is present in all erythrocytes, an advantage not found with foetal haemoglobin, which is heterocellularly expressed. The molecular basis of HbA2 gene (HBD) expression is partially understood, and with new molecular tools, it might be possible to induce levels of HbA2 that could be clinically important. However, high concentrations of this positively charged haemoglobin might damage the erythrocyte membrane; also, the reciprocal relationship of δ- and γ-globin gene (HBD and HBG1/2, respectively) expression might negate any benefit of increasing transcription of the former.

Keywords: HbS polymer; delta-globin gene; foetal haemoglobin; haemoglobin switching; sickle haemoglobin.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anemia, Sickle Cell / drug therapy
  • Anemia, Sickle Cell / etiology*
  • Animals
  • Evolution, Molecular
  • Hemoglobin A2 / chemistry
  • Hemoglobin A2 / physiology*
  • Humans
  • Protein Biosynthesis


  • Hemoglobin A2