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The erythrocyte effects of haemoglobin O ARAB
Author(s) -
Nagel Ronald L.,
Krishnamoorthy Rajagopal,
Fattoum Slaheddine,
Elion Jacques,
Genard Nathalie,
Romero Jose,
Fabry Mary E.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01755.x
Subject(s) - medicine
To test the hypothesis that HbO ARAB induces an increase in red cell mean corpuscular haemoglobin concentration (MCHC), we studied members of four Tunisian families who were either homo‐ or heterozygous for HbO ARAB or were double heterozygotes for HbS and HbO ARAB . The α‐gene status was also tested. The findings included: (1) Distinctive variation in red cell density (MCHC) as determined by separation of red cells on isopycnic gradients: (a) All red cells from patients homozygous for HbO ARAB were denser than normal red cells, as is observed for homozygous HbC patients. (b) In patients heterozygous for HbO ARAB , red cell density was strongly influenced by the presence of α‐thalassaemia. The coexistence of −α/αα resulted in an average red cell density slightly greater than normal (AA) red cells. Patients heterozygous for HbO ARAB with a normal complement of four α genes had denser red cells similar to sickle cell disease with some cells of normal density but with most cells very dense. (c) Finally, the double heterozygotes for HbS and HbO ARAB had significant haemolytic anaemia and red cells denser than normal with some as dense as the densest cells found in sickle cell anaemia. (2) Reticulocytes in patients homozygous for HbO ARAB were found in the densest density fraction of whole blood. (3) Cation transport in patients homozygous for HbO ARAB was abnormal, with K:Cl cotransport activity similar to that of HbS‐Oman and only somewhat lower than in sickle cell anaemia red cells. The activity of the Gardos channel was indistinguishable from that found in HbS, HbC and HbS‐Oman cells. We conclude that the erythrocytic pathogenesis of HbO ARAB involves the dehydration of red cells due, at least in part, to the K:Cl cotransport system. The similarity of the charge and consequences of the presence of both HbC and HbO ARAB, which are the products of mutations at opposite ends of the β‐chain, raises the possibility that this pathology is the result of a charge‐dependent interaction of these haemoglobins with the red cell membrane and/or its cytoskeleton and that this abnormality is present early in red cell development.