Hemoglobins With High Oxygen Affinity Leading to Erythrocytosis. New Variants and New Concepts |
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Abstract: | This review brings some new insights on erythrocytosis of genetic origin related to problems of oxygen delivery by hemoglobin (Hb). A few molecular mechanisms are individualized among the about 100 Hb variants that cause compensatory erythrocytosis. The most frequently observed structural modifications are localized in the α1β2 interface, or at the C-terminal. They impair formation of a stable T state. Others mutations modify directly or indirectly the surrounding of the heme and the site where oxygen binds. A special interest is brought to the dose effect considering the possibility for formation of hybrid tetramers with altered oxygen binding properties. Homozygous cases, and patients who are compound heterozygotes for a high oxygen affinity Hb and a thalassemia (thal), are discussed. Several examples are provided, specially documented for Hb Olympia [β20(B2)Val→Met] and Hb Saint Nazaire [β103(G5)Phe→Ile]. Other mechanisms leading to erythrocytosis are discussed, and finally, an algorithm is proposed for etiological diagnosis. |
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Keywords: | Polycythemia Abnormal hemoglobin (Hb) High oxygen affinity 2,3-Diphosphoglycerate (2,3-DPG) Erythropoietin |
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