Unstable hemoglobins

Hemoglobin concentration is variable depending on the variant of unstable hemoglobin, ranging from normal values to severe anemia. In some cases, anemic levels may occur only during hemolytic phases caused or exacerbated by infections or certain medications. MCV may be increased, MCH and MCHC decreased. Reticulocytes show increased values in the presence of hemolysis. If unstable hemoglobin shows increased oxygen affinity, an increased red cell count is regularly observed.

The proportion of abnormal hemoglobin from unstable globin variants is variable and is undetectable in hemoglobin differentiation in >50% of cases. In unstable hemoglobins with unchanged electrophoretic mobility, the unstable hemoglobin migrates with physiological HbA and cannot be distinguished from it in electrophoresis. Detectable unstable hemoglobin variants range from 35-40% of total hemoglobin (e.g. Hb Hammersmith) to barely detectable amounts in particularly unstable variants, such as Hb Cagliari. The most common unstable hemoglobin, Hb Köln, usually accounts for 10 - 15% of total hemoglobin. HbF and HbA2 may be elevated.

Unstable hemoglobins may escape detection by hemoglobin differentiation due to their rapid degradation or HbA-identical electrophoretic mobility. Molecular genetic methods are therefore regularly used to confirm the presence of a variant in a globin gene that causes the formation of unstable hemoglobin. Since unstable hemoglobins are predominantly caused by single base variants, sequencing is of particular importance.