Unstable hemoglobins

Abstract

About 70 variants of Hb A with associated hemolytic disorders have been reported during the past 30 years. I have classified them according to four grades of severity of chronic hemolysis. Acute episodes of severe hemolysis may be seen in all classes. In addition, some 80 variants without overt hemolysis have given positive results with in vitro hemoglobin instability tests. The stereochemical bases for instability can be conjectured in most cases, although few unstable hemoglobins have actually been studied by X-ray crystallography. The mechanisms for denaturation of normal Hb A and its acceleration in unstable hemoglobins were proposed some 15 years ago. The alterations of membrane lipids and proteins leading to red cell senescence and the relevance of hemoglobin denaturation to this process are presently being investigated. Several "hyperunstable" variants are clinically silent, or equivalent to a thalassemia, probably because of very efficient degradation of the abnormal chains.