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.

Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, detected during the analysis of glycated haemoglobin (HbA1C) by high performance liquid chromatography

“…Over 700 abnormal haemoglobins have been described throughout the world. 14 One fifth of the haemoglobinopathies show symptoms such as cyanosis, 15 16 polycythaemia, 17 haemolysis and/or anaemia, [18][19][20] whereas the remaining four fifths are asymptomatic. Most of the cases are accompanied by changes in electric charge because of the substitution of amino acids, resulting in an abnormal HPLC elution pattern.…”

Sporadic case of hemoglobin Bushwick detected by chance in aplastic crisis

“…The following tests were performed by methods described previously 1,3 on the patient’s family members to screen for hemoglobinopathy: brilliant cresyl blue staining for RBC inclusion bodies, HbF and HbA 2 concentrations, heat precipitation, isopropanol precipitation test, T 1 2 of RBC glycerol lysis, isoelectric focusing and reverse‐phase high‐performance liquid chromatography(R‐HPLC).…”

“…Unstable hemoglobin (US‐Hb) is one of the well recognized causes of congenital non‐spherocytic hemolytic anemia, with over 90 molecular variants of it having been reported so far in the world. 1 The US‐Hb precipitates within red blood cells (RBC) as insoluble inclusions or Heinz bodies, because of an important abnormality in the primary structure of the globin chain. However, the clinical manifestations of US‐Hb are variable and range from chronic hemolytic anemia, which is nearly asymptomatic, to life‐threatening severe hemolysis.…”

What Do We Need beyond Hemoglobin A1c to Get the Complete Picture of Glycemia in People with Diabetes?

“…While some of these hemoglobin variants are clinically harmless, others can cause illness. These latter are divided into the following four well-defined groups 35:Variants with a tendency to aggregate and with sickle cell formation (e.g., the sickle cell hemoglobin HbS 36;Variants with abnormal hemoglobin synthesis (e.g., HbE) 37;Variants with a tendency to precipitate and with hemolysis (e.g., Hb Köln) 38;Variants with abnormal oxygen transport and congenital polycythemia (e.g., Hb Johnstown) 39.…”