Clinical Information

A large number of variants of hemoglobin (Hb) have been recognized. Although many do not result in clinical or hematologic effects, clinical symptoms that can be associated with Hb disorders include microcytosis, sickling disorders, hemolysis, erythrocytosis/polycythemia, cyanosis/hypoxia, anemia (chronic, compensated, or episodic), and increased methemoglobin or sulfhemoglobin results (M-Hb).

For many common Hb variants (eg, Hb S, Hb C, Hb D, and Hb E, among many others), protein studies will be sufficient for definitive identification. However, some Hb conditions may be difficult to identify by protein methods alone and may require molecular methods for confirmation. Hb disorders commonly occur as compound disorders (2 or more genetic variants) that can have complex interactions and variable phenotypes. In these situations, molecular testing may be necessary for accurate classification. It is important to note that although powerful as an adjunct for a complete and accurate diagnosis, molecular methods without protein data can give incomplete and possibly misleading information due to limitations of the methods. Accurate classification of Hb disorders and interpretation of genetic data requires the incorporation of protein analysis results. This profile is well-suited for the classification of Hb disorders.

Mayo Clinic Laboratories receives specimens from a wide geographic area and nearly one-half of all specimens tested exhibit abnormalities. The most common abnormality is an increase in Hb A2 to about 4% to 8%, which indicates beta-thalassemia minor when present in the correct clinical context. A wide variety of other hemoglobinopathies are also frequently encountered. Ranked in order of relative frequency, these are: Hb S (sickle cell disease and trait), C, E, Lepore, G-Philadelphia, Hb H disease, D-Los Angeles, Koln, Constant Spring, O-Arab. Other variants associated with hemolysis, erythrocytosis/polycythemia, microcytosis, cyanosis/hypoxia are routinely identified; however, some will not be detected by routine screening methods and require communication of clinical findings to prompt indicated reflex testing options. Alpha-thalassemia genetic variants are very common in the United States, occurring in approximately 30% of African Americans and accounting for the frequent occurrence of microcytosis in persons of this ethnic group. Some alpha-thalassemia conditions (eg, Hb H, Barts) can be identified in the Hb electrophoresis protocol, although Hb Constant Spring may or may not be evident by protein methods alone dependent upon the percentage present. It is important to note, alpha-thalassemias that are from only 1 or 2 alpha-globin gene deletions are not recognized by protein studies alone and alpha gene deletion and duplication testing is required.