The erythrocyte membrane plays a critical role in the maintenance of the biconcave shape and integrity of the red cell.
It provides flexibility, durability, and tensile strength, enabling erythrocytes to undergo extensive and repeated distortion during their passage through the microvasculature.
It consists of a lipid bilayer with embedded transmembrane proteins and an underlying membrane protein skeleton that is attached to the bilayer via linker proteins.
The integrity of the membrane relies on vertical interactions between the skeleton and the bilayer, as well as on horizontal interactions within the membrane skeletal network.
ERYTHROCYTE MEMBRANE ABNORMALITIES
Inherited membrane protein defects disrupt the membrane architecture and alter the shape of the cell, resulting in hemolytic anemia as illustrated in Figure 13–1.
Protein defects that compromise vertical interactions between the membrane skeleton and the lipid bilayer result in destabilization of the bilayer, loss of membrane microvesicles, and spherocyte formation.
Protein defects affecting horizontal protein interactions within the membrane skeletal network disrupt the skeleton, resulting in defective shape recovery and elliptocytes and other abnormal red cell shapes.
Red cell membrane disorders exhibit significant heterogeneity in their clinical, morphologic, laboratory, and molecular characteristics.
Blood films from patients with erythrocyte membrane disorders. A. Normal blood film. B. Hereditary spherocytosis with dense spherocytes. C. Southeast Asian ovalocytosis with large ovalocytes exhibiting a transverse ridge. D. Hereditary elliptocytosis with elongated elliptocytes and some poikilocytes. E. Hereditary stomatocytosis with cup-shaped stomatocytes. F. Hereditary abetalipoproteinemia with acanthocytes. (Reproduced with permission from Lichtman MA, Shafer MS, Felgar RE, et al: Lichtman’s Atlas of Hematology 2016. New York, NY: McGraw Hill; 2017. www.accessmedicine.com.)
Table 13–1 summarizes the relationship between red cell membrane proteins and disease phenotype.
TABLE 13–1 ERYTHROCYTE MEMBRANE PROTEIN DEFECTS IN INHERITED DISORDERS OF RED CELL SHAPE
|Protein ||Disorder ||Comment |
|Ankyrin ||HS ||Most common cause of typical dominant HS |
|AE1 (band 3) ||HS, SAO, NIHF, HAc ||“Pincered” HS spherocytes seen on blood film before splenectomy; SAO results from 9 amino acid deletion |
|β-Spectrin ||HS, HE, HPP, NIHF ||“Acanthocytic” spherocytes seen on blood film before splenectomy; location of mutation in β-spectrin determines clinical phenotype |
|α-Spectrin ||HS, HE, HPP, NIHF ||Location of mutation in α-spectrin determines clinical phenotype; α-spectrin mutations most common cause of typical HE |
|Protein 4.2 ||HS ||Primarily found in Japanese patients |
|Protein 4.1 ||HE ||Found in certain European and Arab populations |
|GPC ||HE ||Concomitant protein 4.1 deficiency is basis of HE in GPC defects |
Definition and Epidemiology