Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


  • 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.


  • 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.

Table 13–1 summarizes the relationship between red cell membrane proteins and disease phenotype.

|Download (.pdf)|Print
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

AE1, anion exchanger-1 (band 3); GPC, glycophorin C; HAc, hereditary acanthocytosis; HE, hereditary elliptocytosis; HPP, hereditary pyropoikilocytosis; HS, hereditary spherocytosis; NIHF, nonimmune hydrops fetalis; SAO, Southeast Asian ovalocytosis.


Definition and Epidemiology

  • Hereditary spherocytosis (HS) is characterized by a decrease ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.