RT Book, Section A1 Coetzer, Theresa L. A2 Prchal, Josef T. A2 Lichtman, Marshall A. SR Print(0) ID 1184011737 T1 Erythrocyte Membrane Disorders T2 Williams Hematology The Red Cell and Its Diseases YR 2022 FD 2022 PB McGraw Hill PP New York, NY SN 9781264269075 LK hemonc.mhmedical.com/content.aspx?aid=1184011737 RD 2024/03/28 AB SUMMARYThe human erythrocyte membrane consists of a lipid bilayer containing transmembrane proteins and an underlying membrane skeleton that is attached to the bilayer by linker protein complexes. The membrane is critical in maintaining the unique biconcave disk shape of the erythrocyte and enabling it to withstand circulatory shear stress. The integrity of the membrane is ensured by vertical interactions between the skeleton and the transmembrane proteins, as well as by horizontal interactions between skeletal proteins. Inherited defects of membrane proteins compromise these interactions and alter the shape and deformability of the cells, which ultimately results in their premature destruction, seen clinically as hemolytic anemia. The disorders are typically inherited in an autosomal dominant manner and exhibit significant clinical, laboratory, biochemical and genetic heterogeneity.Hereditary spherocytosis (HS) is a common condition characterized by spherically shaped erythrocytes on the blood film, reticulocytosis, and splenomegaly. The underlying defect is a deficiency of one of the membrane proteins, including ankyrin, anion exchanger-1 (AE1, formerly band 3), α-spectrin, β-spectrin, or protein 4.2. These defects weaken vertical membrane interactions, resulting in loss of membrane and surface area. Spherocytes have diminished deformability, which predisposes them to entrapment and destruction in the spleen. Hereditary elliptocytosis (HE) is characterized by the presence of elliptical erythrocytes on the blood film. The principal abnormality affects horizontal membrane protein interactions and typically involves α-spectrin, β-spectrin, protein 4.1R, or glycophorin C. The membrane skeleton is destabilized and unable to maintain the biconcave disk shape, which manifests as an elliptical distortion of the cells in the circulation. Hereditary pyropoikilocytosis (HPP) is a rare, severe hemolytic anemia characterized by markedly abnormal erythrocyte morphology resulting from defective spectrin. South East Asian Ovalocytosis (SAO) is largely asymptomatic and is caused by a defect in AE1. The blood film shows large oval red cells with a transverse ridge across the central area. Acanthocytosis is typified by contracted, dense erythrocytes with irregular projections, which may be seen in patients with severe liver disease, abetalipoproteinemia, various neurologic disorders, certain aberrant red cell antigens, and postsplenectomy. Stomatocytosis is a rare group of inherited disorders associated with abnormal membrane permeability and red cell cation content, which either cause overhydration or dehydration of the cells.