The molecular basis of disorders of the red cell membrane.

Haemolytic anaemia denotes a state in which there is an increased rate of red cell destruction. It can be classified on the basis of whether the defect is intrinsic to the red cell or extrinsic to the red cell (that is, a problem in the surrounding environment). Intrinsic defects include defects in the red cell membrane, defects in the red cell enzymes, and defects in globin structure and synthesis. They are generally congenital although there are a few rare acquired intrinsic erythrocyte defects (for a full discussion of the causes of haemolytic anaemia, see Lee et al, 1993). In this review I shall provide an overview of the molecular basis of the intrinsic defects of the red cell membrane. Although the majority of red cell membrane defects are congenital, we now have considerable knowledge of some acquired intrinsic red cell defects such as paroxysmal nocturnal haemoglobinuria which I shall also discuss. The red cell membrane The red cell membrane consists of a lipid bilayer which contains 95% cholesterol and phospholipids. It is studded with proteins which are involved in transport or signalling. The inner surface of the bilayer is a lattice of proteins which make up the membrane skeleton or red cell skeleton (fig 1). Skeletal proteins include spectrin á and â chains which form dimers and tetramers. These are linked horizontally to actin and protein 4.1. There are many additional proteins including adducin and dematin. Vertically the skeleton is linked to the bilayer. The anion exchanger (AE1) is a transporter protein which is connected via ankyrin to spectrin. Protein 4.2 interacts with AE1. Protein 4.1, protein p55, and glycophorins C and D are attached vertically. The outer surface of the bilayer has a number of linked components including the glycosylphosphatidylinositol (GPI) anchored proteins. The