**1. Introduction**

The red blood cell (RBC) lives in the bloodstream about 120 days (4 months) providing oxygen and nutrients to all the tissue cells. A large part of their passage is through capillaries with a diameter ranging from 3 to 8 μm which is less than its mean cell diameter, of about 7.5 μm. Accordingly to reach all the cells, the RBCs have to adapt their shape to the dynamically changing flow conditions especially in microcirculation. This is due to its ability to deform and pass through small capillaries and recover their initial shape [1]. The basis of this extreme deformability is its

characteristic discoid shape with a biconcave profile (**Figure 1a**, **b**). RBC deformability significantly affects blood viscosity as its decrease elevates the blood viscosity, the flow resistance and, in turn, the blood pressure [3].

RBC deformability is the result of three cell properties: (a) shape (bi-concave discocyte) depending on the surface/volume (S/V) ratio, (b) viscosity depending on intracellular haemoglobin concentration and its physicochemical state and (c) viscoelasticity largely determined by the cytoskeleton, an actin-spectrin network that underlies the lipid leafet of the membrane [4]. This structure consists of long twisted strands of alpha and beta spectrin and actin filaments that form the inner shell of the RBC and provides the basis of cell deformability (**Figure 1c**). Spectrin is bound to the lipid bilayer of the membrane at sites containing the anion exchanger, band 3 via cytoskeletal proteins, ankyrin and adducin. Some of the transmembrane proteins (such as glycophorin A) are RBC antigens and contribute to the blood group system [5]. Due to their discoid form, the normal RBCs have an S/V ratio of about 1.56, indicating an excess of the surface (membrane) with regard to the volume. This allows RBCs to change their shape without increasing the surface and, subsequently, to be highly deformable in the bloodstream and in the spleen. The spleen is a highly

*Congenital Defects with Impaired Red Blood Cell Deformability – The Role of Next-Generation… DOI: http://dx.doi.org/10.5772/intechopen.109637*

**Figure 2.** *Spleen red pulp observed with scanning electron microscope. RBCs trespassing the inter-endothelial slits.*

vascularised organ, with a blood flow that represents around 6% of the cardiac flow. Its vasculature is formed by a complex network of capillaries and sinuses with endothelial cells that are anastomosed together without junction. Under the changes of the capillary diameter, the inter-endothelial slits (IESs) of about 0.2–0.4 μm of diameter are created, and the RBCs are obliged to pass through these IESs suffering an extreme, but reversible, deformation (**Figure 2**). Only the cells with normal deformability can overcome the IES, and due to this, this system is considered a particular splenic barrier for RBC defects [6]. When the S/V ratio for healthy RBCs is beyond the "physical fitness test" to pass through the IES, the cells are unable to adapt and are easily trapped and destroyed by the spleen [7].
