Sickle Cell Anemia
Sickle Cell Anemia (SCA) is a group of hereditary blood disorders caused by a genetic mutation that affects hemoglobin, the molecule that delivers oxygen throughout the body via red blood cells. Hemoglobin with this mutation is referred to as HbS. HbS and normal hemoglobin (normally referred to as HbA) is a protein in red blood cells that carries oxygen from the lungs to the body’s tissues and returns carbon dioxide from the tissues back to the lungs. Hemoglobin accomplishes this function by binding and then releasing oxygen through a process by which the hemoglobin molecule changes its shape to have a high affinity for oxygen in the lungs, where oxygen is abundant, and low affinity for oxygen in the tissues, where oxygen must be released. Oxyhemoglobin, is formed in the lungs during respiration, when oxygen binds to it, while deoxygenated hemoglobin, is formed when oxygen molecules are removed from the binding site as blood flows from the lungs to the body.
In patients with sickle cell anemia, deoxygenated HbS molecules react to one another to form long rods or polymers, under very low oxygen conditions. These rods are rigid and remain within a red blood cell, much like a “sword within a balloon” eventually destroying the cell (hemolysis). While the typical sickle shape of cells containing these rods has defined the disease, several other anomalies are present in SCA patients. In particular is a unique fatty acid profile that also defines SCA patients that is present in patients worldwide. This profile suggests an interaction between HbS and the red blood cell membrane itself. When this occurs, the membrane fatty acid composition and physical characteristics change, In addition, the interaction of HbS with the cell membrane fatty acid trigger this change signaling a pro-inflammatory state. Hence a patient with SCA is always in an inflammatory state.
So, once a cell becomes depleted of certain fatty acids and is in the pro-inflammatory state, a cascade occurs in the cell itself releasing various chemicals that cause aggregation and clumping of cells within blood vessels. Not only do red blood cells clump to each other, but so do the white blood cells. These “stick” together and to the walls of the veins and arteries through which they flow. This clumping slows down the transit time of blood flowing through tissue resulting in extraordinary deoxygenation of the HbS. The blockage of blood flow by this aggregation causes initial intense pain and tissue damage. Furthermore, the continued deoxygenation stimulates the polymerization noted above and the typical sickle cell shape forms as the normally round and flexible red blood cell becomes rigid and elongated. Sickled red blood cells do not flow properly in the bloodstream; they further clog small blood vessels and reduce blood flow to the organs. These events are referred to as vaso-occulsive events or VOCs.
Sickled red blood cells also die earlier than normal red blood cells and the bone marrow cannot make enough new red blood cells (called erythrocytes) to replenish the dying ones, causing a constant shortage of red blood cells. This results in inadequate oxygen delivery, or hypoxia, to all body tissues, leading to multi-organ failure and premature death. The chronic destruction of red blood cells and inability to replace them at the same rate they are being lost results in the anemia which is also associated with the disease.