The complex pathophysiology and effects of SCD goes beyond red blood cells (RBCs)1–3
Early damage to, and microtearing of, the blood vessel wall induces endothelial inflammation and may lead to chronic vascular damage
Over time, ongoing damage and repeated injury to the blood vessel wall can result in activation of endothelial cells
The chronic inflammatory environment within blood vessels leads to increased expression of adhesion molecules on endothelial and blood cells inducing multicellular adhesion
Multicellular adhesion of endothelial and blood cells reduces and blocks blood flow to organs
Activated endothelial cells initiate a complex cascade of adhesive interactions with RBCs, white blood cells (WBCs) and platelets that lead to ongoing vaso‑occlusion
A reduction in blood flow promotes hypoxic conditions and, along with consequent occlusion of the vessel, helps to induce HbS polymerisation
Under hypoxic conditions,
HbS undergoes polymerisation
HbS polymers distort the shape of RBCs, resulting in dense and sickle-shaped cells that can cause endothelial tearing
The inflexibility of sickled RBCs contributes to their premature destruction, and the by‑products of haemolysis cause endothelial inflammation
A decrease in the number of RBCs due to premature destruction leads to lower haemoglobin levels and subsequent anaemia
SCD and the risk of iron overload
Frequent blood transfusions are used to help treat SCD‑associated complications (most notably anaemia), which can predispose SCD patients to iron overload.6–8
Abbreviations: HbS, sickle haemoglobin; RBC, red blood cell; SCD, sickle cell disease; WBC, white blood cell.
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