The complex pathophysiology and effects of SCD goes beyond red blood cells (RBCs)1–3

Vaso-occlusion1

Early damage to, and microtearing of, the blood vessel wall induces endothelial inflammation and may lead to chronic vascular damage

Chronic vascular
damage1,4

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Over time, ongoing damage and repeated injury to the blood vessel wall can result in activation of endothelial cells

Inflammation and
cell activation1,4

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The chronic inflammatory environment within blood vessels leads to increased expression of adhesion molecules on endothelial and blood cells inducing multicellular adhesion

Multicellular
adhesion4,5

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Multicellular adhesion of endothelial and blood cells reduces and blocks blood flow to organs

Vaso-occlusion1

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Activated endothelial cells initiate a complex cascade of adhesive interactions with RBCs, white blood cells (WBCs) and platelets that lead to ongoing vaso‑occlusion

Anaemia1,3

A reduction in blood flow promotes hypoxic conditions and, along with consequent occlusion of the vessel, helps to induce HbS polymerisation

HbS
polymerisation1

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Under hypoxic conditions,
HbS undergoes polymerisation

Sickling1

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HbS polymers distort the shape of RBCs, resulting in dense and sickle-shaped cells that can cause endothelial tearing

Haemolysis4

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The inflexibility of sickled RBCs contributes to their premature destruction, and the by‑products of haemolysis cause endothelial inflammation

Anaemia4

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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.

References

  1. Conran N, et al. Hemoglobin. 2009;33(1):1–16.
  2. Piel FB, et al. N Engl J Med. 2017;376(16):1561–1573.
  3. Chirico EN, Pialoux V. IUBMB Life. 2012;64(1):72–80.  
  4. Zhang D, et al. Blood. 2016;127(7):801–809.
  5. Habara A, Steinberg MH. Exp Biol Med (Maywood). 2016;241(7):689–696.
  6. McCavit T, Desai P. National Heart, Lung and Blood Institute. 2014. Available at: https://www.nhlbi.nih.gov/sites/default/files/media/docs/sickle-cell-dis... Last accessed March 2021.
  7. Claster S, Vichinsky EP. BMJ 2003;327:1151–1155.
  8. Davis BA, et al. BJH 2017;176:179–191.
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