Multicellular adhesion plays a major role in vaso-occlusion and vaso-occlusive crises^1,2

Sickle cell disease (SCD) goes beyond red blood cells (RBCs) and progresses to a chronic inflammatory vascular disorder early in a patient’s life.^1-3 This chronic inflammatory state leads to increased multicellular adhesion and plays a major role in the pathophysiology of vaso-occlusion and vaso-occlusive crises (VOCs)—the clinical hallmark of SCD.^1,2,4

Take this 3D interactive tour to see how SCD progresses to a chronic inflammatory vascular disorder

VOCs, the clinical hallmark of SCD, are largely driven by a process called multicellular adhesion, during which RBCs, white blood cells (WBCs), and platelets aggregate and adhere to endothelial cells of the blood vessel wall.^1-3

The blood vessels of those with SCD are in a chronic state of inflammation, leading to the increased expression of cell-surface proteins called adhesion molecules, including E-, L-, and P-selectin.^1,3,5,6

The Pathophysiology of Sickle Cell Disease

Watch this video to learn more about SCD and the cause of vaso-occlusion and VOCs

Vaso-occlusion, haemolysis, and anaemia: the complex effects of sickle cell disease go beyond red blood cells^1,7,8

Vaso-Occlusion¹

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

Anaemia^1,8

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

Chronic vascular damage and HbS polymerisation

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

Under hypoxic conditions, HbS undergoes polymerisation

Inflammation and Cell Activation and sickled red blood cells

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

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

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

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

Activated endothelial cells initiate a complex cascade of adhesive interactions with RBCs, WBCs, and platelets that lead to ongoing vaso-occlusion

A decrease in the number of RBCs due to premature destruction leads to lower haemoglobin levels and subsequent anaemia

See how ongoing and often silent vaso-occlusion may result in VOCs—the clinical hallmark of SCD^1,2,4

References: 1. Conran N, Franco-Penteado CF, Costa FF. Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin. 2009;33(1):1-16. 2. Puri L, Nottage KA, Hankins JS, Anghelescu DL. State of the art management of acute vaso-occlusive pain in sickle cell disease. Paediatr Drugs. 2018;20(1):29-42. 3. Zhang D, Xu C, Manwani D, Frenette PS. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood. 2016;127(7):801-809. 4. Ballas SK, Gupta K, Adams-Graves P. Sickle cell pain: a critical reappraisal. Blood. 2012;120(18):3647-3656. 5. Kanter J, Kruse-Jarres R. Management of sickle cell disease from childhood through adulthood. Blood Rev. 2013;27(6):279-287. 6. Kappelmayer J, Nagy B. The interaction of selectins and PSGL-1 as a key component in thrombus formation and cancer progression. Biomed Res Int. 2017;2017(6138145):1-18. doi: 10.1155/2017/6138145. 7. Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;376(16):1561-1573. 8. Chirico EN, Pialoux V. Role of oxidative stress in the pathogenesis of sickle cell disease. IUBMB Life. 2012;64(1):72-80. 9. Habara A, Steinberg MH. Genetic basis of heterogeneity and severity in sickle cell disease. Exp Biol Med (Maywood). 2016;241(7):689-696.