Expert
Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 8; Issue 9; 28 April 2006 Abstract
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A working model of pathophysiology
of vaso-occlusion in sickle cell disease
Catherine
Madigan and Punam Malik
Author
contact details
Figure 2. A working model
of pathophysiology of vaso-occlusion in sickle cell disease. This figure illustrates
the complexity of the pathophysiology of sickle cell anemia. The primary event
is HbS polymerisation causing sickling of RBCs. Factors that promote cellular
dehydration, tissue hypoxia, and leukocyte or endothelial cell activation are
all involved in generating vaso-occlusion. RBCs in SCA have abnormal ion transport
properties, causing cellular dehydration. This promotes HbS polymerisation and
thereby vaso-occlusion. The increased haemolysis in SCA leads to tissue hypoxia
directly through the resultant anaemia, and indirectly through inactivation of
nitric oxide (NO) and consequent loss of vasodilation. Leukocyte activation in
SCA is promoted by decreased NO availability, chronic ischemia–reperfusion
injury, and possibly by erythroblast-produced placenta growth factor (PlGF). Activated
leukocytes themselves are more adherent than resting leukocytes. Further, they
activate the endothelium itself, increasing its adherent properties. Thus, activated
leukocytes lead to the adhesion of both leukocytes and RBCs to the endothelium,
contributing to vaso-occlusion. Adhesion to the endothelium is also promoted by
the anaemia-driven increased reticulocytosis, because reticulocytes are more adherent
than mature RBCs. These processes are elaborated upon further in this review.
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