Objective: Our objective is to review the role of adhesion molecules,
cytokines, and inflammation in the abnormal adherence of sickle red bl
ood cells to vascular endothelia in the pathogenesis of vascular compl
ication in patients with sickle cell anemia. Data Sources: The MEDLINE
database was used to review the hematologic, immunologic, and allergy
literature in English with respect to the adhesion molecules involved
in sickle hematopoiesis and vascular complications. Study Selection:
Studies selected for review were those that identified the adhesion mo
lecules involved in reticulocyte-endothelial adhesion and the influenc
e that cytokines, infections, and atopy have upon the expression of th
ese molecules. Results: In sickle cell disease, a constant low level o
f inflammation caused by abnormal adhesion of sickle erythrocytes to e
ndothelial cells in the microvasculature produces low-level tissue isc
hemia. Allergic and infectious inflammations are likely to lead to inc
reased sickle erythrocyte trapping in the microvascular endothelia whi
ch progresses to vessel obstruction, end organ ischemic damage, and dy
sfunction. Conclusion: The identification of underlying immune defects
that predispose patients to infections and inflammation needs to be e
mphasized. Anti-inflammatory medications, anti-adhesion molecule monoc
lonal antibodies, and adhesion molecule binding-site analogs may have
a future in the treatment of the acute vascular complications of sickl
e cell disease.