Erythrocyte/endothelial interactions and the vasocclusive severity of sickle cell disease.

Sickle - but not normal - RBC adhere to human endothelial cells. This abnormal behavior requires neither deoxygenation nor frank morphologic distortion of the sickle RBC. Although adherence increases as RBC density increases (presumably paralleling the accumulation of membrane damage), even the least dense sickle and youngest sickle RBC adhere abnormally to endothelium. Data suggest that adherence to endothelium is a consequence of an aberrancy of sickle RBC membrane surface charge topography (clumping of NANA), which it turn may be related - at least in part - to abnormal calcium accumulations in sickle RBC. The propensity for endothelial adherence varies greatly among patients with sickling disorders, and it correlates positively and significantly with clinical vasocclusive severity. The inherent tendency for endothelial adherence of washed sickle RBC from a given patient shows little temporal variation, regardless of the patient's state of health. However, plasma factors which may fluctuate during concurrent illness have an enhancing effect of RBC/endothelial interactions in vitro and may increase the likelihood for vasocclusion by increasing adherence in vivo. It is not yet clear whether adherence is in itself a fully sufficient condition for the development of vasocclusion. It may be that RBC adherence to endothelium initiates vasocclusion by impeding microvascular blood flow and thereby allowing the secondary occurrence of reversible sickling, thus leading to pain crisis and organ infarction.