Young sickle red cells have a propensity to adhere to small post-capillary venules. This has been demonstrated both in the mesenteric circulation (ex vivo) as well as in vivo in the cremaster muscle of sickle transgenic mice. Evidence exists that obstruction of the microcirculation occurs primarily in the venule side, preceded by adhesion of young sickle red cells, and completed by the trapping of dense cells and ISCs in areas bedecked with adhered red cells.
The mechanism of adhesion is not completely understood and is probably multifactorial, but von Willebrand factor and the vibronectin receptor (avP3) appear to be excellent candidates, since antibodies against either of the members of the pair inhibit adhesion in living circulatory preparations. Other proposed mechanisms have not been fully validated in micro-circulatory preparations, nor have they been demonstrated to be operative in small venules.
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