Abstract
Physiologically, upon platelet activation, uncontrolled propagation of thrombosis is prevented by regulating mechanisms which affect the expression and function of either platelet adhesion receptors or integrins. Receptor ectodomain shedding is an elective mechanism which is mainly involved in down-regulation of adhesion receptors GPIbα and GPVI. Platelet integrin α(IIb)β(3) can also be modulated with a calpain-dependent proteolytic cleavage. In addition, activating signals may induce the internalization of expressed receptors to selectively down-regulate their intensity. Alternatively, further activation of platelets is associated with microvesiculation as a none-selective mechanism which leads to the loss of membrane- bearing receptors. In a non-physiological condition, the storage of therapeutic platelets has also shown to be associated with the unwilling activation of platelets which triggers receptors down-regulation via aforementioned different mechanisms. Notably, herein the changes are time-dependent and not controllable. While the expression and shedding of pro-inflammatory molecules can induce post-transfusion adverse effects, stored-dependent loss of adhesion receptors by ectodomain shedding or microvesiculation may attenuate post-transfusion adhesive functions of platelets causing their premature clearance from circulation. In its first part, the review presented here aims to describe the mechanisms involved in down-regulation of platelet adhesion receptors. It then highlights the crucial role of ectodomain shedding and microvesiculation in the propagation of "platelet storage lesion" which may affect the post-transfusion efficacy of platelet components.