Challenges in platelet transfusion: From storage to alloimmunization

Patients with low platelet counts or dysfunctional platelets are often treated with platelet transfusions in order to prevent bleeding. The shelf life of platelets is limited to 5-7 days, and storage of platelets coincides with loss of platelet functionality. This deleterious changes are called the platelet storage lesion. In the first part of this thesis we study the effect of platelet storage on several in vitro platelet parameters, including surface glycosylation, platelet activation, expression of surface proteins and aggregation. Besides, a proteomic study was performed on stored platelets to evaluate changes in protein levels during platelet storage. In addition to current limitations in the efficient storage of platelet concentrates, the development of anti-platelet antibodies provides a major challenge in the care for platelet transfusion-dependent patients In the second part of this thesis the effect of anti-HLA antibodies on platelets was studied. We showed that a subset of anti-HLA antibodies induces FcγRIIa-dependent platelet activation which promotes in vitro phagocytosis of platelets by macrophages. Furthermore, the effect of anti-HLA antibodies on complement activation on platelet surfaces was studied. Our observations suggest that anti-HLA antibodies can contribute to enhanced clearance of platelets upon transfusion by inducing complement activation