Formation and Relevance of Platelet Subpopulations

Platelets are important players in the hemostatic system, acting as guardians of vessel integrity. When they come across a breach in the vessel wall, they quickly adhere to the damaged surface, secrete activating and adhesive compounds from their secretory granules, recruit additional platelets into a growing platelet plug and support the action of the coagulation system. In the past decades, it has become clear that platelets form functionally different platelet subpopulations. The aggregatory platelets build the platelet plug, whereas the procoagulant subpopulation support and direct the actions of the coagulation system. The aim of this thesis was to examine the formation and features of the different platelet subpopulations, and elucidate their respective roles in hemostasis. Platelet lysosomal secretion is not well characterized. In Paper I, we found that lysosomal secretion, detected as LAMP-1 surface exposure, occur upon potent platelet stimulation including secondary activation by ADP. This is regulated by the endothelial platelet inhibitors nitric oxide and prostacyclin. As observed in Paper II, lysosomal secretion might also be of clinical relevance as a quality indicator for platelet concentrates used for transfusion, an area were quality control may become increasingly important in the future. Among several evaluated platelet activation markers, platelet LAMP-1 exposure and the ability to form procoagulant platelets may be useful as novel indicators of platelet responsiveness. Moreover, the ability to form procoagulant platelets varies extensively between individuals, something we established in Paper III. Here we also present a novel flow cytometry protocol enabling the simultaneous investigation of 6 different platelet activation markers. Using this protocol we investigate the formation of procoagulant platelets and reveal that only a subpopulation of platelets may become procoagulant. Further we show that this is dependent on the agonist stimulation a