Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis

Current understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range of descriptive titles and attributes. We identify striking overlaps in the reported characteristics of these platelets, which imply a single subpopulation of versatile platelets and thus suggest that their commonality requires unification of their description. We therefore propose the term procoagulant platelet as the unifying terminology. We discuss the agonist requirements and molecular drivers for the dramatic morphological transformation platelets undergo when becoming procoagulant. Finally, we provide perspectives on the biomarker potential of procoagulant platelets for thrombotic events as well as on the possible clinical benefits of inhibitors of carbonic anhydrase enzymes and the water channel Aquaporin-1 for targeting this subpopulation of platelets as antiprocoagulant antithrombotics.