Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease

Platelets are the key cell types in haemostasis after vascular injury and crucially contribute to thrombus formation. In addition to their aggregation and clot contraction functions after stimulation by soluble agonists or extracellular matrix proteins, platelets can adopt a highly activated state known as procoagulant activation. Procoagulant platelets influence the pathophysiology underlying various cardiovascular diseases, including myocardial infarction, stroke and deep vein thrombosis. Findings described in the past decade position procoagulant platelets at the dynamic intersection between thrombosis and inflammation. In this Review, we discuss the expanding research on procoagulant platelets, describing how this platelet activation state contributes to macrovascular and microvascular clot formation in cardiovascular diseases. We summarize the key receptors and signalling pathways that control platelet procoagulant activation and that distinguish the procoagulant phenotype from other platelet activation states. Finally, we highlight the clinical significance of platelet procoagulant activation and discuss how the individual pathways involved in this activation can be targeted with the use of both readily available and novel therapeutic approaches, providing a framework for future research that might lead to new diagnostic and therapeutic applications in cardiovascular disease, septic inflammation and immune complex-mediated diseases.