Central to the interplay between the malaria parasite and the human coagulation system is the serine protease thrombin, which directly coordinates the balance between a procoagulant state by fibrin generation and an anticoagulant state by the activation of protein C. Additionally, depending on the site of substrate cleavage, thrombin can induce either cytoprotection of endothelial barrier function or proinflammatory effects and barrier dysfunction through activation of protease-activated receptor-1 (PAR1), -3, and -4 signaling (23). This evidence concerns the gene F2R and malaria.