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Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.206 Figure 4 Novel therapeutic targets to differentiate thrombosis from haemostasis Figure 4 | Novel therapeutic targets to differentiate thrombosis from haemostasis. Inhibition of platelets with collagen and von Willebrand factor (vWF) exposed at sites of ruptured atheroma can be achieved with inhibitors of platelet glycoprotein (GP) VI (revacept) and GPIb (caplacizumab), respectively. Inhibition of the intracellular lipid kinase phosphatidylinositol 3-kinase-β (PI3Kβ), which acts downstream of ligand-bound GPVI, GPIb, and the P2Y purinoceptor 12 (P2Y12) to mediate GPIIb/IIIa adhesion, selectively targets platelet adhesion under high shear, as found at sites of stenotic lesions. New inhibitors of proteinase-activated receptor (PAR) 1 (parmodulins) and PAR4 (BMS-986120) have been described and seem to have minimal effects on haemostasis. Novel approaches to inhibiting GPIIb/IIIa include conformation-specific, single-chain variable fragment (scFv) antibodies that bind only to the active conformation of GPIIb/IIIa; specifically targeting integrin outside-in signalling with small molecule inhibitors, such as myristoylated peptide ExE peptide motif (mP6); and inhibition of protein disulfide-isomerase (PDI), which is important for GPIIb/IIIa activation in addition to fibrin formation. Conformation-specific scFvs can be linked with agents such as CD39, which hydrolyses ADP to deliver antithrombotic effects directly to sites of thrombus formation. McFadyen, J. D. et al. (2018) Current and future antiplatelet therapies: emphasis on preserving haemostasis Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.206