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. 2018 Oct 31;104(4):806–818. doi: 10.3324/haematol.2018.205724

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Figure 6. — Scheme for metabolic flux in stimulated platelets and sites of action of small-molecule modulators. Stimulated platelets switch to aerobic glycolysis through negative regulation of pyruvate kinase M2 and pyruvate dehydrogenase enzyme activities. The consequent increase in flux through the pentose phosphate pathway generates NADPH that fuels ROS generation by NADPH oxidase. ROS signaling in turn mediates platelet activation, thrombosis and hemostasis. Small-molecule modulators that reverse this metabolic adaptation inhibit platelet activation and impair thrombus formation. DASA: diarylsulfonamide; DCA: dichloroacetate; DHEA: dehydroepiandrosterone sulphate; NOX: NADPH oxidase; PDH: pyruvate dehydrogenase; PDK: pyruvate dehydrogenase kinase PKM2: pyruvate kinase M2; PPP: pentose phosphate pathway; ROS: reactive oxygen species.