The effect of Syk inhibition in platelets- New therapy outlook for thrombotic and immune thrombocytopenia?

Abstract

Spleen tyrosine kinase (Syk) inhibitors have been shown to inhibit signal transduction of Fc-gamma activating receptors, which play a key role in antibody-mediated disorders. In the proposed study, the elucidation of various aspects of Syk inhibition in human platelets was pursued. By analyzing in detail platelet behavior in flow cytometry, it was possible to demonstrate that Syk inhibition is able abrogate FcγRIIA mediated platelet activation and interrupts the expression of apoptotic and procoagulant platelet markers in-vitro. By exploring the opportunities of Syk inhibition in healthy platelets, different effects of Syk inhibition on platelet function were elucidated. While investigating the effect of Syk inhibition 60 in ex-vivo models of VITT and ITP, two platelet disorders with drastically different pathogenesis, it became apparent how the inhibition of Syk can prevent negative biological effects in platelets conveyed by antibodies. These results encourage further research with the outlook for new therapy approaches.