Src family kinases inhibition by dasatinib blocks initial and subsequent platelet deposition on collagen under flow, but lacks efficacy with thrombin generation.

ABSTRACT: Kinase inhibitors can pose bleeding risks as platelet signaling evolves during clotting. Using microfluidics (200 s^-1 wall shear rate) to perfuse Factor XIIa-inhibited or thrombin-inhibited whole blood (WB) over collagen ± tissue factor (TF), we explored the potency of the Src family kinase (SFK) inhibitor dasatinib or the spleen tyrosine kinase (Syk) inhibitor GS-9973 present at clot initiation or added after 90 s (via rapid switch to inhibitor-pretreated WB). When initially present, dasatinib potently inhibited platelet deposition on collagen (no TF). Furthermore, dasatinib immediately inhibited subsequent platelet deposition when introduced 90 s after clot initiation. However, when thrombin was generated, dasatinib was markedly less potent against platelet deposition on colla

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7306827 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature