Venous puncture wound hemostasis results in a vaulted thrombus structured by locally nucleated platelet aggregates
Sung W. Rhee, Irina D. Pokrovskaya, Kelly K. Ball, Kenny Ling, Yajnesh Vedanaparti, Joshua Cohen, Denzel R. D. Cruz, Oliver Zhao, Maria A. Aronova, Guofeng Zhang, Jeffrey A. Kamykowski, Richard D. Leapman, Brian Storrie
Abstract
Abstract Primary hemostasis results in a platelet-rich thrombus that has long been assumed to form a solid plug. Unexpectedly, our 3-dimensional (3D) electron microscopy of mouse jugular vein puncture wounds revealed that the resulting thrombi were structured about localized, nucleated platelet aggregates, pedestals and columns, that produced a vaulted thrombus capped by extravascular platelet adherence. Pedestal and column surfaces were lined by procoagulant platelets. Furthermore, early steps in thrombus assembly were sensitive to P2Y 12 inhibition and late steps to thrombin inhibition. Based on these results, we propose a Cap and Build, puncture wound paradigm that should have translational implications for bleeding control and hemostasis.