Description:

This session will highlight the contribution of thrombin and platelet gradients, factor XIII, and red blood cells (RBC) to thrombus formation and clot structure.

Dr. Stalker will discuss the thrombin and platelet gradients in the developing thrombus. Heterogeneity in the extent of platelet activation during hemostasis and thrombosis can be attributed to distinct spatiotemporal distribution of individual platelet agonists at a site of injury. Agonist distribution is regulated in part by the physical properties of local microenvironments that are created in the spaces between platelets as a platelet mass evolves. Studies examining the coordination of platelet signaling in time and space continue to increase our understanding of hemostasis and thrombosis.

Dr. Wolberg will discuss the role of factor XIII in retaining RBC in venous clots. A defining characteristic of venous thrombi is their high red blood cell content (so-called “red thrombi”); however, mechanisms that mediate red blood cell presence in thrombi have remained elusive. Factor XIII(a) is a transglutaminase that binds fibrin(ogen) and stabilizes the fibrin network. Recent findings reveal that factor XIII activity also mediates red blood cell retention in clots and is an important determinant of thrombus composition during venous thrombosis.

Dr. Ariens will discuss the contribution of RBC to clot structure. A specific integrin receptor mediating the interaction between the RBC and fibrin/ogen has been characterized, which is comparable in strength as that between fibrin/ogen and platelets. Furthermore, RBC incorporated into clots contributes to reshape and impermeability of the clot. Changes in permeability due to abnormalities in fibrin or interactions with RBC are important determinants of clot stability and thrombosis.