Figure 7:

PAR1/4 and GPVI play redundant roles in platelet activation and contraction in TEG. (1) Analysis of clot formation speed and clot strength in TEG is performed by recalcifying citrated whole blood and activating with kaolin to initiate coagulation. (2) Within several minutes, thrombin generation initiates fibrinogen cleavage to fibrin, which polymerizes and crosslinks. Additionally, thrombin activates platelets through protease activated receptors (PARs) (PAR4 on mouse platelets, PAR1 and PAR4 on human platelets). Both fibrin polymerization and platelet activation contribute to the speed of clot formation (α-angle). (3) As more fibrin is generated, platelets can also bind fibrin via GPVI for additional activation signaling, resulting in robust αIIbβ3 integrin activation and platelet-mediated contraction of the fibrin clot. Clot strength (MA) is entirely dependent on platelet contraction. (4) The end result is a tightly contracted whole blood clot with contracting platelets bound to fibrin. While loss of either platelet PARs or GPVI alone has limited impact on TEG parameters, loss of both leads to TEG traces similar to platelet-depleted blood samples. Created with BioRender.com.