Figure 1.

Overview of the coagulation and clotting factor signaling. Increased levels of platelet blood counts and coagulation cascade activation are determinants of a hypercoagulable state. Platelet production (thrombopoiesis) at the bone marrow by megakaryocytes determines platelet counts (A). Upon vascular damage, platelets become activated, adhere to the vascular endothelium and promote neutrophil activation and NET release (B). Platelets, Neutrophils and Endothelial cells become activated and promote thrombus formation, a process mediated by the coagulation cascade activation (C). TF, a transmembrane receptor, initiate the extrinsic blood coagulation pathway once bound in a quaternary complex with FVIIa, that is inhibited by TFPI. The cleavage of FX by FVIIa gives rise to FXa, which in turn cleaves prothrombin into thrombin. Thrombin, FXa and other proteases such as Plasmin, MMPs, and aPC can activate PARs, which signal through PLC-PKC-Ca²⁺ Pathway and activate other signaling pathways such as NFkB and ERK1/2, leading to platelet, neutrophil and EC activation. This pathway also promotes cancer cell growth and invasion. PAR activation leads to receptor internalization, which classically occurs through the endolyosomoal pathway. aPC, activated Protein C; ERK1/2, Extracellular signal-regulated protein kinases 1 and 2; EC, Endothelial Cell; FVIIa, activated factor VII; FX, factor X; FXa, activated FX; MMPs, matrix metalloproteases; NET, Neutrophil Extracellular Trap; NFkB, Nuclear-Factor kappa B; PAR, protease activated receptor; TFPI, Tissue Factor Pathway Inhibitor.