Initiation of coagulation by tissue factor carriers in blood

Abstract

Fibrin can be generated in blood vessels in the absence of substantial damage to the vessel wall. According to novel observations, fibrin formation within the vessel lumen could be initiated by intravascular (blood borne) tissue factor (TF), a central starter protein of blood coagulation. We have recently detected TF in platelets, principally allowing coagulation to be initiated within the developing thrombus. While TF is stored in intraplatelet compartments under resting conditions, it is rapidly translocated to the cell surface in response to platelet activation, accumulating on filopodia. Platelet TF might be acquired from extracellular sources via transfer of TF positive microparticles and/or, potentially, be generated through translational mechanisms. Exocytotic microparticles, regular blood components, share the ability of the activated platelets to coexpose TF and phosphatidylserine, allowing the assembly of the entire coagulation system on a single membrane surface. Nonetheless, the procoagulant activity of the microparticles, when present alone, is limited. However, the vesicular TF might be uncovered by platelet-microparticle interactions. Thereby, the recruitment of platelets and microparticles to the site of vascular injury could synergistically trigger fibrin generation. In summary, by utilizing differential pathways, activated platelets are mandatory for the TF-mediated coagulation start in blood.