The vast majority of the TF expressed on the surfaces of resting cells is maintained in a cryptic, coagulant-inactive state (Schecter AD et al. 1997; Bach RR 2006; Kothari H et al. 2013; Grover SP & Mackman N 2018). This cryptic TF can bind to FVIIa, but the formed TF:FVIIa complex fails to activate FIX and FX (Rao LV & Pendurthi UR 2012). Upon tissue injury or inflammation TF is converted into its procoagulant isoform at the cell surface. Several mechanisms have been proposed for TF activation or decryption. These include Ca²⁺-dependent exposure of phosphatidylserine (PS) on the outer plasma membrane as a result of reduced lipid flippase activity, protein disulfide isomerase (PDI)-mediated thiol-disulfide exchange reaction that affects the allosteric disulfide bond in TF (Rao LV & Pendurthi UR 2012; Grover SP & Mackman N 2018; Ansari SA et al. 2019). In addition, the presence of sphingomyelin (SM) in the outer leaflet of the plasma membrane inhibits TF procoagulant activity on the cell surface of resting cells (Wang J et al. 2017). Acid-sphingomyelinase (ASM)-mediated hydrolysis of SM removes the inhibitory effect of SM on TF activity, thus leading to TF decryption (Wang J, et al. 2017; Ansari SA et al. 2019). It has been suggested that SM hydrolysis, PS externalization and thiol-disulphide exchange pathways synergistically contribute to the activation of TF (Langer F & Ruf W 2014; Ansari SA et al. 2019).

The Reactome event describes exposure of TF sequestered in the wall of a blood vessel to flowing blood.