Fig. 1.

Initiation and amplification of the coagulation cascade. Initiation (right): upon endothelial damage, subendothelial tissue factor (TF) is exposed to the bloodstreamand binds factor VII, which is activated to factor VIIa. The TF:VIIa complex enables subsequent activation of factor X. Activated factor Xa interacts with factor Va to form the “prothrombinase” complex on the surface of TF bearing cells and converts prothrombin into thrombin. Amplification (right): small amounts of thrombin activate platelets via protease-activated receptors (PARs) and will activate the factor XIa-IXa feedback loop on the surface (PS = phosphatidylserine) of adherent/aggregated platelets. Factor IXa with factor VIIIa forms the “tenase” complex which will then activate additional factor X. Simultaneously, the trace amounts of thrombin will activate factors Xia, VIII(cofactor to factor IX) and V (cofactor to factor X), which dramatically enhances the catalytic activity of factors IX and X. Finally, thrombin (factor IIa) activation leads to fibrin formation within the hemostatic plug which can further be stabilized by thrombin activated factor XIII (not shown). In parallel, local polyphosphate (polyP) release by activated platelets stimulates the contact pathway of coagulation by activation of factor XII. Fig. reproduced with permission from Gaertner, F. and Massberg, S. Blood coagulation in immunothrombosis-At the frontline of intravascular immunity. Semin Immunol. 2016.