Figure 2

Coagulation pathways implicated in intrinsic (contact activation, CA) - and extrinsic (tissue factor, TF) based global assays with highlighted targets for oral anticoagulation. Cofactors V and VIII are indicated in their activated forms. Grey squares indicate vitamin K-dependent procoagulant factors, targets for VKA anticoagulation. Black circles indicate the target for direct factor Xa inhibitors, i.e. rivaroxaban and apixaban. Black triangle shows the target for the direct thrombin inhibitor dabigatran. Specificity and sensitivity of extrinsic pathway based assays is determined by the tissue factor (TF) concentration. At high TF concentrations, enough factor X is activated directly by TF/VIIa and hence the contribution of factor IX and factor VIII is negligible. At low TF concentrations (<5 pM), extrinsic based assays are also sensitive to factor VIII and IX. Dotted arrowed line indicates feedback activation of factor XI by thrombin (IIa), allowing factor XI to be involved in the extrinsic pathway but this is noticed only at very low tissue factor concentration (≤1 pM). Θ, negatively charged surface, e.g. celite or kaolin, facilitating contact activation. Fbg, fibrinogen. Fb, fibrin.