MAA868 concentration dependently prolongs aPTT and inhibits thrombin generation in human plasma. (A) The concentration-dependent effect of MAA868 on the clotting time of human plasma in the aPTT assay is shown. In the aPTT assay, trigger reagents specific for triggering the intrinsic pathway are used (phospholipid, silicate, and calcium chloride). MAA868 prolongs aPTT clotting times in a concentration-dependent manner (50% inhibitory concentration [IC₅₀] = 13 nM). Doubling of aPTT clotting time was observed at 15 nM. (B) The dose-dependent effect of MAA868 on inhibiting thrombin generation in the TGA is shown. In the TGA, the thrombin→FXIa feedback loop is triggered by low concentrations of tissue factor, and thrombin activity is measured by adding an artificial, fluorogenic substrate to plasma. An IC₅₀ of 24 nM and a residual thrombin concentration of 159 nM, generated by low tissue factor concentration, were calculated for MAA868. The residual thrombin concentration in this assay is likely due to thrombin generation induced by small amounts of tissue factor.