Antithrombotic and anticoagulant activity of MAA868 in FXI^−/− mice reconstituted with hFXI. A total of 0.6 mg/kg hFXI was administered IV to FXI^−/− mice followed by IV administration of vehicle, an isotype control IgG, MAA868, or DEF. Thrombosis was induced 20 minutes later by applying 5% FeCl₃ to the surface of the carotid artery, and blood flow was monitored for 30 minutes thereafter. Blood was collected from the vena cava, and plasma was prepared for aPTT analysis as well as for FXI_f and antibody measurements. (A) Antithrombotic activity is shown for antibodies injected at the indicated molar ratios of hFXI and was assessed by measuring carotid blood flow (inversely related to extent of vessel occlusion) over 30 minutes. Antithrombotic activity (%) = (mean blood flow during the thrombogenic period)/(baseline blood flow) × 100. (B) Anticoagulant activity of antibodies as assessed by aPTT measurement and is shown as % of maximum aPTT observed in FXI^−/− not reconstituted with hFXI. (C) Free total hFXI plasma levels (including free hFXIa) are shown. (D) Total monoclonal antibody (mAb) plasma levels measured during the study. Values for each group are shown as means ± standard error of the mean. *P < .05 vs hFXI, **P < .01 vs hFXI.