Cc2^−/− mice display larger and more stable thrombi in vivo. (Aa) Z-stack thrombus formation images of FeCl₃-induced vascular injury was monitored in arterioles of wild-type vs Cc2^−/− mice over 10 minutes. The different lengths of time after FeCl₃ application are specified. Note that thrombi are larger in Cc2^−/− arterioles over time compared with wild-type control arterioles (n = 30). (b) Quantitative analysis of arterial thrombogenesis of wild-type (●) vs Cc2^−/− (▪) arterioles. Cc2^−/− arterioles displayed a significantly larger thrombus volume at 10 minutes compared with wild-type arterioles (166 900 ± 7601 vs 120500 ± 2390 µm³; ***P < .0001; n = 30). (c) The kinetics of thrombus volume of wild-type vs Cc2^−/− arterioles over time was reliably measured. Cc2^−/− arterioles were significantly increased at 4 to 10 minutes compared with wild-type arterioles. (d) The thrombus stability was scored from 1 to 10, with 1 being 0% to 10% occupancy and 10 being 91% to 100% occupancy (ie, complete vessel occlusion) visualized over time. Cc2^−/− arterioles showed greater stability in thrombi formed (7.267 ± 0.143 vs 3.493 ± 0.136; ***P < .0001; n = 30). (Ba-b) Platelet thrombus formation in response to laser-induced injury in wild-type, Cc1^−/−, and Cc2^−/− arterioles. Thrombus volume in Cc2^−/− and Cc1^−/− arterioles was significantly greater than wild-type arterioles (37 355 ± 702.6 vs 31 956 ± 785.1 vs 15 578 ± 543.7, respectively; ***P < .0001; n = 30) and displayed greater stability in thrombi formed (5.733 ± 0.143 vs 4.80 ± 0.010 vs 2.967 ± 0.0894, respectively; ***P < .0001; n = 30). (Ca-b) Thrombus formation in response to FeCl₃ after inhibition of mouse GPVI with specific monoclonal antibody (mAb) JAQ1 administration to wild-type and Cc2^−/− mice compared with control IgG-treated wild-type and Cc2^−/− or untreated wild-type and Cc2^−/− mice. Compared with untreated Cc2^−/− or control IgG-treated Cc2^−/− arterioles, JAQ1-treated Cc2^−/− arterioles displayed around a twofold smaller thrombus volume at 10 minutes (154 300 ± 4741 vs 144 600 ± 6613 vs 70 050 ± 5077 µm³, respectively; ***P < .0001; n = 10 arterioles from 3 mice per group) and around a twofold lower stability score at 10 minutes (7.500 ± 0.166 vs 7.400 ± 0.371 vs 4.800 ± 0.359, respectively; ***P < .0001; n = 10 arterioles from 3 mice per group). In contrast, compared with untreated wild-type or control IgG-treated wild-type arterioles, JAQ1-treated wild-type arterioles displayed around a threefold smaller thrombus volume at 10 minutes (118 700 ± 5102 vs 109 800 ± 4497 vs 55 080 ± 5269 µm³, respectively; ***P < .0001; n = 10 arterioles from 3 mice per group) and a moderately lower stability score at 10 minutes (4.100 ± 0.100 vs 4.600 ± 0.163 vs 3.300 ± 0.213, respectively; **P < .01; n = 10 arterioles from 3 mice per group).