Figure 7.
Figure 7. Antithrombotic activity of hTM/R6.5 is largely reversed by APC inhibition. (A) Design of APC inhibition experiments. Anti-hAPC antibody (HAPC1573) or equimolar isotype control were mixed into WB at 300 nM concentration. (B) Inhibition of APC significantly reduced the antithrombotic effect of hTM/R6.5 while not significantly affecting fibrin deposition in endothelialized channels not treated with fusion protein. Graph shows mean ± SEM, with n = 2 channels for each condition. (C) AUC analysis. *P < .05 vs all other conditions; #, not significant (P = .47); ##, not significant (P = .72). (D) Time curves of the first derivative of fibrin fluorescence intensity demonstrate the effects of various combinations of HAPC1573 and hTM/R6.5 on key parameters (described in supplemental Figure 4): peak fibrin generation rate and time to peak fibrin generation rate. Dotted lines show actual values, whereas solid lines show Gaussian functions fitted to these data. Parameters and their 95% confidence intervals are shown in supplemental Table 10.

Antithrombotic activity of hTM/R6.5 is largely reversed by APC inhibition. (A) Design of APC inhibition experiments. Anti-hAPC antibody (HAPC1573) or equimolar isotype control were mixed into WB at 300 nM concentration. (B) Inhibition of APC significantly reduced the antithrombotic effect of hTM/R6.5 while not significantly affecting fibrin deposition in endothelialized channels not treated with fusion protein. Graph shows mean ± SEM, with n = 2 channels for each condition. (C) AUC analysis. *P < .05 vs all other conditions; #, not significant (P = .47); ##, not significant (P = .72). (D) Time curves of the first derivative of fibrin fluorescence intensity demonstrate the effects of various combinations of HAPC1573 and hTM/R6.5 on key parameters (described in supplemental Figure 4): peak fibrin generation rate and time to peak fibrin generation rate. Dotted lines show actual values, whereas solid lines show Gaussian functions fitted to these data. Parameters and their 95% confidence intervals are shown in supplemental Table 10.

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