Influence of inhibitory titer on residual fVIII activity and peak thrombin generation.

<p>The inhibitor titer for each MAb was compared with the peak thrombin generation of fVIII alone or fVIII + rfVIIa at the immediate (solid circles, r² = 0.36) or 1 hr (open circles, r² = 0.09) time points (A.) and with residual fVIII activity at the immediate (solid circles, r² = 0.004) or 1 hr (r² = 0.07) time points (B.).</p

Amount of fVIII needed to restore thrombin generation of rfVIIa.

<p>Varying concentrations of fVIII were mixed 1∶1 with rfVIIa at a final concentration of 2.25 µg/ml to determine the level of fVIII activity necessary for restoration of thrombin generation of rfVIIa to fVIII at 1 U/ml. The resulting data was transformed using manufacturer’s software to yield thrombin generation curves (A), peak thrombin concentration (B) and index velocity (C). Error bars represent sample standard deviation.</p

Epitope map of non-overlapping MAbs.

<p>The relative epitopes of anti-fVIII MAbs are shown. MAbs 4A4, 2–54, 1D4 and 2–93 target non-overlapping epitopes in the A2 domain. MAbs G38 and 2–113 target non-overlapping epitopes in the A3 domain at residues 1690–1817 and 1818–1916, respectively. MAbs I109 and 2–77 target non-overlapping epitopes in the C2 domain. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048172#pone.0048172-Meeks1" target="_blank">[13]</a>.</p

Characteristics of anti-fVIII MAbs.

<p>Characteristics of anti-fVIII MAbs.</p

TGA parameters for anti-fVIII MAbs.

<p>ETP, peak thrombin and index velocity are presented as ratios compared to fVIII deficient plasma supplemented with 1 U/ml fVIII in the absence of any anti-fVIII MAb.</p><p>ETP – endogenous thrombin potential.</p

Inhibition of thrombin generation by group 1 anti-fVIII MAbs.

<p>Thrombin generation curves are shown for fVIII deficient plasma (negative control), fVIII deficient plasma with 1 U/ml of fVIII (positive control) and 1 U/ml of fVIII in the presence of 5 µg/ml of specified group 1 MAb. Data represent mean ± sample standard deviation for 3 experiments where duplicates of each measurement were taken and averaged.</p