Page 127 - Haematologica Vol. 107 - September 2022

ARTICLE - Effects of BT200 on VWF/FVIII in humans K.D. Kovacevic et al.
doubling of FVIII was already seen in some individuals after a single 6 mg dose. Increased FVIII levels were re- flected by a reciprocal shortening of the activated partial thromboplastin time (P<0.001) (Online Supplementary Figure S8), and an up to 2-fold increase in peak thrombin generation (P<0.001) (Online Supplementary Figure S9). To investigate the potential mechanism of action for the
increased VWF/FVIII levels, we considered that increased VWF secretion might contribute to the VWF elevation and therefore measured VWF propeptide levels. However, BT200 did not raise VWF propeptide levels (Online Sup- plementary Figure S10), resulting in a 4-fold lower VWF propeptide/antigen ratio and demonstrating that BT200 does not increase VWF secretion or release.
Figure 2. Free von Willebrand factor A1-domains (%) after single doses of BT200, measured by enzyme-linked immunosorbent assay. Data are mean values without error bars for better visibility (n=6 for BT200 groups, n=20 for placebo). VWF: von Willebrand factor; sc: subcutaneous; inj: injection; inf: infusion.
Figure 3. Plasma levels of von Willebrand factor antigen (%) after single doses of BT200. Data are mean values without error bars for better visibility (n=6 for BT200 groups, n=20 for placebo). VWF: von Willebrand factor; sc: subcutaneous; inj: injection; inf: infusion.
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