Effects of caplacizumab, a specific inhibitor of the A1 domain of von Willebrand factor binding with platelet membrane glycoprotein (GP) Ibα, on the length of platelet pseudopods supporting platelet adhesions on immobilized von Willebrand factor under blood flow condition

Abstract

A1 domain of von Willebrand factor (VWF) binding with platelet glycoprotein (GP) Ibα play crucial roles in platelet adhesion and subsequent passive shape changes in the platelets such as pseudopod formation under high wall shear rate conditions. However, the effects of specific inhibitors of VWF binding with GPIbα on the length of pseudopods supporting platelet adhesion on VWF are still to be elucidated. Here we measured the length of pseudopods in the presence of VWF-GPIbα inhibitor of caplacizumab. The length of pseudopods was 6.5 ± 0.2 μm (mean ± 95% confidential interval [CI]) and 6.9 ± 0.2 μm (mean ± 95% CI) at 100 and 200 nM of caplacizumab concentrations and was longer than those formed in its absence (5.2 ± 0.2 μm, p < 0.05). Our experiments also revealed that the surface area coverage by platelets in the presence of caplacizumab at a concentration of 200 nM of 26.1 ± 6.4% after 60-second blood perfusion was smaller than its absence (45.2 ± 7.5%, p < 0.05). Our results suggest that fewer numbers of VWF-GPIbα bonds generating larger binding force with a longer length of pseudopods, support the platelet adhesion on VWF in the presence of caplacizumab at a wall shear rate of 1,500 s -1 .