Background <p>von Willebrand disease (VWD) is a hereditary bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). Our previous studies demonstrated that emicizumab, a bispecific monoclonal antibody that mimics activated factor VIII (FVIII) cofactor activity, enhances thrombus formation under high-shear conditions in whole blood from patients with VWD (PwVWD). However, its effect on plasma coagulation potential remains unclear.</p> Aim <p>To evaluate the coagulation-enhancing effect of emicizumab in plasma samples from PwVWD using global coagulation assays.</p> Methods <p>Plasma samples from PwVWD (type 1, <i>n</i> = 4; type 2, <i>n</i> = 9; type 3, <i>n</i> = 3) were spiked with emicizumab (50 or 100&#xa0;µg/mL), recombinant VWF (rVWF; 2.4 U/mL), or plasma-derived FVIII/VWF concentrate (pd-FVIII/VWF; 1/2.4 U/mL). Coagulation potential was assessed using clot waveform analysis (Ad|min1|) and thrombin generation assay (Peak-Th).</p> Results <p>Emicizumab dose-dependently increased Ad|min1| in all type 1 VWD samples and improved Peak-Th in two cases. In type 2 VWD, Ad|min1| increased in all samples, while Peak-Th improved in six cases. In type 3 VWD, emicizumab increased both parameters in all cases.</p> Conclusion <p>Emicizumab enhanced ex vivo coagulation potential in plasma samples from PwVWD across all subtypes, supporting its potential as a therapeutic option.</p>

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Emicizumab enhances the ex vivo coagulant potential in plasma samples from patients with von Willebrand disease

  • Mutsumi Yabe,
  • Shoko Furukawa,
  • Masahiro Takeyama,
  • Kana Sasai,
  • Naruto Shimonishi,
  • Yuto Nakajima,
  • Kenichi Ogiwara,
  • Keiji Nogami

摘要

Background

von Willebrand disease (VWD) is a hereditary bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). Our previous studies demonstrated that emicizumab, a bispecific monoclonal antibody that mimics activated factor VIII (FVIII) cofactor activity, enhances thrombus formation under high-shear conditions in whole blood from patients with VWD (PwVWD). However, its effect on plasma coagulation potential remains unclear.

Aim

To evaluate the coagulation-enhancing effect of emicizumab in plasma samples from PwVWD using global coagulation assays.

Methods

Plasma samples from PwVWD (type 1, n = 4; type 2, n = 9; type 3, n = 3) were spiked with emicizumab (50 or 100 µg/mL), recombinant VWF (rVWF; 2.4 U/mL), or plasma-derived FVIII/VWF concentrate (pd-FVIII/VWF; 1/2.4 U/mL). Coagulation potential was assessed using clot waveform analysis (Ad|min1|) and thrombin generation assay (Peak-Th).

Results

Emicizumab dose-dependently increased Ad|min1| in all type 1 VWD samples and improved Peak-Th in two cases. In type 2 VWD, Ad|min1| increased in all samples, while Peak-Th improved in six cases. In type 3 VWD, emicizumab increased both parameters in all cases.

Conclusion

Emicizumab enhanced ex vivo coagulation potential in plasma samples from PwVWD across all subtypes, supporting its potential as a therapeutic option.