Treatment with factor VIIa increases circulating extracellular vesicles from the endothelium in patients with hemophilia, according to a new study published in the Journal of Thrombosis and Haemostasis. The authors of the study also showed, using ex vivo experiments, that factor VIIa-released extracellular vesicles promote the activation of factor X.
These findings raise the possibility that factor VIIa-released extracellular vesicles may contribute to the hemostatic effect of recombinant factor VIIa. They may also explain why treatment with recombinant factor VIIa is ineffective in some patients with hemophilia. This knowledge could influence the dosing schedule of the treatment.
Although most research suggests that the hemostatic response induced by factor VIIa is dependent on platelets, recombinant factor VIIa has also been successfully used to treat patients with platelet disorders.
Read more about the etiology of hemophilia
Here, a team of researchers led by L. Vijaya Mohan Rao, PhD, from the Department of Cellular and Molecular Biology at the University of Texas Health Science Center at Tyler in Texas analyzed plasma samples from 10 patients with severe hemophilia who were treated with recombinant factor VIIa.
They found that the number of extracellular vesicles was markedly higher in the plasma of patients treated with factor VIIa than in preinfusion plasma samples or plasma samples obtained from healthy volunteers. There was no such increase in the number of extracellular vesicles in the plasma of patients with hemophilia who were treated with factor VIII. The researchers concluded that treatment with factor VIIa induces the release of extracellular vesicles.
More research is now needed on the potential of factor VIIa-released extracellular vesicles in the treatment of other bleeding disorders and the off-label use of recombinant factor VIIa.
Factor VII is one of the proteins produced by the liver that is essential for the coagulation cascade. Factor VIIa is a synthetic form of naturally occurring factor VII protein.
Das K, Pendurthi UR, Manco-Johnson M, Martin EJ, Brophy DF, Rao LVM. Factor VIIa treatment increases circulating extracellular vesicles in hemophilia patients: implications for the therapeutic hemostatic effect of FVIIa. J Thromb Haemost. Published online May 24, 2022. doi:10.1111/jth.15768