CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples

Abstract

The hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just prior to and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex-vivo hemostatic activity of rFVIIa and CT-001in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Post-delivery samples were collected 45 (+/-15) mins after delivery. Between the 2 timepoints, soluble fibrin monomer and D-dimer increased while tissue factor, factor VIII, factor V, and fibrinogen decreased. Interestingly, the post-delivery lag time and time-to-peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins post-delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of post-delivery samples in APTT, PT, TGA, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in post-delivery samples and, consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.