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CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples.
Sim, Derek S; Mallari, Cornell R; Hermiston, Terry W; Bae, Daekyeong; Lee, Sul; Allen, Terrence; Gilner, Jennifer; Kim, Seung-Chul; James, Andra H.
Afiliación
  • Sim DS; Coagulant Therapeutics, Berkeley, CA.
  • Mallari CR; Coagulant Therapeutics, Berkeley, CA.
  • Hermiston TW; Coagulant Therapeutics, Berkeley, CA.
  • Bae D; Coagulant Therapeutics, Seoul, Republic of Korea.
  • Lee S; Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Republic of Korea.
  • Allen T; Department of Anesthesiology, Duke University, Durham, NC.
  • Gilner J; Department of Obstetrics and Gynecology, Duke University, Durham, NC.
  • Kim SC; Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Republic of Korea.
  • James AH; Department of Obstetrics and Gynecology, Duke University, Durham, NC.
Blood Adv ; 8(2): 287-295, 2024 01 23.
Article en En | MEDLINE | ID: mdl-38039512
ABSTRACT: The hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before 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-001 in 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. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery 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 after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, 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 postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemostáticos / Hemorragia Posparto Límite: Female / Humans / Pregnancy Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemostáticos / Hemorragia Posparto Límite: Female / Humans / Pregnancy Idioma: En Revista: Blood Adv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos