Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study.
Marstacimab (PF-06741086)
Rare bleeding disorders
TFPI
Thrombin- generation
Journal
Blood cells, molecules & diseases
ISSN: 1096-0961
Titre abrégé: Blood Cells Mol Dis
Pays: United States
ID NLM: 9509932
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
06
03
2022
revised:
07
04
2022
accepted:
08
04
2022
pubmed:
8
5
2022
medline:
25
5
2022
entrez:
7
5
2022
Statut:
ppublish
Résumé
Rare bleeding disorders (RBD) are inherited coagulopathies, whose hemostatic control is based upon replacement therapy. Marstacimab (PF-06741086) is a human monoclonal IgG that targets the Kunitz2 domain of tissue factor pathway inhibitor [TFPI]. Marstacimab is currently in development for bleeding prophylaxis in patients with hemophilia. To assess the potential impact of Marstacimab upon thrombin generation (TG) in RBD patients' plasma samples. Our cohort included 18 RBD patients, with severe deficiencies: 5 Von Willebrand Disease (VWD) type 3, 4 FVII, 3 FXI, 2 FXIII deficiency and 1 patient with: FX, FV + FVIII, Fibrinogen, combined vitamin K dependent factors' deficiency. Citrated samples from RBD patients were collected and spiked with Marstacimab, TG was measured by calibrated automated thrombogram. Among all patients a reduced baseline TG was observed as compared to controls. Improvement of median (lag time, peak and ETP was observed in Marstacimab spiked samples from 8 min, 99 nM, 1116 nMx min to 5.5 min, 194 nM,1614 nMx min, respectively. None of the values measured among RBD patients exceeded normal controls. These in vitro data suggest that Marstacimab may serve as a promising approach for restoring the hemostatic balance in various RBD, though potential clinical implications should be further investigated.
Sections du résumé
BACKGROUND
Rare bleeding disorders (RBD) are inherited coagulopathies, whose hemostatic control is based upon replacement therapy. Marstacimab (PF-06741086) is a human monoclonal IgG that targets the Kunitz2 domain of tissue factor pathway inhibitor [TFPI]. Marstacimab is currently in development for bleeding prophylaxis in patients with hemophilia.
OBJECTIVES
To assess the potential impact of Marstacimab upon thrombin generation (TG) in RBD patients' plasma samples.
RESULTS
Our cohort included 18 RBD patients, with severe deficiencies: 5 Von Willebrand Disease (VWD) type 3, 4 FVII, 3 FXI, 2 FXIII deficiency and 1 patient with: FX, FV + FVIII, Fibrinogen, combined vitamin K dependent factors' deficiency. Citrated samples from RBD patients were collected and spiked with Marstacimab, TG was measured by calibrated automated thrombogram. Among all patients a reduced baseline TG was observed as compared to controls. Improvement of median (lag time, peak and ETP was observed in Marstacimab spiked samples from 8 min, 99 nM, 1116 nMx min to 5.5 min, 194 nM,1614 nMx min, respectively. None of the values measured among RBD patients exceeded normal controls.
CONCLUSION
These in vitro data suggest that Marstacimab may serve as a promising approach for restoring the hemostatic balance in various RBD, though potential clinical implications should be further investigated.
Identifiants
pubmed: 35525014
pii: S1079-9796(22)00020-1
doi: 10.1016/j.bcmd.2022.102663
pii:
doi:
Substances chimiques
Hemostatics
0
Lipoproteins
0
lipoprotein-associated coagulation inhibitor
0
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102663Informations de copyright
Copyright © 2022. Published by Elsevier Inc.