TY - JOUR
T1 - Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study
AU - Barg, Assaf A.
AU - Brutman-Barazani, Tami
AU - Avishai, Einat
AU - Budnik, Ivan
AU - Cohen, Omri
AU - Dardik, Rima
AU - Levy-Mendelovich, Sarina
AU - Livnat, Tami
AU - Kenet, Gili
N1 - Publisher Copyright:
© 2022
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - Marstacimab (PF-06741086)
KW - Rare bleeding disorders
KW - TFPI
KW - Thrombin- generation
UR - http://www.scopus.com/inward/record.url?scp=85129282279&partnerID=8YFLogxK
U2 - 10.1016/j.bcmd.2022.102663
DO - 10.1016/j.bcmd.2022.102663
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 35525014
AN - SCOPUS:85129282279
SN - 1079-9796
VL - 95
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
M1 - 102663
ER -
