Anti-TFPI for hemostasis induction in patients with rare bleeding disorders, an ex vivo thrombin generation (TG) guided pilot study

Assaf A. Barg, Tami Brutman-Barazani, Einat Avishai, Ivan Budnik, Omri Cohen, Rima Dardik, Sarina Levy-Mendelovich, Tami Livnat, Gili Kenet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number102663
JournalBlood Cells, Molecules, and Diseases
Volume95
DOIs
StatePublished - Jul 2022

Keywords

  • Marstacimab (PF-06741086)
  • Rare bleeding disorders
  • TFPI
  • Thrombin- generation

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