PB1145 - Coagulation assays for assessing direct Factor Xa inhibitor oral anticoagulant reversal effects

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Magdolna Nagy, PhD

Postdoctoral Researcher
Coagulation Profile, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

TG

Tainá Gomes

R&D Scientist
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Rv

René van Oerle

Chief Operating Officer
Coagulation Profile, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
TH

Tilman M. Hackeng, PhD

Chief Scientific Officer
Coagulation Profile, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
PR

Pieter Reitsma

Chief Scientific officer
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Gerard Short, MRCP FFPM MBA

Chief Medical Officer
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
HS

Henri M.H. Spronk

Chief Executive Officer
Coagulation Profile, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
DV

Daniël Verhoef

Director of Research
VarmX, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands

Background: Factor Xa direct oral anticoagulants (FXa-DOACs) require rapid reversal in patients with serious bleeding or prior to urgent surgery. VMX-C001 is a recombinant variant of human FX under clinical development as a FXa-DOAC bypassing agent. Because standard laboratory coagulation tests lack sensitivity to assess the effects of FXa-DOAC, two commercially-available coagulation assays, dilute Russell’s viper venom time (dRVVT) and dilute prothrombin time (dPT), were modified to develop more sensitive assays.

Aims: To evaluate the modified dRVVT and dPT assays and their sensitivity to FXa-DOACs.

Methods: Citrated platelet-poor plasma samples were obtained from healthy volunteers (n=22). Assay validity was measured in 3x and 4x diluted plasma for dRVVT and in undiluted and 2.5x diluted plasma for dPT in the absence and presence of apixaban (100 or 250 ng/mL) and/or VMX-C001 (30 μg/mL; approximately 0.3 U/mL). Plasma samples from healthy volunteers were then spiked ex vivo with apixaban (n=22), edoxaban (n=3), or rivaroxaban (n=3) at 0‒400 ng/mL with and without VMX-C001 (0.3 U/mL) and dRVVT and dPT were measured. In vivo assay validation was performed using plasma samples taken from healthy volunteers who had received apixaban (n=8) or rivaroxaban (n=5) for 3.5 days before measuring dRVVT and dPT in samples taken before and after the FXa-DOAC dose on day 4.

Results: Both assays were validated and sensitive to FXa-DOACs, resulting in dose-dependent prolongation of dRVVT and dPT, which was reversed when VMX-C001 was present in plasma, resulting in normal dRVVT and dPT (Figure 1). Assay validity was also confirmed with the plasma samples taken from subjects treated with FXa-DOACs in vivo (Figure 2).

Conclusion(s): dRVVT and dPT assays can be used to monitor FXa-DOAC anticoagulation with a high degree of sensitivity and can serve as surrogate endpoints in studies of the FXa-DOAC reversal agent VMX-C001.