PB0273 - von Willebrand factor pharmacokinetics model : real-life surgery data from the WILL-PK study

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

MD

Melanie Daniel

MD, Fellow
Inserm U1011-EGID, Lille Pasteur Institute, Lille University Hospital
Lille, Nord-Pas-de-Calais, France

Co-Author(s)

CP

Camille Paris

MD
Hematology and Transfusion, Lille University Hospital
Lille, Nord-Pas-de-Calais, France
EJ

Emmanuelle Jeanpierre

PharmD
CHU Lille, Service d'Hemostase et Transfusion - Lille FRANCE
Lille, Nord-Pas-de-Calais, France
BP

Bénédicte Pradines

Research assistant
Hematology and Transfusion, Lille University Hospital
Lille, Nord-Pas-de-Calais, France
AR

Antoine Rauch

MD, Professor of Hematology
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
JG

Jenny Goudemand

MD, Professor of Hematology
Hematology and Transfusion, Lille University Hospital
Lille, Nord-Pas-de-Calais, France
Peter J. Lenting, PhD

Researcher
INSERM U1176, Université Paris Saclay, Le Kremlin-Bicêtre, France
Le Kremlin-Bicêtre, Ile-de-France, France
SS

Sophie Susen, PhD,MD

Professor of Haematology
Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France
Lille, Nord-Pas-de-Calais, France
XD

Xavier Delavenne

PharmD, Professor of Pharmacology
Inserm, SAINBIOSE U1059, Saint-Etienne University Hospital
Saint-Etienne, Rhone-Alpes, France

Background: Patients with von Willebrand disease (VWD) can require peri-operative treatment with von Willebrand factor (VWF) concentrate with/without factor VIII (FVIII). Some studies have evaluated the relationship between VWF and FVIII pharmacokinetics (PK) after VWF concentrates containing FVIII. However, there are no data on plasma-derived VWF (pdVWF) without FVIII such as Wilfactin/Wilfact® (LFB, France).

Aims: Develop a joint PK population model for pure VWF concentrate use in patients undergoing surgery, tailored to VWD type and severity.

Methods: Patients treated perioperatively with pure pdVWF from 2016 to 2018 were used to develop a population PK model. Data were analyzed using the nonlinear mixed-effects modeling software Monolix. The model comprised two compartments representing plasma VWF:Ag and FVIII:C. An indirect PK model was used to capture the relationship between VWF:Ag and FVIII:C. A linear relationship was used for the VWF:Ag and VWF:Act relationship. Covariates included in the model are described in Table 1.

Results: A total of 359 VWF:Ag, 359 VWF:Act and 351 FVIII:C measurements from 74 patients (99 surgeries) were included (see Table 1). The mean VWF baseline, clearance, volume of distribution were 0.75 UI.mL-1 (VWD2N as reference), 66 mL.h-1, 4507 mL, respectively. The mean FVIII:C baseline, clearance, volume of distribution were 0.58 UI.mL-1 (VWD2N as reference), 601 mL.h-1, 4179 mL respectively. The level of VWF:Ag inhibiting 50% of FVIII clearance was 1.12 IU.mL -1. The covariates that significantly affect the PK of VWF and FVIII were bodyweight, VWD type, blood group, VWF:pp, and age. Interindividual variability of PK parameters varied from 25.3 to 73.8%.

Conclusion(s): We identified a large PK variability of VWF/FVIII post-infusion of pure VWF concentrates. However, several covariates have been identified to significantly affect interindividual PK variability. Taking those into account could help optimize treatment of VWD patients in surgical context.