PB0832 - Optimizing treatment of pregnant women with von Willebrand disease: a retrospective analysis of factor replacement therapy during delivery

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Wala Al Arashi, MD

PhD candidate
Erasmus MC, University Medical Center Rotterdam
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

MC

Michael E. Cloesmeijer

MSc, PhD candidate
Department of Hospital Pharmacy & Clinical Pharmacology, Amsterdam UMC – location AMC, The Netherlands.
Amsterdam, Noord-Holland, Netherlands
Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
MK

Marieke J.H.A. Kruip

Associate professor, hematologist, MD, PhD
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
RM

Ron A.A. Mathôt

Professor, Clinical pharmacologist, PharmD, PhD
Department of Hospital Pharmacy & Clinical Pharmacology, Amsterdam UMC – location AMC, The Netherlands.
Amsterdam, Noord-Holland, Netherlands
MC

Marjon H. Cnossen

Associate professor, pediatric hematologist, MD, PhD
Department of Pediatric Hematology, Erasmus MC – Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Von Willebrand factor containing concentrates are used to prevent or treat postpartum hemorrhage in pregnant women with Willebrand disease (VWD). Limited data are available on VWF activity (VWF:Act) and factor VIII (FVIII:C) levels during delivery after administration of VWF/FVIII concentrate.

Aims: The aim of this study was to evaluate treatment with VWF/FVIII concentrate (Haemate®P) in women with VWD during delivery and postpartum period.

Methods: In this retrospective single center study, data were collected between January 1st 2008 and August 1st 2022 from pregnant women who were treated with Haemate®P during delivery and who had at least two VWF:Act/FVIII:C measurements during treatment. VWF-Act/FVIII:C were compared to predefined factor levels according to guidelines with target VWF:Act/FVIII:C peak >1.0 IU/ml (before 2020) and >1.5 IU/ml (after 2020) at delivery. Haemate®P dose was calculated based on third trimester factor levels. Subsequently, observed VWF:Act/FVIII:C were predicted by a population pharmacokinetic (PopPK) model for non-pregnant individuals developed by Bukkems (2021).

Results: Nineteen women were included (Table 1). All patients were treated prophylactically. Overall, target VWF:Act/FVIII:C peak were achieved within ≤24 hours after treatment and all VWF:Act/FVIII:C trough reached above ≥0.5 IU/mL within 72 hours of treatment (Figure 1). In all women pretreatment FVIII:C was above ≥1.0 IU/mL (excluding VWD type 2N) and was significantly higher compared to third trimester levels (increase of 0.42 [0.12-0.92]; median [25%,75%]). Trough levels of FVIII:C were high (2.05 [1.65-2.71]; median [25%,75%]). The PopPK model adequately predicted VWF:Act, but not FVIII.

Conclusion(s): Targeted VWF:Act/FVIII:C peak levels were achieved with chosen dosing regimens and the pharmacokinetics of VWF seem to be similar as in non-pregnant individuals. However, high pretreatment and consequently high trough FVIII:C were observed, suggesting the need to further investigate required FVIII:C levels in pregnancy and to personalize dosing regimens and to establish best practice with regard to type of VWF/FVIII concentrates.