PB0281 - Baseline coagulation factor levels determine desmopressin response in bleeding disorders: a systematic review and meta-analysis

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

SL

Sebastiaan Laan

PhD student
Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
Jd

Jessica del Castillo-Alferez

Msc.
Department of Molecular Hemostasis, Sanquin Research, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Suzanne C. Cannegieter

MD, PhD, prof
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands
KF

Karin Fijnvandraat

Professor
Emma Kinderziekenhuis/AMC, University of Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
MK

Marieke J.H.A. Kruip

Hematologist
Department of Hematology, Erasmus MC, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
SL

Saskia Le Cessie

Professor
Department of Clinical Epidemiology – LUMC – Netherlands & Department of biomedical data sciences – LUMC - Netherlands
Leiden, Zuid-Holland, Netherlands

Presenting Author(s)

Ruben Bierings, PhD

Associate Professor
Hematology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

Jeroen Eikenboom

MD, PhD, prof
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
Iris van Moort

Postdoctoral researcher
Erasmus MC University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Several bleeding disorders can be treated with desmopressin to prevent or stop bleeding. However, large inter-individual variability is observed in desmopressin response and the determinants of response are largely unknown.

Aims: In this systematic review we aim to identify the factors that determine desmopressin response in patients.

Methods: A literature search was performed to include papers until December 2022 of patients with various bleeding disorders receiving desmopressin. VWF Antigen (VWF:Ag) and/or Factor VIII (FVIII:C) in IU/dL levels 1 hour after administration were used to define complete (>50), partial (>30, < 50) and non ( < 30) responders. We determined if disease type, weight, age, sex, blood group, VWF or F8 mutations, and baseline coagulation factor levels were possible determinants. Risk of bias was assessed using an adjusted QUIPS checklist.

Results: In total, 104 studies were included with 1826 patients. Desmopressin response varied between disease subtypes(Figure 1). For hemophilia A (HA), the proportion of complete responders increased with increasing baseline FVIII:C and age(Figure 2). One IU/dL increase in FVIII:C baseline resulted in 5.4% higher odds of having a complete desmopressin response (OR=1.054, 95%CI 1.013–1.100). One year increase in age also showed a 5.5% higher odds (OR=1.055, 95%CI 0.96–1.15). For von Willebrand disease (VWD) type 1, VWF:Ag (OR=1.044, 95%CI 1.014–1.074) and VWF activity (OR=1.046, 95%CI 1.031–1.079) determined the odds of a complete response and so did age (OR=1.014, 95%CI 0.948–1.085). For 396 HA patients, 165 F8 mutations, and for 371 VWD patients 85 VWF mutations were investigated. A large variation in response was observed within specific mutations or VWF/FVIII domains, highlighting that other factors than mutation determine desmopressin response.

Conclusion(s): Response to desmopressin varies between disease subtypes, and was largely determined by the baseline levels of FVIII:C and VWF:Ag, although age also had a significant influence on response.

Funding: Netherlands Organization for Scientific Research(NWA.1160.18.038).