PB0642 - Determinants of the bleeding phenotype in persons with non-severe hemophilia

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

FK

Fabienne R. Kloosterman, MD

PhD candidate
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology, Meibergdreef 9, Amsterdam, Netherlands
Utrecht, Utrecht, Netherlands

Co-Author(s)

AZ

Anne-Fleur Zwagemaker

PhD candidate
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology, Meibergdreef 9, Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
Catherine N. N. Bagot, Dr MBBS MD

MD, PhD
Department of Haematology, Glasgow Royal Infirmary, Glasgow, United Kingdom
Glasgow, Scotland, United Kingdom
EB

Erik A.M. Beckers

Head of Haematology
Department of Hematology, Maastricht University Medical Center + and Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
SB

Sara Boyce

MD, PhD
Department of Haematology, University Hospital Southampton, Southampton, United Kingdom
Southampton, England, United Kingdom
PB

Paul Brons

Dr.
Department of Pediatric Hemato-Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
Giancarlo Castaman, MD

Medical Director
Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
Peter W. Collins, MD

Professor of Haematology
Arthur Bloom Haemophilia Centre, School of Medicine, Cardiff University Hospital, Cardiff, United Kingdom
Cardiff, Wales, United Kingdom
Jeroen C.J Eikenboom, MD. PhD

Professor, Head of Division of Thrombosis and Hemostasis
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
CH

Charles Hay

Clinical Professor of Haemostasis and Thrombosis, Consultant Haematologist
University Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom
Manchester, England, United Kingdom
Shannon Jackson, MD (she/her/hers)

Hematologist, Providence Health Care
Providence Hematology, St. Paul’s Hospital, Vancouver, BC, Canada
Vancouver, British Columbia, Canada
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
Christoph Male, MD, MSc

Head of the Pediatric Hemostasis & Thrombosis Unit
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Vienna, Wien, Austria
Karina Meijer, MD, PhD (she/her/hers)

MD, PhD, Internist-haematologist, Professor
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Groningen, Groningen, Netherlands
LN

Laurens Nieuwenhuizen

Internist-hematologist
Hemophilia Treatment Center Nijmegen – Eindhoven – Maastricht, The Netherlands. Department of Hematology, Maxima Medical Center, Eindhoven, The Netherlands.
Eindhoven, Noord-Brabant, Netherlands
Susan Shapiro, MD, PhD (she/her/hers)

Consultant Hematologist
Oxford University Hospitals National Health Service Foundation Trust, Oxford, UK
Oxford, England, United Kingdom
Michiel Coppens, MD, PhD (he/him/his)

Medical Specialist
Amsterdam University Medical Centers, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
KF

Karin Fijnvandraat

Professor
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands

Presenting Author(s)

Samantha Gouw, MD, PhD (she/her/hers)

Pediatric Hematologist
The University of Amsterdam
Amsterdam, Noord-Holland, Netherlands

Background: In non-severe hemophilia, baseline factor VIII/IX level is the major determinant of the bleeding phenotype. Yet, knowledge on other patient-specific and environmental determinants of the bleeding phenotype may contribute to further understanding of individuals’ bleeding risk and provide targets for optimization of their treatment.

Aims: We aim to identify potential determinants of bleeding phenotype other than the factor VIII/IX level in persons with non-severe hemophilia.

Methods: The DYNAMO study (international multicenter cohort) included persons with non-severe hemophilia (FVIII/IX 2-35 IU/dL) aged 12-55 years. The primary outcome was annualized joint bleeding rate (AJBR). Data on the following determinants was collected: hemophilia type (A/B), blood group, von Willebrand factor activity (VWF) level, desmopressin response, BMI, factor V Leiden and prothrombin G20210A mutation. Associations between the determinants and joint bleeding rate was assessed by a frailty model for recurrent events and expressed as (adjusted) hazard ratios (aHR). Associations were adjusted for factor VIII/IX levels. Medical ethics approval and written consent was obtained (ClinicalTrials.gov Identifier: NCT03623295).

Results: In total, 304 persons were included with a median age of 38 years (IQR 25-49) and a median FVIII/IX level of 12 IU/dL (IQR 5-21). The median AJBR was 0.0 (IQR 0.0-0.2). There was a trend found between higher VWF levels and a decrease in AJBR (aHRs 0.61 (95% confidence interval 0.27-1.41) for vWF 100-150 IU/dL and 0.24 (95%CI 0.04-1.29) for vWF >150 IU/dL, compared to 50-100 IU/dL). No clear associations were seen between the other studied determinants and the AJBR were found (Table 1).

Conclusion(s): In our study in persons with non-severe hemophilia, AJBR slightly decreased with increasing VWF levels, but confidence intervals were wide.