OC 63.4 - Little discrepancy of one-stage and chromogenic assays in a large international cohort of patients with non-severe hemophilia A and B (DYNAMO study)

Tuesday, July 12, 2022

3:30 PM – 3:45 PM

Location: ExCel Center, ICC Capital Suite Room 7&12

Presentation Format: In-Person

Co-Author(s)

AZ

Anne-Fleur Zwagemaker

PhD student
Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
FK

Fabienne Kloosterman

PhD student
Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
SG

Samantha C. Gouw, MD, PhD

Pediatric Hematologist
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology, Meibergdreef 9, Amsterdam, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Amsterdam, Noord-Holland, Netherlands
SB

Sara Boyce

Hematologist
Department of Haematology, University Hospital Southampton, Southampton, United Kingdom
Southampton, England, United Kingdom
PB

Paul Brons

Pediatric hematologist
Department of Pediatric Hemato-Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
Nijmegen, Gelderland, 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
Peter W. Collins, MD

Professor of Haematology
Arthur Bloom Haemophilia Centre, School of Medicine, Cardiff University Hospital, Cardiff, United Kingdom
Cardiff, Wales, United Kingdom
JE

Jeroen C.J. Eikenboom

Professor, Internist, Head of Div. T&H
Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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
SJ

Shannon Jackson

Hematologist
Adult Bleeding Disorders Program of BC - Adult Division St. Paul's Hospital, Vancouver, British Columbia, Canada
Vancouver, British Columbia, Canada
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
BL

Britta Laros-van Gorkom

Hematologist
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, The Netherlands
Nijmegen, Gelderland, Netherlands
Christoph Male, MD, MSc

Head of the Pediatric Hemostasis & Thrombosis Unit
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Vienna, Wien, Austria
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

Consultant Hematologist
Oxford University Hospitals National Health Service Foundation Trust, Oxford, UK
Oxford, England, United Kingdom
KF

Karin Fijnvandraat

Professor of Pediatric Hematology
Department of Pediatric Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands

Presenting Author(s)

Michiel Coppens, MD, PhD

Medical Specialist
Department of Vascular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands

Background: Measurements of coagulation factor activity are essential for hemophilia management and are generally performed with the one-stage or chromogenic assay. Currently it is suggested that around one-third of patients with non-severe hemophilia A have assay discrepancy. These data are limited for non-severe hemophilia B. Knowledge on the extent of assay discrepancy in perspective of previous literature may facilitate further interpretation of this phenomenon.

Aims: To investigate the extent of assay discrepancy in moderate and mild hemophilia A and B.

Methods: Patients with non-severe hemophilia A and B were included from the multicenter international DYNAMO study. Central measurements of FVIII and FIX activity levels were performed by the one-stage (Actin FS reagents) and chromogenic assay (FVIII Siemens, FIX Rossix). Assay discrepancy was defined as a ratio >2.0 or < 0.5 between the assay results according to the SSC ISTH. Ethics approval and written consent was obtained (ClinicalTrials.gov: NCT03623295).

Results: A total of 221 patients were included of whom 4 patients (2%) showed assay discrepancy. This corresponded to 2/175 hemophilia A patients and 2/46 hemophilia B patients. Another 4 patients did not meet the criteria but exhibited a potential clinically relevant absolute difference >10 IU/dL between the assay results. The median difference between the assays was generally low with 1.1 IU/dL (IQR 0.5-2.1) for the total cohort, 1.0 IU/dL (IQR 0.4-1.9) in case of higher one-stage results and 1.3 IU/dL (IQR 0.7-2.4) in case of higher chromogenic results (Figure 1). Thirteen patients in this cohort had a F8/F9 mutation associated with assay discrepancy in at least 3 patients in previous literature. Most of these patients (92%) had no discrepant results in our study.

Conclusion(s): Little assay discrepancy was observed, even in those persons with mutations previously associated with discrepancy. This suggests that the previously reported discrepancy could be more dependent on laboratory- than on patient-related factors.