OC 63.1 - Decreased thrombin generation profile is associated with severe bleeding phenotype in hemophilia: data from the Hemophilia in the Netherlands study

Tuesday, July 12, 2022

2:45 PM – 3:00 PM

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

Presentation Format: In-Person

Presenting Author(s)

Marieke Verhagen, MD

PhD student, MD
Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands. Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, the Netherlands. Laboratory of hematology, Radboud university medical center, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands

Co-Author(s)

Wv

Waander L. van Heerde

Biochemist, Coagulation Physiologist, Chief Scientific Officer Enzyre BV
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands. Hemophilia Treatment Center Nijmegen – Eindhoven – Maastricht, The Netherlands. Enzyre BV, Novio Tech Campus, Nijmegen, The Netherlands.
Nijmegen, Gelderland, Netherlands
JB

Johanna G. Bom, van der

professor of Clinical Epidemiology
Department Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
EB

Erik A.M. Beckers

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

Nicole M.A. Blijlevens

Internist-hematologist, Professor
Department of Hematology, Radboud university medical center, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
Michiel Coppens, MD, PhD

Medical Specialist
Department of Vascular Medicine, Amsterdam UMC location University of Amsterdam, 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
JJ

Joop Jansen

Professor of Experimental Hematology
Department of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, the Netherlands
Nijmegen, Gelderland, 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
Lv

Lize F.D. van Vulpen

Internist Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands
DM

Daniëlle Meijer

Clinical chemist
Department of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
SS

Saskia E.M. Schols

Internist-hematologist
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands. Hemophilia Treatment Center Nijmegen – Eindhoven – Maastricht, The Netherlands
Nijmegen, Gelderland, Netherlands

Background: Heterogeneity in clinical bleeding phenotype is observed in hemophilia patients with similar factor VIII or factor IX activity levels. Thrombin generation (TG) as a global hemostasis assay may contribute to better predict which patients are at increased risk of bleeding.

Aims: To quantify the association between clinical bleeding phenotype and TG profile in hemophilia patients.

Methods: The Nijmegen Hemostasis Assay (NHA), which simultaneously measures TG and plasmin generation, was performed in 863 hemophilia patients (adults and children) originating from the sixth Hemophilia in the Netherlands study. Patients using prophylaxis underwent a washout period. Ethical approval and written informed consent were obtained. Severe clinical bleeding phenotype was defined as an annual bleeding rate (ABR) ≥5 or an annual joint bleeding rate (AJBR) ≥3. Correlations were determined using Spearman’s correlation test.

Results: TG parameters significantly differed between hemophilia patients and healthy controls (thrombin peak height (TPH) in severe 1.0nM [IQR 1.0-1.0], moderate 25.5nM [1.0-46.5], mild hemophilia A 47.4nM [27.9-71.1], and controls 266.5nM [252.8-280.6]; thrombin potential in severe 1.0nM·min [1.0-1.0], moderate 607.6nM·min [1.0-1083.0], mild hemophilia A 1034.0nM·min [668.4-1398.0], and controls 2088.0nM·min [1988.0-2175.0]). Weak but significant correlations were found between clinical bleeding phenotype and TPH (ABR r=-0.2571; AJBR r=-0.2776) or thrombin potential (ABR r=-0.2752; AJBR r=-0.3084) (Figure 1). A severe clinical bleeding phenotype was observed in patients with a TPH < 35% and a thrombin potential < 70%, independent of hemophilia severity. Median TPH and thrombin potential were significantly lower in patients with a severe clinical bleeding phenotype versus a mild clinical bleeding phenotype (TPH: 0.4% vs 17%; thrombin potential 0.05% vs 46%) (Figure 2).

Conclusion(s): A decreased TG profile is associated with severe clinical bleeding phenotype in hemophilia patients. TG parameters in combination with clinical bleeding severity may be better tools to personalize prophylactic replacement therapy, irrespective of hemophilia severity.