Patients with moderate hemophilia A and B with a severe bleeding phenotype have an increased burden of disease

Marieke J A Verhagen; Erna C van Balen; Nicole M A Blijlevens; Michiel Coppens; Waander L van Heerde; Frank W G Leebeek; Sanna R Rijpma; Lize F D van Vulpen; Samantha C Gouw; Saskia E M Schols

doi:10.1016/j.jtha.2023.09.029

Patients with moderate hemophilia A and B with a severe bleeding phenotype have an increased burden of disease

J Thromb Haemost. 2024 Jan;22(1):152-162. doi: 10.1016/j.jtha.2023.09.029. Epub 2023 Oct 7.

Affiliations

¹ Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, the Netherlands; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
² Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
³ Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Department of Vascular Medicine and Haemophilia Treatment Center, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, the Netherlands; Enzyre BV, Novio Tech Campus, Nijmegen, the Netherlands.
⁶ Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
⁷ Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁸ Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁹ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Amsterdam UMC Location University of Amsterdam, Department of Pediatric Hematology, Meibergdreef 9, Amsterdam, the Netherlands.
¹⁰ Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, the Netherlands. Electronic address: [email protected].

PMID: 37813197
DOI: 10.1016/j.jtha.2023.09.029

Abstract

Background: Patients with moderate hemophilia express varying bleeding phenotypes.

Objectives: To assess the burden of disease in patients with moderate hemophilia and a mild or severe phenotype incorporating the thrombin generation profile.

Methods: This sub-study of the 6th Hemophilia in the Netherlands study, analyzed data of adults with moderate hemophilia A or B. Patient characteristics and information on bleeding tendency, joint status, and quality of life were obtained from electronic patient files and self-reported questionnaires. A severe bleeding phenotype was defined as an annual bleeding rate ≥5, an annual joint bleeding rate ≥3, and/or the use of secondary/tertiary prophylaxis, and a mild phenotype vice versa. TG was measured with the Nijmegen Hemostasis Assay.

Results: This study included 116 patients: 21% had a severe phenotype of whom 46% used prophylaxis. Patients with a severe phenotype treated on demand reported a higher median annual bleeding rate (7), annual joint bleeding rate (3), and more frequently an impaired joint (77%) than patients with a severe phenotype on prophylaxis (2; 0; 70%) or patients with a mild phenotype (0; 0; 47%). Furthermore, patients with a severe phenotype treated on demand experienced a more decreased quality of life. Despite similar factor activity levels, patients with a severe phenotype had a lower thrombin peak height and thrombin potential (0.7%; 0.06%) than patients with a mild phenotype (21.3%; 46.8%).

Conclusion: Patients with moderate hemophilia and a severe phenotype treated on demand displayed a high burden of disease as well as a low thrombin generation profile advocating them toward more intensive prophylactic treatment.

Keywords: hemophilia A; hemophilia B; phenotype; quality of life; thrombin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cost of Illness
Factor VIII / therapeutic use
Hemarthrosis / prevention & control
Hemophilia A* / complications
Hemophilia A* / diagnosis
Hemophilia A* / epidemiology
Hemorrhage / drug therapy
Humans
Phenotype
Quality of Life
Thrombin / therapeutic use

Substances

Thrombin
Factor VIII