The bleeding phenotype in people with nonsevere hemophilia

Fabienne R. Kloosterman, Anne Fleur Zwagemaker, the DYNAMO study group, Catherine N. Bagot, Erik A.M. Beckers, Giancarlo Castaman, Marjon H. Cnossen, Peter Collins, Charles Hay, Michel Hof, Britta Laros Van Gorkom, Frank W.G. Leebeek, Christoph Male, Karina Meijer, Ingrid Pabinger, Susan Shapiro, Michiel Coppens, Karin Fijnvandraat, Samantha C. Gouw

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Abstract

Detailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P < .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.

Original languageEnglish
Pages (from-to)4256-4265
Number of pages10
JournalBlood advances
Volume6
Issue number14
DOIs
Publication statusPublished - 21 Jul 2022

Bibliographical note

Acknowledgments
The authors thank all the participants of the DYNAMO study and
thank the participating HTC research nurses. They especially
thank Bianca Bakker and Caroline van der Tol-Klopper for their
work on the execution of the central measurements of the baseline FVIII/IX activity levels.
This work was funded by a grant from Novo Nordisk and
supported by the Parelsnoer clinical biobank Hemophilia at the
Health-RI (funded by the Ministry of Health, Welfare and Sport).
The funding sponsor had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the
data; or preparation, review, and approval of the manuscript

Publisher Copyright:
© 2022 by The American Society of Hematology.

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