Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders.

Background: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)).
Methods: We included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder.
Findings: We included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, p  = 0.002). Age of first bleeding was similar between men and women, respectively 8.9 ± 13.6 (mean ±sd) years and 10.6 ± 11.3 years ( p  = 0.075). However, the diagnostic delay, which was defined as time from first bleeding to diagnosis, was longer in women (11.6 ± 16.4 years) than men (7.7 ± 16.6 years, p  = 0.002). Similar results were found when patients referred for bleeding were analyzed separately. Of women aging 12 years or older, 469 (77.1%) had received treatment because of sex-specific bleeding.
Interpretation: Women with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding.
Funding: The WiN study was supported (in part) by research funding from the Dutch Hemophilia Foundation (Stichting Haemophilia), Shire (Takeda), and CSL Behring (unrestricted grant).
Competing Interests: F. Atiq received the CSL Behring-professor Heimburger Award 2018 and a travel grant from Sobi. J.L. Saes and S.E.M. Schols received travel support from Bayer, Takeda and Sobi. F.W.G. Leebeek received research support from CSL Behring and Shire/Takeda for performing the Willebrand in the Netherlands (WiN) study, and from UniQure and Sobi for other studies. He is consultant for UniQure, Novo Nordisk, BioMarin and Shire/Takeda, of which the fees go to the institution, and has received a travel grant from Sobi. He is also a DSMB member for a study by Roche. H.C.J. Eikenboom received research support from CSL Behring and he has been a teacher on educational activities of Roche. K.P.M. van Galen received unrestricted research support from CSL Behring and Bayer and speakers fee from Takeda, CSL Behring and Bayer. J.G. van der Bom has been a teacher on educational activities of Bayer. M.H. Cnossen has received grants from governmental research institutes, such as the Dutch Research institute (NOW), ZonMW, Innovation fund, NWO-NWA and unrestricted investigator initiated research grants as well as educational and travel funding from various companies over the years (Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, novo Nordisk, Novartis and Nordic Pharma), and has served as a member on steering boards of Roche and Bayer. All grants, awards and fees go to the Erasmus MC as an institution. The institution of K. Fijnvandraat has received unrestricted research grants from CSL Behring, Sobi and NovoNordisk and her institution received consultancy fees from Grifols, Takeda, Novo Nordisk and Roche. K. Meijer received research support from Bayer, Sanquin and Pfizer; speaker fees from Bayer, Sanquin, Boehringer Ingelheim, BMS and Aspen; consulting fees from Uniqure, of which all fees go to the institution. B.A.P. Laros‐van Gorkom has received unrestricted educational grants from Baxter and CSL Behring. M.J.H.A. Kruip received grants from governmental research institutes, such as the Dutch Research institute (ZonMW/NWO), Dutch Thrombosis Foundation, Innovation fund, unrestricted grants from Bayer, Pfizer, Daiichi Sankyo, Sobi and Boehringer Ingelheim and speakers fee from Bayer. R.E.G. Schutgens received grants from Bayer, grants from Baxalta, Pfizer, NovoNordisk. The institution of M. Peters received an unrestricted research grant from Pfizer. F.J.M. van der Meer received grants from CSL Behring, Pfizer, Bayer, Novo Nordisk, Sobi, Roche, and OctaPharma. W.L. van Heerde reports speaker and consultant and travel fees from Takeda, Bayer, CSL Behring, and Sobi. He is also founder and co-owner of Enzyre. None of the other authors has a conflict of interest to declare.
(© 2021 The Authors.)