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

Abstract

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).

European principles of care for women and girls with inherited bleeding disorders

“…Significant diagnostic delays, which occur in most BDs, hamper accurate management especially for WGBD 3,6,23 . HMB can be the sentinel symptom of a BD, particularly in adolescents 24 .…”

“…Approximately one in five women who presents to a gynaecologist with heavy menstrual bleeding (HMB) have an underlying BD 1,2 . Yet, BD under‐diagnosis remains very common with median diagnostic delays of 8–16 years in women and girls 3–6 . Identification of haemophilia carriers (HCs) is inadequate, with genetic testing often delayed (median age 30 years), and 31% of women being unaware of their carrier status at time of delivery, despite a known family history 7,8 .…”

von Willebrand disease: what does the future hold?

“…7 Although this could partially be explained by a first bleeding episode at different ages, it has also been shown that the diagnostic delay following the first bleeding episode is longer in women than men. 8 Delayed diagnosis may result in missed treatment opportunities and increased morbidity (both medical and psychological). It is thus important to increase knowledge and awareness of VWD among (general) clinicians and public.…”

Knowledge gaps in bleeding disorders: Results from an objective structured oral examination in internal medicine residency training

“…People with bleeding disorders (PBD) commonly experience delays in diagnosis despite presenting with ‘(ab)normal’ bleeding symptomatology 1‐4 . These delays lead to poorer health outcomes, impair quality of life and may increase the risk of life‐threatening or fatal bleeding 1‐3,5 .…”