International guidelines conditionally recommend long-term prophylaxis in patients with von Willebrand disease (VWD) and severe/frequent bleeding. As recombinant von Willebrand factor (rVWF, vonicog alfa) may reduce the frequency of treated spontaneous bleeding events (BEs), we investigated the efficacy and safety of rVWF prophylaxis in adults with severe VWD. Patients with BEs requiring VWF therapy in the past year (on-demand VWF therapy [Prior On-Demand group] or plasma-derived VWF prophylaxis [pdVWF; Switch group]) were enrolled in a prospective, open-label, nonrandomized, phase 3 study. Planned duration of rVWF prophylaxis was 12 months; starting rVWF dose was 50±10 VWF:RCo IU/kg twice weekly (Prior On-Demand group) or based on prior pdVWF weekly dose/dosing frequency (Switch group). The primary endpoint was annualized bleeding rate of treated spontaneous BEs (sABR) during rVWF prophylaxis. Over the 12-month study period, treated sABR decreased by 91.5% on-study versus historical sABR in 13 patients in Prior On-Demand group, and by 45.0% in 10 patients in Switch group (model-based analysis ratio [95% CI]: 0.085 [0.021-0.346] and 0.550 [0.086-3.523], respectively). No treated spontaneous BEs were recorded in 84.6% (11/13) and 70.0% (7/10) of patients, respectively. The safety profile of rVWF was consistent with the previously established profile, with no new adverse drug reactions identified. Findings suggest that rVWF prophylaxis can reduce treated spontaneous BEs in patients previously receiving on-demand VWF therapy and maintains at least the same level of hemostatic control in patients who switch from prophylaxis with pdVWF to rVWF, with a favorable safety profile. Trial registration: www.clinicaltrials.gov (#NCT02973087) and www.clinicaltrialsregister.eu (#EudraCT 2016-001478-14).

Objective: To understand the impact of von Willebrand disease (VWD) on women's health, a retrospective cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) GOLD database and Hospital Episode Statistics (HES) Admitted Patient Care data from 1988 to 2016. Materials and Methods: Hysterectomy and heavy menstrual bleeding (HMB) events were identified by recorded disease/clinical codes and compared in women with and without VWD (matched 1:10 by birth and CPRD record start years [±2 years], and general practice attended). Incidence rates and incidence rate ratios (IRR) were calculated; risks were estimated using the Kaplan–Meier method. Results: HMB was recorded after cohort entry in 388 of 1,335 women (29.1%) with VWD and 1,524 of 12,463 women (12.2%) without VWD. The cumulative incidence of HMB was higher in women with versus without VWD across all ages ( p < 0.0001), and irrespective of prior HMB status ( p < 0.001). Women with VWD were more likely to have HMB compared with women without VWD; IRR adjusted for age and prior HMB status was 2.74 (95% confidence interval [CI]: 2.44–3.07). Hysterectomy was recorded in 88 of 1,374 women (6.4%) with VWD and 320 of 12,791 women (2.5%) without VWD. The cumulative incidence of hysterectomy was higher for women with versus without VWD ( p < 0.0001), and highest among women aged ≥30 years at cohort entry. Women with VWD aged 30 − 39 years were more likely to undergo hysterectomy than women without VWD; IRR adjusted for prior HMB was 3.58 (95% CI: 2.36 − 5.44). Conclusions: These findings highlight the substantial impact of VWD on women's health.

Objectives: To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD).Methods: This post hoc analysis of a phase 3 open-label trial provides a more detailed analysis of adults with type 3 VWD, categorized based on prior treatment at screening: "Prior On-Demand (OD)" (OD VWF; ≥3 documented spontaneous bleeding events [BEs] requiring VWF in previous 12 months) or "Switch" (plasma-derived[pd] VWF prophylaxis for ≥12 months). Annualized bleeding rates (ABRs) were evaluated during 12 months of rVWF prophylaxis versus historical data from medical records.Results: In the Prior OD group (n = 10), mean spontaneous ABR (sABR) for treated BEs was reduced by 91.6% (ratio, 0.08; 95% CI, 0.02-0.45) versus mean historical sABR. In the Switch group (n = 8), mean sABR for treated BEs was reduced by 47% (ratio, 0.53; 95% CI, 0.08-3.62). One non-serious adverse event (AE) was considered

Introduction Although hereditary von Willebrand disease (VWD) is the most common bleeding disorder, its epidemiology is not well understood. A systematic review (PROSPERO CRD42020197674/CRD42021244374) on the epidemiology/burden of illness of VWD was conducted to better understand patients’ unmet needs. Methods Observational studies (published January 1, 2010 to April 14, 2021) were identified in MEDLINE and Embase databases, using free-text keywords and thesaurus terms for VWD and outcomes of interest. Pragmatic web-based searches of the gray literature, including conference abstracts, were performed, and reference lists of retained publications were manually searched for additional sources. Case reports and clinical trials (phase 1–3) were excluded. Outcomes of interest were incidence, prevalence, mortality, patient characteristics, burden of illness, and therapeutic management/treatments currently used for VWD. Results Of the 3095 identified sources, 168 were included in this systematic review. Reported VWD prevalence (22 sources) ranged from 108.9 to 2200 per 100,000 in population-based studies and from 0.3 to 16.5 per 100,000 in referral-based studies. Reported times between first symptom onset and diagnosis (two sources; mean 669 days; median 3 years) highlighted gaps in timely VWD diagnosis. Bleeding events reported in 72–94% of the patients with VWD (all types; 27 sources) were mostly mucocutaneous including epistaxis, menorrhagia, and oral/gum bleeding. Poorer health-related quality of life (three sources) and greater health care resource utilization (three sources) were reported for patients with VWD than in general populations. Conclusion Available data suggest that patients with VWD experience high disease burden in terms of bleeding, poor quality of life, and health care resource utilization.

Background People diagnosed with von Willebrand disease (VWD) have reduced quality of life versus the general population, and there is limited evidence of increased rates of anxiety and/or depression among people diagnosed with VWD. Aim To understand the association between VWD and mental health outcomes. Design and Setting A retrospective cohort study was conducted using the UK Clinical Practice Research Datalink (CPRD) GOLD database (1988–2016). Methods People diagnosed with VWD were matched 1:10 to randomly selected people in the database without VWD based on sex, birth year ±2 years, CPRD record start year ±2 years, and general practice attended. Individuals were followed from VWD diagnosis or match date to censoring (first event date, CPRD end date, or death). Treated anxiety and treated depression were identified by a diagnostic Read Code and a prescription for anxiety/depression medication recorded within 90 days of each other, after VWD diagnosis/match date. Results Treated anxiety was recorded in 89 of 1119 (8.0%) people diagnosed with VWD and 624 of 10,423 (6.0%) without VWD (age- and sex-adjusted incidence rate ratio [IRR], 1.37; 95% confidence interval [CI], 1.10–1.71). Treated depression was recorded in 119 of 1083 (11.0%) people diagnosed with VWD and 846 of 9845 (8.6%) without VWD (adjusted IRR, 1.35; 95% CI, 1.11–1.63). Females aged 20–39 and 0–19 years were at greatest risk for treated anxiety and treated depression, respectively. Conclusion Higher rates of treated anxiety and depression were observed among people diagnosed with versus without VWD, predominantly in young females.