Reduced cardiovascular morbidity in patients with hemophilia: results of a 5-year multinational prospective study.

Hemophilia is a congenital bleeding disorder caused by low levels of clotting factor VIII or IX. The life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased; in retrospective studies, there are conflicting data regarding if, despite this increase, the incidence is still lower than in the general population.

Hepatitis C virus in hemophilia: Health-related quality of life after successful treatment in the sixth Hemophilia in the Netherlands study.

Introduction: Persons with hemophilia and hepatitis C virus (HCV) infection have a lower health-related quality of life (HRQoL) than those never HCV infected. However, it is unknown whether HRQoL after HCV eradication is comparable to individuals never HCV infected. We aimed to compare HRQoL between HCV-cured and never chronically HCV-infected persons with hemophilia.

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

Introduction: Despite increasing awareness of issues faced by women and girls with inherited BDs (WGBD), standards of care are lacking, with disparities in diagnosis and treatment for WGBD across Europe. We aimed to develop practical principles of care (PoC) to promote standardization of care for WGBD within European Haemophilia Treatment and Comprehensive Care Centres (HTC/CCCs).

Methods: The co-creation process, supported by the European Association for Haemophilia and Allied Disorders, consisted of four multidisciplinary meetings with health care providers (HCPs) experienced in WGBD care, and European Haemophilia Consortium representatives, combined with broad patient and HCP consultations in the European haemophilia community.

Clinical management of woman with bleeding disorders: A survey among European haemophilia treatment centres.

Introduction: The impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist.

Aim: To examine practices and define research priorities on diagnosis and management of WBD in Europe.

Catheter Ablation for Atrial Fibrillation in Patients with Hemophilia or von Willebrand Disease.

 Management of atrial fibrillation (AF) is complex in patients with bleeding disorders. Catheter ablation such as pulmonary vein isolation (PVI) has been suggested in cases with bleeding disorders. However, data on safety are missing.

Sports participation and physical activity in patients with von Willebrand disease.

Introduction: Patients with bleeding disorders may experience limitations in sports participation and physical activity. Several studies on sports participation have been performed in haemophilia patients, but studies in patients with von Willebrand disease (VWD) are lacking.

Aim: We assessed the sports participation and physical activity of a large cohort of VWD patients.

Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to Haemophilia A: A Post Hoc Analysis.

Long-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1-5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0-124), X-ray Pettersson scores (PS, 0-13/joint) and the Haemophilia Activities List (HAL, 0-100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD,  = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds.

The Impact of Hepatitis C Virus Direct-Acting Antivirals on Patient-Reported Outcomes: A Dutch Prospective Cohort Study.

Introduction: Pegylated interferon-based therapy for hepatitis C virus (HCV) negatively impacts nutritional state and patient-reported outcomes (PROs) such as health-related quality of life (HRQL). Clinical trials with direct-acting antivirals (DAAs) report significant PRO improvement but real-world data are still scarce.

Methods: Prospective cohort study recruiting HCV patients treated with DAAs in 2015-2016.

Comorbidities associated with higher von Willebrand factor (VWF) levels may explain the age-related increase of VWF in von Willebrand disease.

Some comorbidities, such as hypertension, are associated with higher von Willebrand factor (VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease (VWD). Therefore, we studied this association in patients with type 1 (n = 333) and type 2 (n = 203) VWD from the 'WiN" study.

Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study.

Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life.

Joint assessment in von Willebrand disease. Validation of the Haemophilia Joint Health score and Haemophilia Activities List.

Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and reliability of the Haemophilia Joint Health Score (HJHS) and Haemophilia Activities List (HAL) in patients with Von Willebrand disease (VWD).

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network.

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening.

von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease.

Unlabelled: The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (

Fviii: C) and VWF antigen (VWF:Ag) reflect synthesis, secretion, and clearance of VWF. We aimed to define the pathophysiology of 658 patients with type 1, 2, or 3 von Willebrand disease (VWD) with VWF levels ≤30 U/dL from the Willebrand in The Netherlands (WiN) study using the VWFpp/VWF:Ag and

Fviii: C/VWF:Ag ratios. We evaluated the use of VWFpp in the classification and diagnosis of VWD.

Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial.

This multinational, randomized, single-blind trial investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously treated patients with hemophilia B (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to either 10 IU/kg or 40 IU/kg once weekly or to on-demand treatment of 28 weeks. No patients developed inhibitors, and no safety concerns were identified.

Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders.

Background & Aims: Patients with inherited bleeding disorders are an interesting group to study the long-term course of chronic hepatitis C virus (HCV) infection, because of their uniform mode of infection and reliable follow-up. Our aim was to assess the long-term occurrence of adverse liver-related events in these patients.

Methods: The occurrence and determinants of end-stage liver disease (ESLD) were assessed using retrospective data of 863 HCV infected patients with inherited bleeding disorders from the Netherlands and the UK.

Unfavourable cardiovascular disease risk profiles in a cohort of Dutch and British haemophilia patients.

Cardiovascular disease (CVD) mortality is reported to be decreased in haemophilia patients, but reports on the prevalence of CVD risk factors are conflicting. A cross-sectional assessment of CVD risk profiles was performed in a large cohort of haemophilia patients. Baseline data on CVD risk factors of 709 Dutch and UK haemophilia patients aged ≥30 years were analysed and compared with the general age-matched male population.

Increased prevalence of hypertension in haemophilia patients.

An increased prevalence of hypertension is reported in haemophilia patients, but data from large, unbiased studies are lacking. The aim of our study was to cross-sectionally assess the prevalence of hypertension in a large cohort of 701 haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and 315 UK haemophilia patients aged 30 years or older were analysed and compared with the general age-matched male population.

Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease.

We performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels ≤30 U/dl. Menorrhagia (85%), cutaneous bleeding (77%), bleeding from minor wounds (77%) and oral-cavity bleeding (62%) occurred most frequently.

History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia.

Objective: Cardiovascular disease (CVD) mortality is reported to be lower in haemophilia patients than in the general population, but information on the occurrence of non-fatal CVD is lacking. The aim of our study was to assess CVD history in a cohort of living haemophilia patients.

Methods: Retrospective data on the occurrence of myocardial infarction, angina pectoris, ischaemic stroke and intracranial bleeding in 709 living Dutch and British haemophilia patients aged 30 yr or older were analysed and compared with the general age-matched male population.

Non-fatal cardiovascular disease, malignancies, and other co-morbidity in adult haemophilia patients.

Introduction: With increasing life expectancy, more haemophilia patients will be confronted with age-related problems. To ensure optimal care, it is important to know the occurrence of both fatal and non-fatal cardiovascular disease, malignancies and other types of co-morbidity in these patients. Our aim was to retrospectively assess the occurrence of co-morbidity and causes of death in a substantial birth-cohort of haemophilia patients.

Coronary artery calcification in hemophilia A: no evidence for a protective effect of factor VIII deficiency on atherosclerosis.

Objective: Ischemic heart disease mortality is lower in hemophilia patients than in the general male population. As coagulation plays a role in the inflammatory pathways involved in atherogenesis, we investigated whether the clotting factor deficiency protects hemophilia patients from developing atherosclerosis.

Methods And Results: Coronary artery calcification, measured with multidetector-row computed tomography, was compared between 42 men, ≥59 years, with severe or moderate hemophilia A, and 613 nonhemophilic men from the Rotterdam Study, a prospective population-based study.