Viral hepatitis in haemophilia: historical perspective and current management

The introduction of clotting factor concentrates has substantially improved the lives of people with clotting factor deficiencies. Unfortunately, the transmission of blood-borne viral infections through these plasma-derived products led to a huge epidemic of human immunodeficiency virus and viral hepatitis in people with haemophilia (PWH). In a significant proportion of PWH exposed to these viruses, the ensuing decades-long chronic infection resulted in excess morbidity and mortality. Fortunately, developments in the safety of blood products, as well as vaccination and highly effective antiviral treatments have improved the prospects of PWH. The present article reviews the background of the viral hepatitis epidemic in PWH, the natural history of hepatitis B and C infections and their long-term management

Prenatal diagnosis for haemophilia: A nationwide survey among female carriers in the Netherlands

Carriers of haemophilia face difficult choices regarding prenatal diagnosis, but little is known about the determinants that influence their decisions. The aim of this study was to assess the incidence of prenatal diagnosis and potential determinants affecting the choice for prenatal diagnosis. A nationwide survey was performed among all women who underwent carriership testing for haemophilia in the Netherlands between 1992 and 2004. Prenatal diagnosis was assessed i

Thirty years of hemophilia treatment in the Netherlands, 1972-2001

Since the introduction of replacement therapy in the early 1960s by the infusion of plasma-derived factor VIII and IX preparations, important changes have occurred for hemophilia patients. We studied the medical and social developments over 30 years of hemophilia treatment. Since 1972, 5 cross-sectional national postal surveys among all hemophilia patients in the Netherlands were performed, the latest in 2001. The prestructured questionnaires included items on treatment, the presence of inhibitory antibodies against factor VIII or IX, the annual number of bleeding episodes, use of inpatient hospital care, and hepatitis C and HIV infections. Response rate in 2001 was 70%. Young patients ( <16 years) with severe hemophilia showed the largest increase in use of prophylaxis, from 34% in 1972 to 86% in 2001. The occurrence of hemorrhages has gradually decreased. Hospital admissions decreased from 47% of all patients in 1972 to 18% in 2001. Our study shows that the treatment of patients with severe hemophilia in the Netherlands has focused on the use of prophylactic treatment, especially in children. This has resulted in a decrease in bleeding frequency and an improvement of the medical and social circumstances of patient

Effect of fibrinolysis on bleeding phenotype in moderate and severe von Willebrand disease

Item does not contain fulltextPatients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on bleeding tendency in VWD patients has not been investigated. We hypothesized that enhanced fibrinolysis may result in a more severe bleeding phenotype. Therefore, we measured the fibrinolytic potential in patients with moderate or severe VWD to investigate the contribution of fibrinolysis to the bleeding tendency. Fibrinolytic potential was measured as plasma clot lysis time (CLT) with and without addition of potato carboxypeptidase inhibitor (PCI) in 638 patients with moderate or severe VWD who participated in a nationwide multicentre cross-sectional study. Bleeding severity was measured using the Bleeding Score (BS).The CLTs were significantly longer, indicative of hypofibrinolysis, in men compared to women with VWD [106.2 (IQR 95.7-118.1) vs. 101.9 (IQR 92.8-114.0) min]. The CLTs prolonged with increasing age. No association was found between VWF or FVIII levels and CLT, or between VWF or FVIII levels and CLT(+PCI) . No association was observed for BS in a model with 10log-transformed CLT, adjusted for age, gender, VWF:Act and FVIII [b = 6.5 (95%CI -0.3 to 13.4)]. Our study showed that the plasma fibrinolytic potential does not influence bleeding tendency in VWD patients and therefore does not explain the variability in bleeding phenotype in VWD.1 mei 201

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

Thrombosis and Hemostasi

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. VWF antigen (VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0·23 iu/ml, 95% confidence interval (CI): 0·11–0·35], diabetes mellitus (0·11 iu/ml, 95% CI: −0·02 to 0·23), cancer (0·14 iu/ml, 95% CI: 0·03–0·25) and thyroid dysfunction (0·14 iu/ml, 95% CI: 0·03–0·26) than in patients without these comorbidities (all corrected for age, sex and blood group). Similar results were observed for VWF collagen binding capacity (VWF:CB), VWF activity as measured by the VWF monoclonal antibody assay (VWF:Ab) and factor VIII (FVIII) coagulant activity (FVIII:C). In type 1 VWD, age was associated with higher VWF:Ag (0·03 iu/ml; 95% CI: 0·01–0·04), VWF:CB (0·02 iu/ml; 95% CI: 0·00–0·04), VWF:Ab (0·04 iu/ml; 95% CI: 0·02–0·06) and FVIII:C (0·03 iu/ml; 95% CI: 0·01–0·06) per decade increase. After adjustment for relevant comorbidities, these associations were no longer significant. Despite the higher VWF and FVIII levels, type 1 VWD patients with comorbidities had more bleeding episodes, particularly during surgery. There was no association between comorbidities and VWF/FVIII levels or bleeding phenotype in type 2 VWD patients. In conclusion, comorbidities are associated with higher VWF and FVIII levels in type 1 VWD and may explain the age-related increase of VWF and FVIII levels

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. Methods: Patients were included from the “WiN study