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Summary. Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related differences in bleeding phenotype between elderly VWD patients and those < 65 years. We also studied co-morbidity in elderly patients. Patients/ Methods: We included VWD patients with VWF levels ≤ 30 U dL À1 in the nationwide cross-sectional 'Willebrand in the Netherlands' (WiN-) study. Patients reported bleeding episodes and treatment of VWD in the year preceding inclusion and during life. This was compared between VWD patients older (n = 71) and younger (16-64 years, n = 593) than 65 years. In elderly patients, agerelated changes in VWF and FVIII levels were studied longitudinally by including all historically measured levels. All medical records were examined for co-morbidity. Results: In elderly type 1 patients, a decade age increase was associated with a 3.5 U dL À1 (95% CI, À0.6 to 7.6) VWF:Ag increase and 7.1 U dL À1 (95% CI, 0.7 to 13.4) FVIII:C increase. This increase was not observed in elderly type 2 patients. Elderly type 2 patients reported significantly more bleeding symptoms in the year preceding inclusion than younger patients (16/27, 59% vs. 87/ 221, 39%; P = 0.048), which was not observed in type 1 VWD. Conclusions: von Willebrand factor parameters and bleeding phenotype evolve with increasing age in VWD. VWF and FVIII levels increase with age in type 1 patients with no mitigation in bleeding phenotype. In type 2 patients VWF parameters do not increase with age and in these patients aging is accompanied by increased bleeding.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Background Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands. Objective This observational cohort study aimed to assess all‐cause and cause‐specific mortality in patients with hemophilia in the Netherlands between 2001 and 2018 and to compare mortality and life expectancy with previous survival assessments from 1973 onward. Patients/methods All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018. Results Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow‐up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2–1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, 6 years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased, and death due to ischemic heart disease has remained consistently low over time. Conclusions Survival in patients with hemophilia in the Netherlands has improved over time but is still lower than that of the general population.

Ageing haemophilia patients are increasingly confronted with ischaemic heart disease (IHD). Treatment is complex because of the delicate equilibrium between bleeding and thrombosis. In 2009, we developed an institutional guideline on how to treat IHD in this patient population. The aim of this study was to evaluate feasibility and safety of this guideline. Haemophilia patients who underwent coronary angiography or percutaneous coronary intervention between January 2009 and June 2012 were included in the current case series. Nine diagnostic or therapeutic cardiac catheterizations were performed in six haemophilia patients. One patient with moderate haemophilia B was included, whereas the other patients had mild haemophilia A. In six of nine procedures, access to the circulation was gained via the radial artery. Only bare-metal stents were implanted, after which dual antiplatelet treatment was given for at least 4 weeks. During cardiac catheterization/intervention and dual antiplatelet treatment, clotting factor levels were corrected. No thrombotic or clinically relevant bleeding complications occurred. In one patient, a low-titre inhibitor recurred 10 months after catheterization. In-stent restenosis was diagnosed in one patient. This case series indicates that treatment according to the guideline is feasible and safe. Furthermore, based on the case series and developments in new guidelines for non-haemophilic patients with IHD, some adjustments on the 2009 guideline are proposed.