Von Willebrand disease protects against arterial thrombosis

Background and Aims: Von Willebrand disease (VWD) is caused by reduced levels of or dysfunctional von Willebrand factor (VWF) and is characterized by a bleeding tendency. It is well known that individuals with high VWF levels have a higher risk for arterial thrombosis. Although it has never been studied, we hypothesized that VWD patients may be protected against arterial thrombotic events. Therefore, we investigated the occurrence and prevalence of arterial thrombosis in a large cohort of VWD patients in comparison to the general population. Materials and Methods: We studied clinical history of arterial thrombosis in 637 adult VWD patients (aged 16-85 years, 36.6% men) in a large nation-wide multicenter cross-sectional study with VWF levels ≤ 0.30 IU/mL (Willebrand in the Netherlands - WiN study). Clinical history of cardiovascular and cerebrovascular events and cardiovascular risk factors were obtained by a questionnaire. Subsequently, medical records were reviewed for all subjects who reported an event to objectify the arterial thrombosis. The prevalence was compared with data of the Dutch general population. Results: Twenty-one of the 637 (3.3%) adult VWD patients had a history of arterial thrombosis. Five patients (0.8% (95%CI 0.1-1.5) suffered from acute myocardial infarction and 3 patients (0.5% (95%CI 0-1.0)) had an ischemic stroke. Furthermore, unstable angina pectoris was recorded in 8 patients and transient ischemic attacks in 6. Eight patients had more than one event. In comparison with the Dutch general population, VWD patients ≥ 45 years had a significantly lower than expected prevalence and standardized morbidity ratio of coronary heart disease, acute myocardial infarction and ischemic stroke (see Table). No statistical significant difference in VWF and FVIII levels was observed between VWD patients with and without arterial thrombosis. Conclusions: Our study shows for the first time that VWD patients are protected against coronary heart disease, acute myocardial infarction and ischemic stroke. (Table Presented).