Von Willebrand disease: classification and epidemiology

Abstract

Von Willebrand disease (VWD) is a highly heterogeneous inherited bleeding disorder caused by reduced levels or activity of von Willebrand factor (VWF). VWD is associated with a wide spectrum of clinical and laboratory phenotypes, but diagnosis is based on three main criteria: a positive bleeding history, low levels of circulating VWF and autosomal inheritance patterns. VWD is classified into quantitative VWF deficiencies (type 1, partial and type 3, almost total) and peculiar qualitative defects (type 2 A, B, M, and N). The prevalence of VWD has been estimated by epidemiological investigations to be ~1%, but a clear-cut diagnosis in clinical practice is often not possible because of several confounding factors influencing plasma VWF levels, especially in mild cases. The prevalence of clinically relevant VWD could range from 1/1,000-10,000 inhabitants based on patients referred to tertiary care centers. Recent genetic prevalence data however suggest that pathogenic VWF variants or putative disease alleles may be significantly more common than 1%.