Congenital von Willebrand disease type I: definition, phenotypes, clinical and laboratory assessment

Von Willebrand disease, with a prevalence of about 1% in the general population, is the most frequent inherited bleeding disorder. Among the major subtypes, type I von Willebrand disease represents by far the more prevalent category (about 70%) and includes cases with a partial deficiency of plasma von Willebrand factor and no evidence of qualitative defects. The clinical expression as well as the laboratory phenotype of the disorder and its penetrance are greatly variable. The diagnosis usually requires the presence of autosomally inherited bleeding history co-segregating with a low von Willebrand factor level. The influence of several genetic and acquired conditions on the level of von Willebrand factor is however, widely appreciated and represents the major obstacle in correctly identifying von Willebrand disease as the cause of a bleeding diathesis in several families. The molecular genetics of the minority of cases showing high penetrance and expressivity of the phenotype are unravelling, but for the large majority of milder cases, the molecular basis is still unknown. We present a practical approach to diagnosis, based on scientific evidence and direct experience. The implications of the diagnosis of von Willebrand disease for the patient's quality of life are also considered.