Von Willebrand disease: 80 year-old without wrinklesl

In 1926 Erik von Willebrand decribed a novel bleeding disorder in a large family from Foglo on the islands of Aland in the Gulf of Bothnia. At variance with the well known X-linked inheritance of Hemophilia, the epitome of inherited bleeding disorders, both sexes were equally affected, suggesting an autosomal pattern of inheritance, Mucosal bleeding was the dominant symptom, while hemarthrosis and muscle hematoma were rare. The latter finding, together with the observation of a prolonged bleeding time with normal platelet count, led von Willebrand to surmise a functional disorder of the platelets, associated with systemic lesion of the vessel wall, as the possible cause of the disorder. Only in the 50s, was it demonstrated that in these patients the prolonged bleeding time was associated with reduced FVIII, but we had to wait until the 70s to clarify that the deficiency of a new factor, called von Willebrand factor (VWF) and different from FVIII, was responsible for von Willebrand disease (VWD). Surprisingly, the reduction of this factor caused low FVIII, pointing to the strict relationships between the two factors. The cloning in the 80s of VWF gene has settled the basis to unravel the molecular causes of the disorder. In his paper, Federici summarizes the milestones in the history of von Willebrand disease. Despite the fact that the history of the disorder dates back to 1926,1 several questions about molecular genetics, diagnostic criteria, laboratory methodology and clinical history remained and only recently important insights have been provided by relevant publications about these issues.