Von Willebrand disease type 1: A diagnosis in search of a disease

Abstract

Von Willebrand disease (VWD) type 1 is reported to be common but frequently is difficult to diagnose. Many people have nonspecific mild bleeding symptoms, von Willebrand factor (VWF) levels display low heritability, and low VWF levels (15% to 50% of normal) are weak risk factors for bleeding. Therefore, bleeding and low VWF levels often associate by chance. Even with stringent diagnostic criteria based on a triad of bleeding symptoms, a low VWF level, and a positive family history, the prevalence of "false-positive" VWD type 1 is comparable to the published prevalence of the disease. Consequently, many patients diagnosed with VWD type 1 do not have a specific hemorrhagic disease at all, which limits the utility of the diagnosis. This unfortunate reality is a consequence of trying to force patients into binary categories of "diseased" or "healthy" that are incompatible with the continuous biologic context in which VWF functions. The problem may be avoided by substituting an empirical epidemiologic approach like that applied to other modest risk factors for disease such as elevated cholesterol and high blood pressure. Such a risk management strategy could be generalized to include other hemorrhagic and thrombotic risk factors. © 2003 by The American Society of Hematology.