The role of molecular genetics in diagnosing von Willebrand disease

von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans, but its diagnosis, using conventional clinical criteria and phenotypic hemostasis test results, can be problematic. The von Willebrand factor gene was cloned in the mid-1980s, and since that time, a significant amount of information has been gathered with respect to the molecular pathology responsible for this trait. This accumulated information, along with advances in genetic technology, has now made the integration of molecular genetic testing for VWD a feasible option in some instances. In this review, we have summarized the current state of knowledge concerning the genetic causation of the various forms of VWD. We have also provided guidelines as to how genetic testing can be used to clarify diagnostic uncertainty that might remain after a clinical evaluation and routine coagulation testing has been completed.