Diagnosis of von Willebrand disease subtypes: implications for treatment

Abstract

von Willebrand disease (VWD) is a complex congenital bleeding disorder that is characterized by different quantitative and/or qualitative defects in von Willebrand factor (VWF). The diagnosis of VWD remains a challenge to the treating physician because of clinical and laboratory variability; many patients are oligosymptomatic and no single laboratory test is entirely diagnostic. Thus, a combination of patient medical history as well as several laboratory tests must be utilized to accurately diagnose and characterize the disease. The introduction of molecular techniques in the last two decades has greatly improved the ability to characterize the genetic variants of the disease. In contrast, however, progress in improving methods to classify the disease phenotype has been much slower. The current 'gold standard' for classifying VWD is the evaluation of VWF multimers, which enables the different types and subtypes of the disease to be discriminated. However, this method is technically demanding, not easy to standardize, and has not improved considerably over the last 25 years. This article reviews the current methods used to diagnose and characterize VWD and issues in the treatment of this complex disease.