The physiological relevance of this pH-dependent spring-loaded VWF packing and the subsequent rapid release of long VWF multimers is evident, for example, in von-Willebrand disease, the most common inherited bleeding disorder, in which VWF levels, packing and/or secretion are compromised due to mutations, in most cases in the VWF gene itself (for reviews see [18, 19]). This evidence concerns the gene VWF and Von Willebrand disease.