Everyone experiences minor
bleeding and clotting, and many illnesses feature extremes of
hemorrhage or
thrombosis. Recent advances have illuminated the ways in which
von Willebrand factor (VWF) contributes to both kinds of
hemostatic emergency, whether mundane or life threatening, often through disturbances in VWF synthesis or catabolism.
von Willebrand factor multimer assembly depends on the ability of the propeptide to promote
disulfide bond formation in the Golgi, possibly by acting as a pH-sensitive
oxidoreductase. Once secreted into the blood, multimers are subject to competing processes of clearance and of proteolysis by ADAMTS-13. Defects in the secretion or intravascular clearance of VWF can cause exceptionally severe forms of
von Willebrand disease (VWD) type 1. Defects in the assembly of VWF multimers, or exaggerated proteolytic degradation by ADAMTS-13, can cause VWD type 2A and contribute to VWD type 2B. Conversely, defects in the feedback proteolysis of VWF by ADAMTS-13 can cause
thrombotic thrombocytopenic purpura (
TTP). The pathophysiologic importance of VWF is not limited to the dramatic phenotypes of VWD and
TTP. In fact, VWF level also correlates with
thrombosis risk and inversely with
bleeding risk within the apparently healthy population. More research is needed to understand how VWF function is regulated, and to enable physicians to use this knowledge for the benefit of their patients.