Pathophysiology of AVWS. (A) Increased clearance of VWF or inhibition of VWF activity as seen in disorders such as systemic lupus erythematosis or myeloproliferative disorders resulting in decreased circulating VWF antigen and decreased VWF activity. (B) Adsorption of VWF (particularly high-molecular-weight [HMW] multimers) to tumor cells as is seen in Wilms tumor or other malignancies resulting in decreased circulating VWF. (C) Increased shear stress resulting in access of VWF cleavage sites and clearance of HMW multimers resulting in decreased levels of circulating VWF and decreased HMW multimers. (D) Decreased production of VWF as is seen hypothyroidism and possibly valproic acid treatment. LMW, low molecular weight.