For most patients, bleeding is mild under most circumstances. However, if trauma occurs or surgery is scheduled, cryoprecipitate or desmopressin acetate (DDAVP) or Stimate can be given to raise the levels of Von Willebrand factor, which will decrease the tendency toward bleeding. Fresh plasma or certain factor VIII preparations may also be used to decrease bleeding.

Some subtypes of Von Willebrand's disease do not respond to DDAVP. Because of this, the subtype should be determined prior to reliance on DDAVP for a significant bleeding challenge. In addition, a trial of DDAVP can be done prior to surgery to test whether Von Willebrand factor levels increase. Patients with this disorder should not take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen without consulting their health care provider.