Diagnostic and therapeutic flowchart for VWD. The finding of low VWF (A), the confirmation in a family member with established VWD (B), or the evaluation of bleeding symptoms of unknown origin (C) demands a diagnostic process for VWD only when both the bleeding score is significantly elevated and the VWF:Ag or VWF:RCo levels are less than 40 IU/dL (either confirmed or consistently reported in patient clinical records). For children and young subjects with few historical hemostatic challenges, the requirement for a high bleeding score is less stringent. VWD type 2N may only be apparent with a reduced FVIII:C level. Once VWD is confirmed, if not already available in a related family member, a desmopressin trial infusion should be performed in all cases in which RIPA is not enhanced. Type-specific diagnosis is not required for clinical practice. Desmopressin should be the first treatment of choice for either treatment or prophylaxis of any minor spontaneous, traumatic, or surgical bleeding or delivery. Home treatment is feasible for selected patients. Replacement therapy should be used for major bleeding or major surgery in desmopressin-responsive patients and for all nontrivial bleeding symptoms that fail local or ancillary interventions in desmopressin-unresponsive VWD patients (or those with enhanced RIPA). *Discrepantly reduced FVIII may suggest type 2N VWD.