Type 3 Von Willebrand disease (type 3 VWD) is the most severe and rare form of VWD.  It is characterized by a bleeding disorder associated with a total lack of Von Willebrand factor (VWF) in the plasma as well as in cellular compartments.  This type causes a profound deficiency of factor VIII (FVIII) level in plasma.  Annual incidence varies between countries.  However, it revolves around 1/500,000 in countries favoring consanguineous marriages.  Usually, the age of onset occurs in the neonatal period or in infancy.  The bleeding anomalies are characterized by mucocutaneous hemorrhage and prolonged bleeding after surgical interventions.  Affected individuals may have hematomas and hemarthrosis due to the severe FVIII deficiency.  

Diagnosis can be easily made by the absence of detectable VWF levels, accompanied by the deficiency in FVIII.  Patients with type 3 VWD do not respond to desmopressin therapy.  Therefore, substitution therapy with purified human VWF in conjunction with FVIII is the best preventative option for affected patients.

VWD is caused by mutations in the VWF gene.  Mutations in this gene lead to intracellular retention or rapid clearance of VWF from the circulation.  The level of VWF in blood group O is 25-35% lower than in non-O blood groups.  Therefore, individuals with blood group O are at a greater risk for developing VWD.