Congenital von Willebrand disease type 3: clinical manifestations, pathophysiology and molecular biology.

von Willebrand disease type 3 is the most severe form of this condition. Patients present with a moderate-to-severe bleeding tendency. The plasma von Willebrand factor level in these patients is very low or undetectable. Although rare, von Willebrand disease type 3 is of major interest because of its severe clinical presentation, the need for replacement therapy and the risk of occurrence of alloantibodies after the infusion of plasma concentrates. The inheritance of type 3 disease is typically autosomal recessive. The parents are often consanguineous, although compound heterozygous inheritance does occur. The molecular basis of von Willebrand disease type 3 has recently been studied in detail, several molecular defects being identified. This chapter will focus on the clinical and molecular aspects of type 3 von Willebrand disease.