What are variants of von Willebrand disease (vWD)?

Updated: Nov 30, 2019
  • Author: Perumal Thiagarajan, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

Answer

Although the common form of von Willebrand disease (type I) results from a quantitative deficiency of vWf, the variants result from qualitative abnormalities in the von Willebrand protein.

A common variant (type IIA) of von Willebrand disease results from functionally defective vWf that is unable to form multimers or be more susceptible to cleavage by ADAMTS13. Larger multimers are more active in mediating platelet vessel-wall interaction. In these variants, the factor VIII level may be normal.

In the type IIB variant, the von Willebrand protein has heightened interaction with platelets, even in the absence of stimulation. Platelets internalize these multimers, leading to a deficiency of von Willebrand protein in the plasma.

The type IIN (Normandy variant) is caused by defect in vWf to bind coagulation factor VIII, resulting in the shortened half-life of factor VIII in the plasma. The ristocetin-induced platelet aggregation and vWf antigens are normal. Previous descriptions of autosomal recessive hemophilia A are most likely von Willebrand disease type IIN.

Type IIM von Willebrand disease is due to a defect in binding to platelet glycoprotein Ib but no defect in multimerization. In this variant, the ristocetin cofactor activity and ristocetin-induced platelet aggregation are decreased but the vWf antigen and multimers are present in normal levels.

A disorder of platelet GP Ib, mimicking type IIB von Willebrand diseas, has also been described. In this condition, increased affinity for von Willebrand protein in the resting stage leads to the deletion of plasma von Willebrand protein. This disease is called pseudo von Willebrand disease or platelet-type von Willebrand disease.

Type III von Willebrand disease is a severe form that is characterized by very low levels of vWf and clinical features similar to hemophilia A, but with autosomal recessive inheritance. This condition results from a homozygous state or double heterozygosity.


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