Clinical Utility of Testing
Currently, the most significant impact of molecular testing on clinical management and genetic counseling is the differentiation of type 2N VWD and mild HA. Both have a mild to moderate reduction in F8 activity, with normal levels of VWF antigen and ristocetin cofactor activity. The autosomal inheritance pattern and the need for use of VWF concentrates rather than pure F8 concentrates make this an important distinction. Differentiation of VWD types 2A and 2B also provides useful information that alters clinical management. Although patients with type 2B VWD are characterized by the presence of variable degrees of thrombocytopenia, the differentiation from type 2A by platelet count is not always possible. The distinction between types 2A and 2B is clinically significant because treatment with vasopressin (DDAVP) is contraindicated in patients with type 2B due to the potential for worsening the thrombocytopenia.
Currently, for type 1 VWD patients, given the mild phenotype, the lack of well-characterized mutations, and the implication of locus heterogeneity, genetic testing is not useful. In contrast, type 3 VWD patients have well-characterized mutations and a severe phenotype. Genotyping the index patient would likely not affect clinical management; however, identification of the specific mutations is useful for genetic counseling and prenatal diagnosis.