Recall that VWF is found in the circulation (bound to factor VIII) and within the alpha granules of platelets. Platelet VWF makes up only 10% of the VWF in blood. It reflects VWF synthesis by bone marrow megakaryocytes. VWF activity is typically measured using platelet activity assays and latex agglutination assays. However, there are also assays that measure VWF levels (rather than activity). These are referred to as 'antigen assays.' These assays also use latex immunoagglutination, but instead of relying on the patient's VWF to mediate the agglutination, the antigen assays mix patient plasma with latex particles that are coated with antibodies against VWF. The assay can then quantitate the amount of VWF present (though this assay does not assess whether the VWF is functional).
If the factor VIII, VWF antigen, and VWF activity are normal, and the ratio of VWF activity to VWF antigen is >0.8, Von Willebrand's disease is ruled out.
If the VWF activity assay is <55%, a VWF ristocetin cofactor activity assay is recommended. If the VWF antigen is <55%, VWF activity is <55%, or VWF activity:VWF antigen ratio is <0.8, then VWF multimer analysis can be performed, and a specific VWD diagnosis can be given.
