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Factor VIII-related antigen (vWAg I) is a protein of high molecular weight which co-purifies with Factor VIII procoagulant activity and von Wiflebrand Factor under a variety of conditions. It is decreased or absent in most cases of von Willebrand’s disease (vWD). We now report the existence of a second antigen (vWAgII) which is absent from the plasma of individuals (3/3) with severe vWD but present in normal amounts in the plasmas of individuals (8/8) with moderate or variant vWD. vWAgII is present in normal platelets and is released from them during clotting. However, it is also present in platelet-free plasma from normal individuals which has been collected in a variety of protease inhibitors including benzamidine, heparin, Trasylol, PMSF and soybean trypsin inhibitor suggesting that it circulates in plasma in vivo. The plasma from a patient with intravascular coagulation was found to have increased vWAgII.  vWAgII is detected by antisera raised against void volume fractions of American Red Cross Factor VIII concentrates subjected to agarose gel chromatography. Antisera raised against highly purified vWAgI do not detect vWAgII. Crossed immunoelectrophoretic analysis shows vWAgII to have a more anodic mobility than vWAg I. II exhibits no immunologic cross-reactivity with intact vWAgI nor with vWAg I fragments produced by plasmin, a-chymotrypsin, trypsin or elastase. Though the absence of both antigens from the plasma of individuals with severe vWD suggests a biologic linkage, immunologic evidence for the origin of these two species from a common precursor has not been demonstrated.

vWAgII: A New von Willebrand’s Disease Antigen