ABNORMAL COLLAGEN-BINDING ACTIVITY OF 2A VON-WILLEBRAND-FACTOR - EVIDENCE THAT THE DEFECT DEPENDS ONLY ON THE LACK OF LARGE MULTIMERS

It is well established that the large von Willebrand factor (vWf) mult imers bind with high affinity to the extracellular matrix. To explore the different roles of intermediate and large vWf multimers, we studie d the collagen-binding activity (vWf:CBA) of 2A vWf under nonflowing c onditions in relation to the multimer organization of the molecule. Re gardless of the anticoagulant used for blood collection, vWf:CBA was s ignificantly decreased, in 4 patients with 2A von Willebrand's disease (vWd), in accordance with the lack of high and intermediate vWf multi mers. After 1-deamino-8-D-arginine vasopressin (DDAVP) infusion, the a ppearance of circulating large and unusually large vWf multimers, in s amples collected in the presence of protease inhibitors, induced a com plete normalization of vWf:CBA. The peak was observed 15 minutes after DDAVP, when large and unusually large multimers were maximally repres ented. These effects were transient because vWf:CBA decreased after 60 minutes, even though values were still significantly higher than pre- DDAVP figures; at the same time, large vWf multimers appeared to be de creased. In contrast, samples anticoagulated with sodium citrate after DDAVP did not show a normalized vWf multimer pattern and were charact erized by a persistently decreased vWf:CBA. Moreover, in all of the pa tients studied, platelet vWf presented normal vWf:CBA values in accord ance with the normal levels and multimer organization of the vWf molec ule. Our findings indicate that the collagen-binding defect displayed in vitro by type 2A vWf depends only on the lack of circulating large vWf multimers. Moreover, the observation of normal platelet vWf:CBA se ems to indicate a primary role of plasma rather than platelet vWf in a ssuring platelet plug formation.