STUDIES OF MULTIMERIN IN PATIENTS WITH VON-WILLEBRAND DISEASE AND PLATELET VON-WILLEBRAND-FACTOR DEFICIENCY

In normal platelet alpha-granules von Willebrand factor (VWF) is store d with multimerin and factor V in an eccentric electron-lucent zone. B ecause the platelet stores of VWF are deficient in 'platelet low' type 1 and type 3 von Willebrand disease (VWD), we investigated their elec tron-lucent zone proteins. The patients with VWD had partial to comple te deficiencies of plasma and platelet VWF but normal alpha-granular m ultimerin and factor V, and normal alpha-granular fibrinogen, thrombos pondin-1, fibronectin, osteonectin and P-selectin. In type 3 VWD plate lets, alpha-granular electron-lucent zones lacking VWF-associated tubu les were identified and multimerin was found in its normal alpha-granu lar location, These findings indicate that the formation of the electr on-lucent zone and the sorting of multimerin to this region occur inde pendent of VWF. The isolated abnormalities in VWF suggests a VWF gene mutation is the cause of 'platelet low' type 1 VWD.