Structure and Function of Recombinant versus Plasma-Derived von Willebrand Factor and Impact on Multimer Pharmacokinetics in von Willebrand Disease

• DOI: 10.2147/jbm.s377126
• Publication Date: 2022-11-14T04:20:13Z
• Authors: Herbert Gritsch; Gerald Schrenk; Nina Weinhappl; Björn Mellgård; Bruce Ewenstein; Peter L Turecek
• Keywords: von Willebrand Disease; ADAMTS13; Ristocetin

Recombinant von Willebrand factor (rVWF, vonicog alfa) is a purified VWF concentrate produced from Chinese hamster ovary cells. rVWF not exposed to the VWF-cleaving protease ADAMTS13 and so subject proteolytic degradation of large (L) ultra-large (UL) multimers by that enzyme.To compare structure function with human plasma-derived [pdVWF] concentrates Haemate P®/Humate-P®, Voncento®, Wilate®/Eqwilate®, Wilfactin®/Willfact®; investigate relationship between multimeric pattern VWF:ristocetin cofactor (VWF:RCo) activity through population pharmacokinetic (PK) modeling in patients severe disease (VWD) treated rVWF.Analyses included VWF:RCo activity, VWF:collagen-binding VWF:platelet glycoprotein Ib receptor binding, VIII (FVIII) binding capacity, VWF-mediated platelet adhesion under flow conditions. was determined agarose gel electrophoresis. Population PK models describing activity-time profile small, medium, L/UL following intravenous administration VWD were developed.Findings demonstrate contains non-degraded multimer including UL present pdVWF concentrates. displayed higher specific platelet-binding faster mediation collagen shear stress versus also demonstrated FVIII capacity than P®, Voncento® Wilate®. Modeling provided evidence associated circulation.Findings suggest L preserved contribute high biological might be important for providing hemostatic efficacy.