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A von Willebrand Factor Fragment Containing the D'D3 Domains is Sufficient to Stabilize Coagulation Factor VIII in Mice

Yee A, et al., 124(3):445-52, Blood, 2014

This article reports the effect of a series of von Willebrand factor (VWF) fragments on plasma factor VIII (FVIII) binding in vitro as well as their effect in vivo using mouse models. Typically, FVIII and VWF circulate together as a complex preventing FVIII from degradation and rapid clearance from plasma. The results indicate that a fragment containing only about 20% of the VWF sequence is sufficient to support FVIII stability in vivo. Binding assessments performed using an Octet RED system suggested that VWF propeptide processing of VWF D'D3 fragment is still a requirement for optimal FVIII affinity. Immobilized onto anti-FLAG biosensors, the VWF fragments (purified from transiently transfected HEK293T cells) allowed analysis of the association and dissociation of various concentrations of recombinant FVIII during these assays.

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