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Updated: Apr 21, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
von Willebrand factor is a cofactor in complement regulation
Shuju Feng1, Xiaowen Liang2, Michael H Kroll1
1Section of Benign Hematology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX;
Abstract:
Several complement proteins interact with hemostatic factors. We discovered that von Willebrand factor (VWF) acts as a cofactor for factor I-mediated cleavage of complement C3b, thereby shutting down complement activation. The complement regulatory function of VWF multimers depends on their size. Smaller VWF multimers enhance cleavage of C3b but large and ultra-large VWF (ULVWF) multimers have no effect on C3b cleavage and permit default complement activation. We conclude that normal plasma VWF multimers prevent complement activation and steer the complement pathway toward generation of inactivated C3b (iC3b). ULVWF multimers, as are present in patients with thrombotic microangiopathy, lack an inhibitory effect on complement and permit complement activation.
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