What causes von Willebrand disease (vWD) type 2B?

Updated: Dec 30, 2019
  • Author: Eleanor S Pollak, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

vWD type IIB characterized by the loss of large multimers occurs through a mechanism distinct from that of type IIA. Observations to date have identified a critical region of vWF involved in the binding of vWF to the platelet receptor glycoprotein Ib (GpIb). Each of the identified single amino acid substitutions is thought to result in a gain of function, leading to spontaneous binding of vWF to platelets.

Normally, plasma vWF is inert in its interaction towards platelets until it encounters an exposed subendothelial surface. vWF binding to collagen and/or other ligands within the injured vessel wall presumably results in a secondary conformational change, which then facilitates binding to the GpIb receptor.

In vWD type IIB, the mutant vWF spontaneously binds to GpIb in the absence of subendothelial contact. The large multimers have the highest affinity for GpIb and are rapidly cleared from the plasma along with the bound platelets, resulting in thrombocytopenia and the characteristic loss of large multimers.


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