Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis

Blood. 2013 Dec 12;122(25):4107-10. doi: 10.1182/blood-2013-04-496851. Epub 2013 Oct 8.


Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (>50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / biosynthesis
  • ABO Blood-Group System / chemistry
  • ADAM Proteins / chemistry*
  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAMTS13 Protein
  • Blood Coagulation / physiology
  • Blood Platelets / chemistry*
  • Blood Platelets / cytology
  • Blood Platelets / metabolism
  • Gene Expression Regulation
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Platelet Activation / physiology
  • Proteolysis*
  • Secretory Vesicles / chemistry*
  • Secretory Vesicles / metabolism
  • von Willebrand Factor / chemistry*
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism


  • ABO Blood-Group System
  • von Willebrand Factor
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human