Platelet factor 4 inhibits ADAMTS13 activity and regulates the multimeric distribution of von Willebrand factor

Br J Haematol. 2020 Aug;190(4):594-598. doi: 10.1111/bjh.16553. Epub 2020 Mar 4.

Abstract

The efficiency of von Willebrand factor (VWF) in thrombus formation is related to its multimeric size, which is controlled by the protease ADAMTS13. However, it is not clear what regulates ADAMTS13 activity. In this study, we investigated whether PF4 could bind to VWF and inhibit ADAMTS13 activity. We found that PF4 binds to VWF and protects against ADAMTS13 activity. We also found that VWF-PF4 complexes circulate in patients with thrombotic thrombocytopenic purpura (TTP). Our data provides the first evidence that PF4 may have a novel role in regulating VWF multimers during primary haemostasis and thrombosis.

Keywords: ADAMTS13; platelet factor 4; platelets; thrombosis; von Willebrand factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / antagonists & inhibitors*
  • Hemostasis / physiology
  • Humans
  • Platelet Factor 4 / physiology*
  • Protein Binding
  • Protein Domains
  • Protein Interaction Mapping
  • Protein Multimerization
  • Proteolysis
  • Purpura, Thrombocytopenic, Idiopathic / blood*
  • Thrombosis / blood
  • von Willebrand Factor / analysis*
  • von Willebrand Factor / chemistry

Substances

  • PF4 protein, human
  • von Willebrand Factor
  • Platelet Factor 4
  • ADAMTS13 Protein
  • ADAMTS13 protein, human

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