Effect of platelet-derived beta-thromboglobulins on coagulation

Karl Egan, Johanna P. van Geffen, Hui ma, Barry Kevane, Aine Lennon, Seamus Allen, Elaine Neary, Martin Parsons, Patricia Maguire, Kieran Wynne, Richard O' Kennedy, JohanW. M. Heemskerk, Fionnuala Ni Ainle*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Background: beta-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived beta-thromboglobulins (beta TG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of beta TG on coagulation is unknown.

Aim/Methods: Clotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified beta TG on coagulation.

Results: In normal pooled plasma, beta TG shortened the lagtime and time to peak thrombin generation of tissue factor (TF)-dependent and TF-independent thrombin generation. In factor VIII and factor IX-deficient plasmas, beta TG induced thrombin generation in the absence of a TF stimulus and in the presence of anti-TF and factor VIIa inhibitory antibodies. The procoagulant effect was not observed when thrombin generation was independent of factor X activation (supplementation of factor X-deficient plasma with factor Xa). Cleavage of a factor Xa-specific chromogenic substrate was observed when beta TG was incubated with factor X, suggesting a direct interaction between beta TG and factor X. Using SPR, beta TG were found to bind to immobilised factor X in a dose dependent manner.

Conclusion: beta TG modulate coagulation in vitro via an interaction with factor X. (C) 2017 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalThrombosis Research
Volume154
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Platelet-derived beta-thromboglobulins
  • Coagulation
  • Thrombin generation
  • Factor X
  • PEPTIDE CTAP-III
  • ACTIVATED PROTEIN-C
  • THROMBIN GENERATION
  • CXC CHEMOKINES
  • HEMOPHILIA-A
  • FACTOR-XA
  • TISSUE
  • PLATELET-FACTOR-4
  • LOCALIZATION
  • INACTIVATION

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