title: Effect of platelet-derived β-thromboglobulins on coagulation.
abstract: BACKGROUND
  β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) 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 βTG on coagulation is unknown.
  
  
  OBJECTIVE
  Clotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified βTG on coagulation.
  
  
  RESULTS
  In normal pooled plasma, βTG 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, βTG 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 βTG was incubated with factor X, suggesting a direct interaction between βTG and factor X. Using SPR, βTG were found to bind to immobilised factor X in a dose dependent manner.
  
  
  CONCLUSIONS
  βTG modulate coagulation in vitro via an interaction with factor X.
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Ireland; Conway Institute, University College Dublin, Ireland.
authors.forename: Karl
authors.initials: K
authors.lastname: Egan
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Johanna P
authors.initials: JP
authors.lastname: van Geffen
authors.affiliation: School of Biochemistry & Biomedical Diagnostics Institute, Dublin City University, Ireland.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Ireland; Conway Institute, University College Dublin, Ireland; Department of Haematology, Rotunda Hospital, Dublin, Ireland.
authors.forename: Barry
authors.initials: B
authors.lastname: Kevane
authors.affiliation: Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Aine
authors.initials: A
authors.lastname: Lennon
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Ireland; Conway Institute, University College Dublin, Ireland.
authors.forename: Seamus
authors.initials: S
authors.lastname: Allen
authors.affiliation: Department of Neonatology, Rotunda Hospital, Dublin, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Neary
authors.affiliation: Conway Institute, University College Dublin, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Conway Institute, University College Dublin, Ireland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Maguire
authors.affiliation: Conway Institute, University College Dublin, Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: Wynne
authors.affiliation: School of Biochemistry & Biomedical Diagnostics Institute, Dublin City University, Ireland.
authors.forename: Richard
authors.initials: R
authors.lastname: O' Kennedy
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Johan W M
authors.initials: JWM
authors.lastname: Heemskerk
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Ireland; Conway Institute, University College Dublin, Ireland; Department of Haematology, Rotunda Hospital, Dublin, Ireland; Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland. Electronic address: fniainle@mater.ie.
authors.forename: Fionnuala Ní
authors.initials: FN
authors.lastname: Áinle
mesh_terms: D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism; D005170:Factor X / Q000378:metabolism*; D006801:Humans; D015539:Platelet Activation; D060066:Protein Interaction Maps; D011994:Recombinant Proteins / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D001620:beta-Thromboglobulin / Q000378:metabolism*
chemical_list: D001779:Blood Coagulation Factors; C061615:PPBP protein, human; D011994:Recombinant Proteins; D001620:beta-Thromboglobulin; D005170:Factor X; D013917:Thrombin
keywords: Coagulation; Factor X; Platelet-derived β-thromboglobulins; Thrombin generation