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Effect of Platelet-Derived β-thromboglobulins on Coagulation

Effect of Platelet-Derived β-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, Johan W M Heemskerk, Fionnuala Ní Áinle

Thromb Res. 2017 Jun;154:7-15.

PMID: 28384443

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.
Aim/methods:
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.
Conclusion:
βTG modulate coagulation in vitro via an interaction with factor X.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4246521	Thrombin generation chromogenic substrate			Price

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