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 language | English |
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Pages (from-to) | 7-15 |
Number of pages | 9 |
Journal | Thrombosis Research |
Volume | 154 |
DOIs | |
Publication status | Published - 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