Binding of plasma factor XIII to thrombin-receptor activated human platelets

Béla Nagy Jr; Zsuzsa Simon; Zsuzsa Bagoly; László Muszbek; János Kappelmayer

doi:10.1160/TH09-01-0054

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(01): 83-89
DOI: 10.1160/TH09-01-0054

Platelets and Blood Cells

Schattauer GmbH

Binding of plasma factor XIII to thrombin-receptor activated human platelets

Béla Nagy Jr

¹Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

,

Zsuzsa Simon

¹Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

,

Zsuzsa Bagoly

²Clinical Research Center and Thrombosis, Haemostasis and Vascular Biology Research Group, Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

,

László Muszbek

²Clinical Research Center and Thrombosis, Haemostasis and Vascular Biology Research Group, Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

,

János Kappelmayer

¹Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

› Author Affiliations

Abstract

Summary

Platelet-bound coagulation factor XIII (FXIII) is targeted and concentrated at the site where platelet-rich thrombi are formed. Previous studies were in disagreement about the nature of FXIII binding to platelets. In this study, thrombin-receptor activating peptide (TRAP)-stimulated human whole blood and washed platelets were analysed by flow cytometry for the binding of FXIII using a monoclonal antibody against the A subunit of FXIII (FXIII-A). Here, we demonstrate that FXIII-A positivity significantly increased on activated platelets in whole blood compared to unstimulated sample, but not in washed platelets. GPIIb/IIIa receptor plays an essential role in FXIII binding, as fibrinogen receptor antagonist eptifibatide and fibrinogen binding inhibitor RGDS tetrapeptide significantly prevented the binding of FXIII. Furthermore, stimulated platelets from a patient with severe type I Glanzmann thrombasthenia showed insignificant FXIII-A positivity versus healthy controls. In addition, basal negligible amount of FXIII on washed platelets was only slightly increased when highly purified plasma FXIII (FXIII-A²B²) was added upon platelet activation by TRAP. Similarly, no remarkable FXIII-A positivity was observed when we used FXIII-A²B² with γA/γA fibrinogen. However, γA/γ' fibrinogen significantly augmented FXIII binding on TRAP-stimulated platelets in the presence of non-activated FXIII-A²B². We conclude that FXIII-A²B² of plasma origin binds to thrombin-receptor activated platelets via GPIIb/IIIa receptor-bound fibrinogen with γ’-chain and is not capable of direct platelet binding.

Keywords

Factor XIII - platelet activation - TRAP - fibrinogen

Full Text

References

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