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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
1   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
,
Zsuzsa Simon
1   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
,
Zsuzsa Bagoly
2   Clinical 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
2   Clinical 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
1   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
› Author Affiliations
Further Information

Publication History

Received: 22 January 2009

Accepted after minor revision: 14 March 2009

Publication Date:
24 November 2017 (online)

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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
 

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