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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalThrombosis and Haemostasis
Volume102
Issue number1
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Thrombin Receptors
Factor XIII
Blood Platelets
thrombin receptor peptide SFLLRNP
Fibrinogen
Platelet Glycoprotein GPIIb-IIIa Complex
Fibrinogen Receptors
Thrombasthenia

Keywords

  • Factor XIII
  • Fibrinogen
  • Platelet activation
  • TRAP

ASJC Scopus subject areas

  • Hematology

Cite this

Binding of plasma factor XIII to thrombin-receptor activated human platelets. / Nagy, B.; Simon, Zsuzsa; Bagoly, Z.; Muszbek, L.; Kappelmayer, J.

In: Thrombosis and Haemostasis, Vol. 102, No. 1, 07.2009, p. 83-89.

Research output: Contribution to journalArticle

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