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

Thromb Haemost. 2009 Jul;102(1):83-9. doi: 10.1160/TH09-01-0054.


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-A(2)B(2)) was added upon platelet activation by TRAP. Similarly, no remarkable FXIII-A positivity was observed when we used FXIII-A(2)B(2) with gammaA/gammaA fibrinogen. However, gammaA/gamma' fibrinogen significantly augmented FXIII binding on TRAP-stimulated platelets in the presence of non-activated FXIII-A(2)B(2). We conclude that FXIII-A(2)B(2) of plasma origin binds to thrombin-receptor activated platelets via GPIIb/IIIa receptor-bound fibrinogen with gamma'-chain and is not capable of direct platelet binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation / physiology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cytosol
  • Eptifibatide
  • Factor XIII / metabolism*
  • Fibrinogen / metabolism
  • Humans
  • Oligopeptides / pharmacology
  • P-Selectin / metabolism
  • Peptide Fragments / metabolism*
  • Peptides / pharmacology
  • Plasma
  • Platelet Activation / drug effects
  • Platelet Activation / physiology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Thrombasthenia / blood*


  • Oligopeptides
  • P-Selectin
  • Peptide Fragments
  • Peptides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • fibrinopeptides gamma
  • thrombin receptor peptide SFLLRNP
  • Fibrinogen
  • Factor XIII
  • arginyl-glycyl-aspartyl-serine
  • Eptifibatide