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2014 Annual Minutes
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6/18/2014 at 3:37:31 PM GMT
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2014 Annual Minutes
Factor XI and the Contact System
 

Chairman: Jonas Emsley (UK)
Co-Chairmen: Jose Govers-Riemslag (the Netherlands), Christine Mannhalter (Austria), Joost Meijers (Netherlands), James Morrissey (USA), Thomas Renne (Sweden), Ophira Salomon (Israel)
 
Thursday, 26 June (8:45-12:45)
 
Owen McCarty –  (Portland, USA) FXI activation and the virulence of infectious agents - The presentation of the cleavage of TFPI by factor XIa further defining the nature of the the pathway leading to thrombosis as opposed to hemostasis.
 
Ricky Travers –  (Urbana, USA) Visualizing polyP in thrombi and using novel anti-polyP compounds to stop thrombosis. This showed imaging of polyP emerging from cells and  described data on compounds capable of binding to polyP and inhibiting thrombosis with minimal bleeding risk.
 
Thomas Renné – (Karolinska Stockholm, Sweden) Factor XII function in thrombosis and hemostasis This was a description of the use of an antibody 3F7, which bound to the FXII protease domain. It was shown to to thromboprotection in extracorporeal circulation without increasing bleeding risk.
 
Evi Stavrou – (Cleveland, USA) Contact Activation Murine KOs: Unexpected Findings When Characterizing Mechanisms Related to Thrombosis Protection. This talk described contact system independent functions of plasma kallikrein.
 
Coen Maas – (Utrecht, the Netherlands) Plasmin triggers proteolytic Factor XII activation on endothelial cells, which is accelerated by the lysine substitution T328K that causes type III angioedema. This presentation detailed a new mechanism for the activation og mutant FXII.
 
Judith Cosemans – (Maastricht, the Netherlands) Factor XII regulates the pathological process of thrombus formation on ruptured plaques. This talk described novel in vivo functions of FXII for plaque-driven thrombosis and show FXII to contribute to thrombus stability.
 
Elaine Gray – (NIBSC, Potters Bar, UK) An International Standard for Activated Factor XI (FXIa). A standard was presented on FXIa in response to problems with immunoglobulin preparations being linked to thrombosis due to contact protein contamination in purification of immunoglobulins . This described an indirect assay involving FIX and FX and a chromogenic readout of FXa production. Different laboratories utilised this technique and were able to show very similar results in quantifying FXIa. The SSC board recommended the adoption of this standard. As a comment at the meeting it was mentioned that immunogobulin preparations should all be tested with this standard together with FXI replacement therapy.
 
Theme: Inhibitors of FXI and the contact system: Safer anticoagulation
 
Umesh Desai – (Richmond, USA) Allosteric inhibitors of FXIa. This described compounds which allosterically inhibit FXIa activity by binding to the anion binding exosite in the protease domain. The first part described the discovery and characterisation which was published and subsequent part of th
 
Jon Kennisten – (Burlington, USA) – Discovery and characterization of a highly specific antibody inhibitor of plasma kallikrein. This talk described a crystal structure of an inhbitory antibody Fab fragment bound to the protease domain of kallikrein. This antibody is in clinical trials for the treatment of edema.
 
Rebecca Smock –  (Seattle, USA) - Inhibiting the contact pathway with RNA aptamers . This was a very elegant presentation and in the first part published data was described showing nucleic acid aptamers which bind to FXII and inhibit its activity. The pattern of inhibition inhibited contact activation as measured by FXII activity varied based on which activator is used. In the second part of the talk new data aptamers which inhibit FXI
 
Vladimir Kolyadko – (Russia) Characterisation and development of factor XIIa inhibitors for assaying tissue factor triggered coagulation. TOP ABSTRACT. This presentation described the effect of corn trypsin inhibitor CTI on various assays.   Open discussion
 
Joost Meijers – José Govers-Riemslag (the Netherlands) Polyphosphates and activation of the contact system. Is the contact system involved in both arterial and venous thrombosis? Joost Meijers, Amsterdam, and José Govers-Riemslag, Maastricht, introduced a new addition to the SSC session with an open discussion. The audience was allowed to vote on several questions with controversial opinions that dealt with two topics : 1). Polyphosphates and activation of the contact system, and 2). Is the contact system involved in both arterial and venous thrombosis? With active audience participation, the lively discussion reviewed relevance of platelet polyphosphates for activation of the contact system ex vivo and in vivo. The discussion on the relevance of the contact system for thrombosis gave the consensus that murine data support roles of factors XI and XII in both venous and arterial thrombosis, but that the roles of the factors in especially venous thrombosis in humans needs to be further investigated.


Last edited Thursday, September 25, 2014
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