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2013 Annual Minutes
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6/19/2013 at 8:44:24 PM GMT
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2013 Annual Minutes

Factor XI and the Contact System

Chairman: Thomas Renne (Sweden)

Co-Chairs: Jonas Emsley (UK), David Gailani (USA), Jose W. Govers-Riemslag (Netherlands), Christine Mannhalter (Austria), Joost Meijers (Netherlands), James Morrissey (USA), Ophira Salomon (Israel)

June 30, 2013

Summary of SSC meeting Factor XI and the contact system The factor XI and contact system was extremely well attended with 250 for the educational session and up to 400 in the main session. The educational session had three talks from jonas emsley, edward feener and james morrisey covering topics on the structure of contact factors, the role BK receptors in hereditary angioedema (fact or fiction), and polyphosphates in coagulation respectively. The subcommittee session contained seven talks on a variety of topics including the involvement of coagulation factor XII in fibrinolysis, the link to NETs, and studying FXI variants using next generation sequencing. The most well attended talks were the last two on new inhibitor developments targeting FXII and FXI for safer anticoagulation.

Structures of contact factors. Jonas Emsley. In the first part of the talk an overview of the domain structure for contact factors and FXI was presented and then data presented on a new structure of the FXI complex with a peptide from HK. Later information on the structure of the FXII protease domain and a review of old and new electron microscopy data on contact factors was also presented.

The contact system in diabetes. Dr Edward Feener . In the first part of the talk he showed the role of kallikrien in controlling intercerebral hemorrage in hyperglycaemic states. In the second part he was alluding to the activation of the contacts system and BK formation in diabetic retinopathy.

Polyphosphates in coagulation. Dr James morrisey presented an elegant overview of the polyphosphatees in coagulaton inlcuding the role of platelet polyphates in activating FXII, role in factor XI feedback activation by thrombin and function of the polymer in fibrinolysis.

Hereditary angioedema - facts and fiction. Eric Hack. Highlighted the role of the B1R receptor for increased vascular permeability in edema. He summarised studies on the relative importance of B2R versus B1R for targeting edema. The last part of his talk was on the role of inflammatory stimuli for local and systemic activation of the contact system.

Increased factor XIIa activity in patients on extracorporeal membrane oxygenation - a link to NETs. Simon Davidson. He gave a background of the clincial use of extracorproal circulation and summarised classical and new data showing activation of the contact system in ECMO. He discussed potential activators of the contact system in ECMO including NET formation and artifial surfaces.

The involvement of coagulation factor XII in fibrinolysis. Joke Konings. This talk summarised the recent blood paper on the crosstalk of the intrinsic pathway and fibrinolytic systems with implications for changes in the density of clot structure in the presence of FXII or FXIIa.

Understanding the role of sequence variation in the factor XI gene in the next- generation sequencing era. Stephano Duga. This talk outlined the new of new technologies in next generation sequence to pinpoint novel sequence variants and identify phenotypes.

FXI inhibitors. Eric Tucker. Summarised new data on different antibodies targeting FXIIa mediated FXI acitivation or FXIa. The FXI binding antibodies recognising FXI do not affect the thrombin feedback loop and selectively block the FXIIa activation of the intrinsic pathway. The FXI binding antibody that blocks FXIa cleavage of FIX has a more potent antithrombotic effects in a baboon model of thrombosis.

Factor XIIa inhibitors. Marc Nolte. A novel phage display based antibody interferes with FXIIa activity and FXIIa driven thrombus formation in mouse models of thrombosis and anterial venous shunt systems in rabbits. This recombinant monoclonal is in a stage 4 clinical trial in humans.

Last edited Thursday, July 11, 2013
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