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2015 Annual Minutes
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6/21/2015 at 3:16:24 PM GMT
Posts: 80
2015 Annual Minutes

Chairman:  Jonas Emsley

Co-Chairs:  Jose W. Govers-RiemslagChristine MannhalterJoost MeijersJames Morrissey,  Ophira SalomonEvi X. Stavrou

 

The factor XI and contact system was attended with 200 attendees

Bernd Engelmann (Germany):  Propagation of blood coagulation by extracellular nucleosomes/neutrophil extracellular traps was presented. This talk emphasised the importance of neutophils/platelets/contact system in thrombus formation.

particularly in venous thrombosis where FXIIa seems to be more important than neutophil elastase. This talk also showed the association of DNA from NETs with factor XII and DNA as an activator of the contact system.

Jonas Emsley (UK): Data on the structure of PK and the interaction with HK was presented together with

Ammar Majeed (Sweden): The Factor XII Registry Database. This talk reported a new website FXII registry website URL is (www.factor12.net) where patient information will be stored on FXII deficient. There are several reasons why this important. 1. There are few reports characterising factor XII deficient patients and currently no systematic collection of data. This is important as FXII is considered an important novel target for the treatment of thrombosis and yet there is no epidemiological data on the effects of deficiency in humans. This contrasts with the case of Factor XI where and established website is available and >200 cases of FXI deficiency have been characterised together with the genes sequenced. It was discussed that it would be beneficial to have sequencing carried out for the FXII genes and that patients with a defect but normal FXII plasma levels (CRM+) be entered into the database. The audience was encouraged to submit information on FXII deficient patients.

Nicola Mutch (UK): Driving plasminogen activation by factor XIIa. This talk described new data on FXII association fibrinolyisis - polyp modulated the fibrinolytic side of the FXIIa activity and polyp enhances fibrinolysis. PolyP binding characterised to FXII and plasminogen. The contribution of platelets to fibrinolysis was characterised as platelets secrete PolyP. PolyP accumulates in fibrin knots. A pathway was described for to contribute to fibrinolysis. FXII and fibrinogen were imaged localised on the surface of platelets at the cap with polyp.

Keith McCrae (USA): This talk presented an update on kininogen in thrombosis and stroke models and as an anti-angiogenic protein.

Toshitaka Sugi (Japan): Autoantibodies to FXII and kininogens in patients with recurrent pregnancy loss were described. This talk presented data on a series of FXII deficient patients characterised with recurrent pregnancy loss and also antibody interactions with FXII and kininogen in the present of phosphpolipid. A mechanism of FXII-antibody complexes with platelets is proposed for promoting thrombosis.

Theme: Inhibitors of FXI and the contact system: Safer anticoagulation

Maria Luiza Vilela Oliva (Brazil): Effect of plant inhibitors of the contact system on a mouse thrombosis model. CTI is a well know plant protein that is used as an inhibitor of the contact system. A further plan kunitz type inhibitor was presented which inhibits kallikirein and its properties were characterised as inhibiting thrombus formation in a mouse model. It was also proposed the inhibitor is bi-functional affecting the collagen receptor.

 

David Gailani (USA): New data were described for FXI anion binding sites and the effects of mutations here on PolyP and nucleic acid activation.

Sanjay Bhanot could not attend so David Gailani presented a second talk (USA): Antisense Reduction of FXI for Thromboprophylaxis: A Novel Therapeutic Approach. This data showed the first clinical trial of and antisense RNA targeting FXI (N Engl J Med. 2015 Jan 15;372(3):232-40.) This showed effective reduction in circulating FXI levels over a period of weeks such that thrombosis was mitigated with no bleeding side effect. Data on factor XI contribution to venous thromboembolism was also presented.

Open discussion José Govers-Riemslag (the Netherlands), and Joost Meijers, (the Netherlands), presented in an open discussion several topics to the audience. Since a factor XII registry was proposed, the first question was if each contact factor needs its own registry, which was nearly unanimously accepted. A combination of registries for the 4 contact proteins was found to be logistically unrealistic.

Furthermore, an inventory was made of the interest of the audience for the mechanisms that can be activated by the contact system. In order of interest, the audience voted for the coagulation system, the complement system, the kallikrein-kinin system and the fibrinolytic system. Finally, the development of assays for the contact system was discussed. A general test that could determine outcome of all the affected mechanisms was not found to be practical, but there was great interest in the design and execution of specific tests that could measure contact system mediated activation of the coagulation, kallikrein-kinin system, fibrinolytic system and complement system. The audience felt that there was a role for the SSC subcommittee in developing such assays.

 







Last edited Tuesday, August 18, 2015
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