We use necessary cookies to make our website work. We also use optional statistical, functional and marketing cookies that you can choose to decline in your preference setting. For more information about the use of cookies or our use of data, see our Cookies notice or Privacy notice

Cookies settings I agree I refuse

Cookies information

Our site uses tools, such as cookies, to analyze and improve your experience. You can unsubscribe below:

Statistics

We use tools, such as Google Analytics, to track web traffic and verify the effectiveness of our site.

Necessary

Cookies required for essential services and features such as login forms, shopping cart integration and access control. Without them, our website cannot function properly and we cannot provide any services. Deactivation is not available.

These settings will be kept for 24h

Publications

Ir-CPI: an original inhibitor of thrombosis and thrombosis-associated with cancer

Ir-CPI: an original inhibitor of thrombosis and thrombosis-associated with cancer
Publications
Ir-CPI: an original inhibitor of thrombosis and thrombosis-associated with cancer

Abstract ISTH SSC 2018

Roxane DarboussetA, Valérie PireauxB, Lydie CrescenceC, Stéphanie DemoulinB, Laurence Panicot-DuboisC, Edmond GodfroidC, Christophe DuboisB

  • A
    The University of Sydney, Heart Research Institute, Sydney, Australia
  • B
    Bioxodes, Marche-en-Famenne, Belgium
  • C
    Aix-Marseille University, Center for CardioVascular and Nutrition Research, Marseille, France

Documents

Poster

Background

Ir-CPI, a protein derived from saliva of the tick Ixodes ricinus, is an inhibitor of the activated form of factor XI (FXIa) and XII (FXIIa). In vitro, this molecule inhibits specifically the contact phase pathway.

Aims

Our aims were to assess the efficacy of Ir-CPI in the prevention of thrombosis dependent on the Tissue Factor (TF) pathway in mouse models of thrombosis.

Methods

Two thrombosis models dependent on TF activation were studied. First, we used a laser-injury model on a cremaster muscle arteriole that is strictly dependent on TF and independent of FXII. Second, we used a laser-induced thrombosis model in mice bearing a pancreatic tumor. This model is mainly dependent on TF expressed by cancer cell-derived microparticles. As control, we assessed the efficacy of Ir-CPI in the Deep Vein Thrombosis (DVT) model in which FXII plays a central role in thrombus formation.

Results

As expected, Ir-CPI significantly reduced thrombus weight in the DVT model. Surprisingly, Ir-CPI inhibited thrombus formation, platelet accumulation and fibrin generation in the laser-injury model in normal mice. The effects of Ir-CPI on thrombosis were confirmed in tumor-bearing mice despite their procoagulant state. Since neutrophils play a key role in the activation of the TF dependent pathway in the laser model, the presence and activation of neutrophils were compared in control and Ir-CPI-treated mice. In vivo, Ir-CPI significantly inhibited neutrophil accumulation and their secretion of Neutrophil Elastase at the site of injury. In vitro, Ir-CPI strongly diminished the activation of neutrophils leading to NETs formation.

Conclusion

As expected, Ir-CPI is an effective antithrombotic in the FXII-dependent mouse model. Surprisingly, it is effective in a laser-injury model, even in a prothrombotic tumoral state. The inhibitory effect on neutrophil recruitment in vivo and NETs formation in vitro strongly suggests that Ir-CPI has additional targets and offers new therapeutic opportunities in thrombosis-associated diseases.