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Coagulation factor XII in thrombosis and inflammation
1Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands; and.
Blood
|February 28, 2018
Summary
Targeting factor XII (FXII) and polyphosphate offers protection against thromboembolic diseases and hereditary angioedema by modulating the contact system. This approach avoids disrupting essential hemostasis, presenting new therapeutic avenues.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Immunology
Background:
- Proinflammatory and procoagulant reactions are central to cardiovascular disorders.
- The factor XII (FXII)-driven contact system initiates coagulation and inflammation.
- In vivo roles of the contact system are emerging, challenging traditional coagulation balance concepts.
Purpose of the Study:
- To review recent findings on the polyphosphate/FXII contact system.
- To explore its role at the intersection of procoagulant and proinflammatory states.
- To highlight therapeutic potential for thrombotic and inflammatory disorders.
Main Methods:
- Review of current literature on the contact system.
- Analysis of FXII and polyphosphate interactions.
- Investigation of in vivo functions versus in vitro biochemistry.
Main Results:
- Targeting FXII or polyphosphate prevents thromboembolic diseases without impairing hemostasis.
- The polyphosphate/FXII axis drives thrombus formation but is not essential for hemostasis.
- Excessive FXII activity is linked to hereditary angioedema.
Conclusions:
- The contact system, particularly the polyphosphate/FXII axis, is a key player in both thrombosis and inflammation.
- Interference with this system offers a promising strategy for treating diverse cardiovascular and inflammatory conditions.
- Elucidating the contact system opens avenues for developing safe therapeutic interventions.
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