Clotting and Inflammation
Clotting and inflammation are linked through crosstalk mechanisms. The two are in a highly integrated balance that in healthy circumstances optimizes our body's response to injury and infection. Dysregulation of any component can affect this balance, resulting in any number of illnesses rooted in inflammation. [a]
Clotting and Fibrinolysis
There is also a delicate balance between clot formation and clot breakdown (fibrinolysis). Out of balance on the clotting side we have unwanted clots, called thrombosis. Out of balance on the opposite spectrum can lead to bleeding.
We are going to focus on the clotting side of the balance, specifically to the fibrinogen molecule.
In response to injury or infection, a component called Tissue Factor (TF) becomes mobilized. TF joins clotting factors to create a blood clot, which is initially useful for the body to heal itself.
However, with extended exposure and sustained injury, the amount of thrombin generated can be amplified to exceed a threshold and promote platelet activation, thrombosis and inflammatory events that can lead to serious complications and death if left unchecked.
Undetected inflammation can also lead to debilitating chronic diseases that might be prevented and/or alleviated if we can identify and correct this underlying inflammation on time.
What role does Gamma Prime Fibrinogen play?
The fibrinogen subtype Gamma Prime Fibrinogen (GPF) creates chains that protect thrombin from inactivation. As GPF levels increase, clot size and durability increases both in the veins and the arteries. [b]
Clots made from GPF are tightly cross-linked and highly resistant to lysis by traditional strategies, such as heparin.
GPF is a superior biomarker for predicting thrombosis and inflammation, as well as allowing physicians make better treatment decisions.
a. Foley, JH and Conway, EM, Circulation Research 2016 b. Macrae et al., Blood Adv., 2021;5:3468