Linking inflammation and coagulation: novel drug targets to treat organ ischemia

Activation of the coagulation system during ischemia/reperfusion injury is an unavoidable event and even further augmented during cardiovascular surgery. Clotting not only leads to disturbance of blood rheology but also enhances the inflammatory response. We aim to highlight the inflammatory properties of the coagulation system and novel potential therapeutic approaches targeting both features.

Heparin, a thrombin inhibitor, is still the drug of choice for preventing coagulation following, for example, cardiovascular surgery. On the contrary, much effort is done to evaluate the utilization of direct thrombin inhibitors to prevent ischemia/reperfusion injury. Furthermore, targeting the inflammatory potential of the coagulation system seems to be very promising. Fibrin(ogen) and its degradation products modulate the inflammatory response, especially by inducing leukocyte migration. Inhibiting these pro-inflammatory effects, for example, by administration of Bβ15-42 was recently shown to be beneficial under various inflammatory conditions.

Ischemia and reperfusion are common activators of coagulation that is also accompanied by inflammation. Therefore, targeting this well orchestrated system might be of therapeutic benefit, as its mode of action is dual: clotting inhibition and anti-inflammation. This novel therapeutic approach might at least be of benefit in the treatment of systemic inflammatory syndromes following, that is, cardiovascular surgery.