Contact system revisited: an interface between inflammation, coagulation, and innate immunity

Abstract

Summary. The contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role for host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that inorganic polyphosphate found in platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental studies have shown that interference with FXII provides thromboprotection without a therapy-associated increase in bleeding, renewing interest in the FXIIa-driven intrinsic pathway of coagulation as a therapeutic target. This review summarizes how the contact system acts as the cross-road of inflammation, coagulation, and innate immunity.

Peptide Macrocycle Inhibitor of Coagulation Factor XII with Subnanomolar Affinity and High Target Selectivity

“…4 Several in vivo activators of the plasma contact system were reported, including platelet and bacterial polyphosphates, extracellular RNA and DNA, amyloid β peptide and misfolded proteins. 1 FXII also constitutes a constant threat in medical procedures that depend on extracorporeal circulation such as cardiopulmonary bypass surgery, extracorporeal membrane oxygenation (ECMO), or hemodialysis. 7,8 In these procedures, contact with the materials of the medical devices, such 4 as tubing and membranes, can activate FXII and trigger the coagulation and inflammation pathways.…”

“…1 It is expressed as an 80 kDa zymogen, primarily by hepatocytes, and circulates in plasma at a concentration of around 0.4 µM. FXII is converted into its activated form, FXIIa, by proteolytic cleavage between the heavy chain and the enzymatic light chain.…”

“…FXIIa has the capacity to cleave factor XI, initiating the intrinsic coagulation pathway, and plasma kallikrein, activating the kallikrein-kinin system. 1 Activated plasma kallikrein can reciprocally activate FXII, leading to rapid activation of the contact system. FXIIa can also trigger the complement and fibrinolytic systems.…”

Era of Bloodless Surgery: Spotlights on Hemostasic Materials and Techniques

“…In the process of fibrinolysis, the products of coagulation, so called fibrin clots are broken down, plasmin, activated form of plasminogen cuts the fibrin meshwork, and circulating fragments of thrombus are eliminated by proteases or by liver and kidney [8].…”

“…Hanyang Med Rev 2018 Mar;38(1): [3][4][5][6][7][8][9][10][11][12][13][14][15] have reciprocal action with other platelets and they undergo aggregation and adhesion process.…”