Blood Coagulation as an Intrinsic Pathway for Proinflammation: A Mini Review

Abstract

Blood coagulation could be recognized as intrinsic inflammation. The coagulant mediators (FVIIa, FXa, thrombin (FIIa), FXIIa) and fibrin(ogen) activate cellular signaling, eliciting the production of cytokines, chemokines, growth factors, and other proinflammatory mediators. Hypercoagulability with elevated coagulant mediators would certainly trigger hyper-inflammatory state not to mention about the direct hypercoagulable actions on thrombosis, and platelet and complement activations, all of which contribute to inflammatory events. Furthermore, anticoagulant's anti-inflammatory effects readily reinforce the proposal that blood coagulation results in inflammation. The observations on protease activated receptor (PAR) activation and PAR antagonists modulating inflammation are also in line with the concept of coagulation-dependent inflammation.

Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

“…n severe viral infections and sepsis, as for bacterial sepsis, there is high associated mortality, up to 40 to 70%, in viral infections where treatment is very limited (1)(2)(3)(4)(5)(6)(7)(8). Once a patient is in shock, treatment options are often restricted to hemodynamic support.…”

“…Once a patient is in shock, treatment options are often restricted to hemodynamic support. In septic states, widespread intravascular clotting and hemorrhage called disseminated intravascular coagulation (DIC) can occur, leading to microvascular thrombosis, organ damage, and shock (1)(2)(3)(4)(5)(6)(7)(8). The excessive clot formation depletes coagulation factors, which, in turn, can cause excess bleeding (consumptive coagulopathy).…”

“…The excessive clot formation depletes coagulation factors, which, in turn, can cause excess bleeding (consumptive coagulopathy). Activation of thrombotic and thrombolytic proteases and also inflammatory responses is reciprocal (1)(2)(3)(4)(5)(6)(7)(8)(9). With dysregulated coagulation, there is massive upregulation of cytokines and other inflammatory mediators.…”

“…With dysregulated coagulation, there is massive upregulation of cytokines and other inflammatory mediators. This cytokine storm contributes to tissue damage, producing leaky capillaries (permeable blood vessels) and increasing virulence with, in some cases, dysfunctional immune responses (1)(2)(3).…”

“…These approaches have produced only moderate (6 to 19%) reductions in death rates (5)(6)(7)(8)(9)(10)(11). Anti-inflammatory approaches, such as interleukin 10 (IL-10), for treatment of sepsis have also been tested, again with variable success in clinical trials (1)(2)(3)(4)(5)(6)(7)(8). Additionally, low levels of protease activation, as in cancer and infection, can influence innate immune responses without overt coagulopathic or hemorrhagic changes.…”