Table 2.

The inflammatory effects of coagulation and loss of anticoagulants

Coagulation parameter	Proinflammatory Effects
Thrombin generation	Promotes cytokine and chemokine synthesis (IL-6, IL-8) via PARs, P-selectin, E-selectin and PAF expression, which facilitates neutrophil–endothelial cell interactions, bradykinin and histamine release
Factor Xa and TF–factor VIIa complex generation	Promotes cytokine and chemokine synthesis (IL-6, IL-8) via PAR-1 and PAR-2
Reduced antithrombin	Results in the loss of prostacyclin synthesis by endothelial cells, increased cytokine synthesis, increased leukocyte adherence and chemotaxis
Reduced protein C/protein S activity	Results in increased E-selectin expression, increased cytokine generation and neutrophil adherence; promotes apoptosis of endothelial cells
Reduced TFPI activity	Results in loss of regulation of cytokine synthesis within microcirculation
Platelet activation	Platelet derived P-selectin promotes neutrophil adherence, neutrophil–endothelial cell interactions; platelet CD40 ligand promotes endothelial cell chemokine and adhesion molecule expression; activated platelets secrete chemokines and IL-1β
Intravascular fibrin deposition	Neutrophil and monocyte adherence
Reduced thrombomodulin expression on endothelial cells	Loss of TM lectin domain activity that inhibits neutrophil–endothelial cell adherence may promote neutrophil binding

IL, interleukin; PAF, platelet-activating factor; PAR, protease activated receptor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin.