Table 3.

Procoagulant effects of inflammatory mediators

Inflammatory Mediator	Procoagulant effects
Proinflammatory cytokines	Increased TF expression on endothelium, monocytes; decreased TM and endothelial protein C receptor; increased PAI-1; release of TFPI from endothelium with loss of activity
Complement components	Decreased C1-esterase inhibitor leads to loss of contact factor regulation; damaged cell membranes promote procoagulant activity on cell surfaces of endothelial cells
Acute phase proteins	Increase in clotting factor synthesis; decrease in synthesis of antithrombin; α1-antitrypsin decreases APC and cleaves TFPI; CRP promotes TF expression; C4b-binding protein binds to protein S and limits protein C activity
Neutrophils	Elastase destroys antithrombin, C1-inhibitor, thrombomodulin, and cleaves TFPI; intravascular neutrophil–platelet aggregates occlude capillary beds
Activated monocytes	Upregulation of TF expression; IL-6 and TNF synthesis promote acute phase proteins with procoagulant activities; release of microvesicles with TF in circulation
Activated endothelium	P-selectin promotes platelet aggregation, procoagulant surface upregulation of TF; PAF expression stimulates platelets; shedding of glycosaminoglycans limits antithrombin binding; loss of TM and EPCR expression limits APC synthesis

APC, activated protein C; CRP, C reactive protein; EPCR, endothelial protein C receptor; PAF, platelet activating factor; PAI, plasminogen activator inhibitor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; TNF, tumor necrosis factor.