Figure 5

Inflammation-Coagulation Crosstalk and Extrinsic Pathway Activation in Majorly Depressed Suicide Attempters.

Inflammatory cytokines induce endothelial cells to express soluble TF. More potent upregulation of CRP and SAA1 in MDD-SA subjects induces increased monocytic expression of cell-bound TF, which catalyzes the conversion of increased soluble TF and circulating FVII to generate the TF-FVIIa complex that efficiently converts the increased FX to FXa. FXa and thrombin then mediate the activation of increased FV to form FVa, which, in turn, binds to FXa to form prothrombinase (FVa-FXa complex). TFPI upregulation indicates inhibition of the TF-FVIIa complex and FXa. PCI downregulation indicates disinhibition of FXa. APC upregulation is likely a result of PCI downregulation. The cumulative effect of these differential changes in protein expression yields increased relative prothombinase activity in MDD-SA relative to MDD-NA subjects (Fig. 6). Acronyms: MDD, major depressive disorder; MDD-SA, majorly depressed suicide attempter; MDD-NA, majorly depressed non-attempter; HC, healthy control; TNF-alpha, tumor necrosis factor-alpha; IL-1, interleukin-1; IL-6, interleukin-6; CRP, C-reactive protein; SAA1, serum amyloid A protein 1; TF, tissue factor; FVII, coagulation factor FVII; FVIIa, activated coagulation factor FVII; FX, coagulation factor X; FXa, activated coagulation factor X; FV, coagulation factor V; FVa, activated coagulation factor V; TFPI, tissue factor pathway inhibitor; PCI, protein C inhibitor; APC, activated protein C.