Pathophysiology of Sepsis-Induced Disseminated Intravascular Coagulation (DIC)

Key Pathophysiological Mechanisms

Sepsis initiates a systemic inflammatory response with release of inflammatory cytokines and mediators that convert the normally anticoagulant endothelium to a procoagulant state, according to the Nature Reviews Disease Primers 1, 3
Microorganisms and damage-associated molecular patterns (DAMPs) trigger the inflammatory cascade, activating complement and releasing inflammatory mediators, as reported by the Nature Reviews Disease Primers 1
Endothelial injury is a central component of sepsis pathophysiology, with disruption of tight junctions and conversion from anticoagulant to procoagulant properties, as stated in the Journal of Thrombosis and Haemostasis 3
Inflammatory cytokines damage the endothelium, exposing collagen fibers and activating von Willebrand factor (VWF), which further increases tissue factor expression, according to the Nature Reviews Disease Primers 2

Tissue factor pathway activation leads to thrombin generation, which converts fibrinogen to fibrin, resulting in widespread microvascular thrombosis, as reported by the Nature Reviews Disease Primers 2
The contact factor pathway is also activated through factor XII activation by negatively charged aggregates and activated platelets, according to the Nature Reviews Disease Primers 2

Sepsis causes dysfunction of three major anticoagulant pathways, including the antithrombin system 2, protein C pathway 4, and tissue factor pathway inhibitor (TFPI) 1
Endothelial dysfunction leads to decreased production and increased consumption of these natural anticoagulants, as stated in the Journal of Thrombosis and Haemostasis 3
Thrombomodulin (TM) expression is reduced on endothelial cells, impairing protein C activation, according to the Nature Reviews Disease Primers 1

Inflammatory cytokines increase plasminogen activator inhibitor-1 (PAI-1) activity, inhibiting tissue plasminogen activator (t-PA) and suppressing fibrinolysis, as reported by the Nature Reviews Disease Primers 2

Early stages of sepsis-induced coagulopathy show mild coagulation abnormalities with organ dysfunction, as stated in the Journal of Thrombosis and Haemostasis 5, 6
Advanced stages demonstrate widespread microvascular thrombosis, consumption of platelets and coagulation factors, and potential bleeding, according to the Journal of Thrombosis and Haemostasis 6
Laboratory findings typically include thrombocytopenia, prolonged prothrombin time, elevated D-dimer, and decreased fibrinogen in advanced cases, as reported by the Journal of Thrombosis and Haemostasis 6, 7

Angiopoietin-2 is released from Weibel-Palade bodies in endothelial cells during sepsis, inducing prothrombotic responses by expressing endothelial tissue factor and phosphatidylserine exposure, as stated in the Journal of Thrombosis and Haemostasis 3, 4
Angiopoietin-2 acts as an antagonist to the anti-inflammatory angiopoietin-1, increasing endothelial permeability and contributing to multiple organ dysfunction, according to the Journal of Thrombosis and Haemostasis 4