Abstract
Coagulopathy is common in acute sepsis and may range from subclinical activation of
blood coagulation (hypercoagulability), which may contribute to venous thromboembolism,
to acute disseminated intravascular coagulation, characterized by widespread microvascular
thrombosis and consumption of platelets and coagulation proteins, eventually causing
bleeding. The key event underlying this life-threatening complication is the overwhelming
inflammatory host response to the pathogen leading to the overexpression of inflammatory
mediators. The latter, along with the microorganism and its derivatives drive the
major changes responsible for massive thrombin formation and fibrin deposition: (1)
aberrant expression of tissue factor mainly by monocytes-macrophages, (2) impairment
of anticoagulant pathways, orchestrated by dysfunctional endothelial cells (ECs),
and (3) suppression of fibrinolysis because of the overproduction of plasminogen activator
inhibitor-1 by ECs and thrombin-mediated activation of thrombin-activatable fibrinolysis
inhibitor. Neutrophils and other cells, upon activation or death, release nuclear
materials (neutrophil extracellular traps and/or their components such as histones,
DNA, lysosomal enzymes, and High Mobility Group Box-1), which have toxic, proinflammatory
and prothrombotic properties thus contributing to clotting dysregulation. The ensuing
microvascular thrombosis–ischemia significantly contributes to tissue injury and multiple
organ dysfunction syndromes. These insights into the pathogenesis of sepsis-associated
coagulopathy may have implications for the development of new diagnostic and therapeutic
tools.
Keywords
infection - coagulation - fibrinolysis - neutrophil extracellular traps - microvascular
thrombosis
