Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines

Abstract

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.

Keywords: coagulation; disseminated intravascular coagulation; guidelines; laboratory evaluation; sepsis; sepsis-induced coagulopathy.

Figure 1

The main pathogenetic mechanisms involved in sepsis. Following pathogen invasion, innate immune cells recognize antigens through pattern-recognition receptors (PRRs). Activated innate immune cells release cytokines and inflammatory mediators to activate lymphocytes and the coagulation cascade, resulting in sepsis-induced coagulopathy and disseminated intravascular coagulopathy. Moreover, damage-associated molecular patterns (DAMPs) activate complement, which also results in activation of the coagulation cascade.

Figure 2

Derangement of the hemostatic balance in sepsis includes hyperactivation of the coagulation process and suppression of the anticoagulant mechanisms such as fibrinolysis and release of anticoagulant factors.

Figure 3

Main mechanisms involved in hemostasis–inflammation cross talk. Pro-inflammatory mediators such as tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) are released by monocytes and macrophages to induce the coagulation cascade, while transmembrane receptors on monocytes can be activated by thrombin and other coagulation factors to trigger the release of pro-inflammatory cytokines. Moreover, antithrombin can directly bind to inflammatory cells and suppresses the expression of cytokine receptors, while also activated protein C downregulates endotoxin-induced production of cytokines by monocytes and macrophages.