The coagulopathy of acute sepsis

Abstract

Purpose of Review Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in Disseminated Intravascular Coagulation (DIC). When present, DIC portends a higher mortality rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis will allow therapeutic interventions to be developed. The Coagulopathy of Acute Sepsis is a dynamic process that is time and disease burden specific. Whole blood testing of coagulation may provide more clinically useful information than classical tests. Natural anticoagulants that regulate thrombosis are down regulated in sepsis. Patients may benefit from modulation of the coagulation system when systemic inflammation and hypercoagulopathy exist. Proper timing of anticoagulant therapy may ultimately lead to decreased incidence of multisystem organ dysfunction (MODS). Recent Findings The pathogenesis of coagulopathy in sepsis is driven by an up-regulation of procoagulant mechanisms and simultaneous down-regulation of natural anticoagulants. Inflammation caused by the invading organism is a natural host defense than cannot be eliminated during treatment. Successful strategies to prevent MODS center on stratifying patients at high risk for DIC and restoring the balance of inflammation and coagulation. Summary The prevention of DIC in septic patients is a key therapeutic target in preventing death from multisystem organ failure. Stratifying patients for therapy using thromboelastometry, specific markers for DIC, and composite scoring systems is an area of growing research.

A Proposal of the Modification of Japanese Society on Thrombosis and Hemostasis (JSTH) Disseminated Intravascular Coagulation (DIC) Diagnostic Criteria for Sepsis-Associated DIC

“…21 Inflammation and coagulation have been widely accepted to play pivotal roles in the pathogenesis of sepsis, [22][23][24] and pro-thrombotic and antifibrinolytic reactions are both induced as part of the host defense scheme. [25][26][27] The other possible reason is the different reference value between the reagents. Since FDP was measured in the local laboratories, this might affect the result.…”

Microbial recognition and danger signals in sepsis and trauma

“…The near immediate release of cytokines and chemokines elicit an endothelial cell-target hypercoagulable state meant to reduce blood loss and trap microbial pathogens. Coagulopathy is likely driven by multiple pathways, and can be characterized by an early hypercoagulable state followed in some patients, especially those with adverse outcomes, by a consumptive coagulopathy and uncontrolled bleeding [47]. Under normal conditions of health, the vascular endothelium has a net anticoagulant state due to the constitutive expression of thrombomodulin, protein C and heparin [48].…”

How I treat disseminated intravascular coagulation

“…Initiation and propagation of procoagulant pathways with simultaneous impairment of natural anticoagulant systems and suppression of endogenous fibrinolysis as a result of systemic inflammatory activation are leading to platelet activation and fibrin deposition. 15,29 Important mediators that regulate these processes are cytokines, such as interleukin (IL)-1 and 6 and tumor necrosis factor (TNF)-. In addition, recent studies point to a prominent role of intravascular webs ('neutrophil-extracellular traps') consisting of denatured DNA from damaged cells and entangling neutrophils, plateles, fibrin and kationic proteins, such as histones, in the development of thrombus deposition.…”