Coagulopathy in sepsis — a new look at an old problem

  Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis. According to a recently described new theory, immunothrombosis is a immune response in which the local activation of coagulation facilitates the recognition and destruction of pathogens. Small amounts of clot formation are beneficial for the host because of bacteria trapping and prevention of the systemic spread of infection. Sepsis is a dynamic syndrome and in all patients with sepsis coagulation changes may progress from a normal profile to hypercoagulability and hypofibrinolysis, hyperfibrinolysis, and ultimately hypocoagulability.    Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis. According to a recently described new theory, immunothrombosis is a immune response in which the local activation of coagulation facilitates the recognition and destruction of pathogens. Small amounts of clot formation are beneficial for the host because of bacteria trapping and prevention of the systemic spread of infection. Sepsis is a dynamic syndrome and in all patients with sepsis coagulation changes may progress from a normal profile to hypercoagulability and hypofibrinolysis, hyperfibrinolysis, and ultimately hypocoagulability.

Neutrophils, NETs, NETosis — old or new factors in sepsis and septic shock?

  Neutrophils are an key part of the innate immune system in the host’s defences against pathogens. Circulating neutrophils are recruited at the sites of infection or sterile inflammation in response to pathogen and host-derived inflammatory mediators. In addition to phagocytosis and degranulation, neutrophils display the release of NETs in order to restrain infection. NETs are able to entrap and kill microbes, and display proinflammatory and prothrombotic properties.    Neutrophils are an key part of the innate immune system in the host’s defences against pathogens. Circulatingneutrophils are recruited at the sites of infection or sterile inflammation in response to pathogen and host-derivedinflammatory mediators. In addition to phagocytosis and degranulation, neutrophils display the release of NETs inorder to restrain infection. NETs are able to entrap and kill microbes, and display proinflammatory and prothromboticproperties

Platelets in sepsis — are there any new aspects?

  Platelets display a number of properties besides the crucial function of repairing a damaged vascular endothelium and stopping bleeding. Platelets constitutively express molecules that are classically acknowledged to function in primary haemostasis. Platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Recently, platelets expressing receptors for infectious and possibly noninfectious danger signals were shown to be involved in pathophysiological reactions including an immune-inflammatory response. In sepsis, platelets play a key role in immunothrombosis, participate in the formation of NETs (neutrophil extracellular trap) resulting in the trapping and killing of pathogens and are one of the main factors influencing mortality.    Platelets display a number of properties besides the crucial function of repairing a damaged vascular endothelium and stopping bleeding. Platelets constitutively express molecules that are classically acknowledged to function in primary haemostasis. Platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Recently, platelets expressing receptors for infectious and possibly noninfectious danger signals were shown to be involved in pathophysiological reactions including an immune-inflammatory response. In sepsis, platelets play a key role in immunothrombosis, participate in the formation of NETs (neutrophil extracellular trap) resulting in the trapping and killing of pathogens and are one of the main factors influencing mortality

Sepsis and septic shock – is a microcirculation a main player?

Shock, defined at a cellular level, is a condition in which oxygen delivery to the cells is not sufficient to sustain cellular activity and support organ function. The central role of microcirculation in providing oxygen to the cells makes it of prime importance in determining organ function. In sepsis and septic shock, macrocirculatory alterations and microcirculatory dysfunction participate concurrently in the pathophysiology of organ failure. Haemodynamic coherence in shock is a condition in which normalization of systemic haemodynamic variables results in simultaneous amelioration in the perfusion of the microcirculation and restoration of tissue oxygenation as a final result. Septic shock is most frequently characterized by a lack of microcirculatory recruitment despite of macrocirculatory successful resuscitation. The lack of haemodynamic coherence between macrocirculation and microcirculation in septic patients results in treatment failure and increased mortality. The monitoring of microcirculation and the effects of its changes are an important area of future clinical research and treatment modification.Shock, defined at a cellular level, is a condition in which oxygen delivery to the cells is not sufficient to sustain cellular activity and support organ function. The central role of microcirculation in providing oxygen to the cells makes it of prime importance in determining organ function. In sepsis and septic shock, macrocirculatory alterations and microcirculatory dysfunction participate concurrently in the pathophysiology of organ failure. Haemodynamic coherence in shock is a condition in which normalization of systemic haemodynamic variables results in simultaneous amelioration in the perfusion of the microcirculation and restoration of tissue oxygenation as a final result. Septic shock is most frequently characterized by a lack of microcirculatory recruitment despite of macrocirculatory successful resuscitation. The lack of haemodynamic coherence between macrocirculation and microcirculation in septic patients results in treatment failure and increased mortality. The monitoring of microcirculation and the effects of its changes are an important area of future clinical research and treatment modification