Coagulopathy in Critical Illness

Coagulopathy in critical illness is the disturbance of haemostasis that accompanies severe inflammatory states such as sepsis and major trauma. Inflammation and coagulation are tightly coupled, so a dysregulated host response can simultaneously promote microvascular thrombosis and, through consumption of clotting factors and platelets, a bleeding tendency — culminating in some patients in disseminated intravascular coagulation.

Definition

Coagulopathy in critical illness denotes acquired derangement of the haemostatic system driven by systemic inflammation and endothelial injury, characterised by activation of coagulation, impaired anticoagulant and fibrinolytic pathways, and consumption of platelets and clotting factors, spanning from compensated activation to overt disseminated intravascular coagulation.

Scope

This entry describes the bidirectional crosstalk between inflammation and coagulation, the concept of immunothrombosis, and the spectrum from sepsis-induced coagulopathy to disseminated intravascular coagulation. It is pathophysiological reference material and does not give anticoagulation, transfusion, or other treatment guidance for individual patients.

Core questions

• How are inflammation and coagulation mechanistically linked during critical illness?
• What is immunothrombosis and how does it become harmful?
• How does the same process produce both microvascular thrombosis and bleeding?
• What distinguishes compensated coagulopathy from disseminated intravascular coagulation?

Key concepts

• Inflammation-coagulation crosstalk
• Immunothrombosis
• Tissue-factor-driven activation
• Impaired anticoagulant pathways
• Suppressed fibrinolysis
• Consumption of platelets and clotting factors
• Disseminated intravascular coagulation (DIC)

Mechanisms

Systemic inflammation and endothelial injury expose and induce tissue factor, activating the coagulation cascade, while natural anticoagulant systems and fibrinolysis are simultaneously impaired. Thrombin generation and platelet activation promote intravascular fibrin deposition. As an evolutionarily conserved arm of innate immunity, this immunothrombosis can help contain pathogens, but when dysregulated it produces widespread microvascular thrombosis that contributes to organ dysfunction. Ongoing activation consumes platelets and clotting factors, so the same disorder that causes thrombosis can also produce a consumptive bleeding tendency; the severe, decompensated end of this spectrum is disseminated intravascular coagulation (Levi & Ten Cate, 2007; Engelmann & Massberg, 2013; Gando et al., 2016).

Clinical relevance

Coagulopathy links the systemic inflammatory and endothelial responses of critical illness to microvascular thrombosis and organ dysfunction, and it is part of why severe sepsis and trauma carry high mortality. This entry explains the underlying biology and the concept of disseminated intravascular coagulation for orientation; it is descriptive and does not provide anticoagulant dosing, transfusion thresholds, or individualised management advice.

History

The understanding of haemostatic disturbance in critical illness evolved from describing disseminated intravascular coagulation as a consumptive syndrome toward an integrated view of inflammation and coagulation as a coupled system. Reviews by Levi and colleagues established the clinical concept of disseminated intravascular coagulation, and the framing of thrombosis as an effector of innate immunity by Engelmann and Massberg in 2013 introduced immunothrombosis, reframing coagulopathy as part of the host defence response that becomes injurious when dysregulated.

Debates

Should the coagulopathy of critical illness be modified pharmacologically?

Because activated coagulation contributes to organ dysfunction, strategies to modulate it have been explored, but evidence for anticoagulant or pro-haemostatic interventions in sepsis-associated coagulopathy is mixed and contested; thromboprophylaxis in critically ill patients has a stronger evidence base for preventing venous thromboembolism than do disease-modifying anticoagulant strategies for coagulopathy itself.

Key figures

• Marcel Levi
• Bernd Engelmann
• Steffen Massberg
• Satoshi Gando

Seminal works

• levi-2007
• engelmann-2013
• gando-2016

Frequently asked questions

What is immunothrombosis?

Immunothrombosis is the concept that clot formation is part of the innate immune response, helping to contain pathogens within blood vessels; when this process is dysregulated in critical illness it contributes to harmful microvascular thrombosis and organ dysfunction.

Why can critically ill patients both clot and bleed?

Dysregulated coagulation drives intravascular thrombosis while consuming platelets and clotting factors and impairing their replacement, so the same disorder can produce microvascular clotting and, simultaneously, a tendency to bleed — most strikingly in disseminated intravascular coagulation.