Coagulation Dynamics in Severe Sepsis

Severe sepsis provokes a complex disturbance of haemostatic balance, in which dysregulated inflammation, endothelial injury and innate immune activation drive a shift towards excessive thrombin generation and microvascular thrombosis. This thromboinflammatory response, often termed immunothrombosis, aims to confine invading pathogens but can precipitate widespread microthrombi, organ ischaemia and disseminated intravascular coagulation (DIC). Underlying endothelial dysfunction, loss of anticoagulant surfaces and impaired fibrinolysis further exacerbate clot propagation. At the same time, consumptive coagulopathy depletes platelets and clotting factors, heightening the risk of bleeding. Recent advances have illuminated cell-specific pathways—such as neutrophil extracellular trap release, reactive oxygen species amplification of caspase-dependent coagulation cascades and alterations in the plasminogen–plasmin system—that reconcile the paradox of simultaneous thrombosis and haemorrhage. Improved understanding of these interwoven processes has spurred interest in targeted therapies that modulate upstream drivers of coagulopathy without compromising physiological haemostasis.

Research from Nature Portfolio

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Research from all publishers

Recent studies have elucidated reactive oxygen species–mediated mechanisms in sepsis-associated DIC and demonstrated that innovative antioxidant nanodots based on molybdenum compounds can inhibit caspase-11 activation, prevent phosphatidylserine exposure and block thrombin overproduction without provoking bleeding. Investigations into the plasminogen–plasmin axis have shown that restoring plasmin activity reduces neutrophil extracellular trap formation, diminishes systemic inflammation and fibrin deposition, improves efferocytosis and enhances survival when combined with antibiotics. Work on endothelial dysfunction and immunothrombosis has characterised how pathogen-activated monocytes and platelets trigger microvascular clotting, revealed the importance of glycocalyx preservation and identified novel targets for modulating platelet–endothelial interactions to mitigate organ injury and improve prognosis.

Coagulation Dynamics in Severe Sepsis publication trend

The graph below shows the total number of articles in coagulation dynamics in severe sepsis across all publications each year (not limited to Nature Index journals).

Technical terms

Disseminated intravascular coagulation (DIC): A pathological condition characterised by widespread activation of clotting with simultaneous depletion of platelets and coagulation factors, leading to both thrombosis and bleeding.

Neutrophil extracellular traps (NETs): Networks of DNA, histones and antimicrobial proteins released by activated neutrophils that can entrap pathogens but also promote clot formation.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can amplify inflammatory signalling and activate coagulation pathways.

Immunothrombosis: The host defence mechanism by which innate immune cells and coagulation factors collaborate to trap and neutralise pathogens within microvascular clots.

Plasminogen/plasmin system: The enzymatic cascade responsible for fibrin degradation and regulation of clot resolution and inflammation.

Endothelial dysfunction: Impairment of the vascular lining’s barrier and antithrombotic properties, leading to increased permeability, inflammation and procoagulant activity.

References

1. Anticoagulant therapy without bleeding: A novel molybdenum‐based nanodots alleviate lethal coagulation in bacterial sepsis by inhibiting ROS‐facilitated caspase‐11 activation. SmartMat (2024).
2. Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation. JCI Insight (2023).
3. Endothelial dysfunction and immunothrombosis in sepsis. Frontiers in Immunology (2023).