Coagulation and Inflammation in Pulmonary Pathophysiology

The lung maintains a delicate balance between coagulation and inflammation to preserve gas exchange and vascular integrity. In response to infection or injury, endothelial cells, platelets and innate immune cells interact via cytokines, adhesion molecules and protease cascades. Excessive activation of coagulation leads to fibrin deposition in alveolar spaces and microvessels, while unresolved inflammation perpetuates tissue damage and oedema. This bidirectional crosstalk—often termed thrombo-inflammation—underlies conditions such as acute respiratory distress syndrome, severe pneumonia and sepsis-associated lung injury. Understanding the molecular mediators and cell-specific mechanisms is critical for developing therapies that restore homeostasis without compromising host defence.

Research from Nature Portfolio

Recent studies have shown that distinct inflammatory signals drive thrombosis with organ-specific features in systemic infection models. In experimental Salmonella Typhimurium infection, spleen and liver thrombi form through overlapping but non-identical pathways: monocytes and neutrophils release tumour necrosis factor to upregulate endothelial adhesion molecules, while tissue factor and P-selectin ligand pathways amplify clot formation. Selective blockade of these axes reduces thrombosis and inflammation in each organ. These findings highlight the benefit of targeting both coagulation initiators and inflammatory mediators in an organ-tailored manner.

Coagulation and Inflammation in Pulmonary Pathophysiology publication trend

The graph below shows the total number of articles in coagulation and inflammation in pulmonary pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Coagulation: cascade of protease activations culminating in fibrin clot formation to prevent bleeding.

Inflammation: coordinated immune response involving cytokine release, leukocyte recruitment and vascular changes.

Thrombo-inflammation: intertwined activation of clotting and immune pathways leading to microvascular obstruction.

Acute respiratory distress syndrome (ARDS): severe form of lung injury marked by diffuse alveolar damage, oedema and hypoxaemia.

Tissue factor: membrane receptor that initiates the extrinsic coagulation pathway and modulates inflammatory signalling.

Plasminogen activator inhibitor-1 (PAI-1): major inhibitor of fibrinolysis that promotes fibrin persistence.

RUNX1: transcription factor regulating genes involved in both coagulation and inflammatory responses.

Nuclear factor κB (NF-κB): transcriptional regulator of a wide range of pro-inflammatory and pro-coagulant genes.

References

1. Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection. Nature Communications (2025).
2. RUNX1 targeting AKT3 promotes alveolar hypercoagulation and fibrinolytic inhibition in LPS induced ARDS. Respiratory Research (2024).
3. 6-Gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition in LPS-provoked ARDS via RUNX1/NF-κB signaling pathway. International Immunopharmacology (2024).