Coagulation and fibrinolysis in human acute lung injury--new therapeutic targets?
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS. This review summarizes our current understanding of coagulation and fibrinolysis in human ALI/ARDS with an emphasis on pathways that could be potential therapeutic targets including the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1. The available data suggest that clinical ALI and ARDS are characterized by profound alterations in both systemic and intra-alveolar coagulation and fibrinolysis. Fibrin deposition in the airspaces and lung microvasculature likely results from both activation of the coagulation cascade and impaired fibrinolysis, triggered by inflammation. Modulation of fibrin deposition in the lung through targeting activation and modulation of coagulation as well as fibrinolysis may be an important therapeutic target in clinical ALI/ARDS that deserves further exploration.
Associated Clinical Trials
Procoagulant activity in bronchoalveolar fluids: no relationship with tissue factor pathway inhibitor activity
Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome
Phosphorylation of a pancreatic zymogen granule membrane protein by endogenous calcium/phospholipid-dependent protein kinase
Degradation of fibrin and elastin by intact human alveolar macrophages in vitro. Characterization of a plasminogen activator and its role in matrix degradation
Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis
Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis
Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome
The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex
Subthreshold hyperoxia potentiates TNF-alpha-induced ICAM-1 expression on cultured pulmonary microvascular endothelial cells
Increased secretion of urokinase-type plasminogen activator by human lung microvascular endothelial cells
4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group
Systemic activation of tissue-factor dependent coagulation pathway in evolving acute respiratory distress syndrome in patients with trauma and sepsis
Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome
Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis
Recombinant tissue factor pathway inhibitor reduces lipopolysaccharide-induced pulmonary vascular injury by inhibiting leukocyte activation
Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients
Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study
Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide
Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial
Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury
Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial
The clinical evaluation committee in a large multicenter phase 3 trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): role, methodology, and results
Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study
Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism in susceptibility, severity, and outcome of meningococcal disease in Caucasian children
Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: role of bacterial pathogens
Alveolar hemostasis in patients with species-specific bacterial-mediated ventilator-associated pneumonia
Early intravenous unfractionated heparin and outcome in acute lung injury and acute respiratory distress syndrome: a retrospective propensity matched cohort study
Lactobacillus casei modulates the inflammation-coagulation interaction in a pneumococcal pneumonia experimental model
Low anticoagulant heparin blocks thrombin-induced endothelial permeability in a PAR-dependent manner
Effects of direct hemoperfusion with polymyxin B-immobilized fiber on rapidly progressive interstitial lung diseases
Mechanical stretch inhibits lipopolysaccharide-induced keratinocyte-derived chemokine and tissue factor expression while increasing procoagulant activity in murine lung epithelial cells.
Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice
Suppression of plasminogen activator inhibitor-1 by inhaled nitric oxide attenuates the adverse effects of hyperoxia in a rat model of acute lung injury
Emerging role of anticoagulants and fibrinolytics in the treatment of acute respiratory distress syndrome
Thrombin activatable fibrinolysis inhibitor activity, thrombin-antithrombin complex and D-dimer levels in preterm neonates with early respiratory distress syndrome
Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through anti-inflammation
Role of pneumococcal pneumolysin in the induction of an inflammatory response in human epithelial cells
MKP1 regulates the induction of inflammatory response by pneumococcal pneumolysin in human epithelial cells
Proteomic profiles in acute respiratory distress syndrome differentiates survivors from non-survivors
Efficacy of recombinant human soluble thrombomodulin for the treatment of acute exacerbation of idiopathic pulmonary fibrosis: a single arm, non-randomized prospective clinical trial
Direct hemoperfusion using immobilized polymyxin B in patients with rapidly progressive interstitial pneumonias: a retrospective study
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