Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia.
Schultz MJ., Millo J., Levi M., Hack CE., Weverling GJ., Garrard CS., van der Poll T.
BACKGROUND: Fibrin deposition is a hallmark of pneumonia. To determine the kinetics of alterations in local coagulation and fibrinolysis in relation to ventilator associated pneumonia (VAP), a single centre prospective study of serial changes in pulmonary and systemic thrombin generation and fibrinolytic activity was conducted in patients at risk for VAP. METHODS: Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP. RESULTS: In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1. CONCLUSION: VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.