Disturbed alveolar fibrin turnover during pneumonia is associated with reduced activated protein C levels in lungs

Background

In pneumonia alveolar fibrin turnover is disturbed by activation of coagulation and inhibition of fibrinolysis. The role of natural coagulation inhibitors, such as activated protein C (APC), in lung inflammation is unknown.

Methods

In nine patients with unilateral pneumonia (four community-acquired [CAP], five ventilator associated [VAP]) bronchoalveolar lavage fluid (BALF) was obtained from both the infected and the contralateral noninfected lung. BALF levels of coagulation (thrombin–antithrombin complex [TATc]), fibrinolysis (plasminogen activator activity [PAA]), and levels of APC were determined. Ten healthy subjects and 10 mechanically ventilated patients without pneumonia served as controls.

Statistics

The Wilcoxon signed-ranked test was used for paired samples from the same patients; the Mann–Whitney U test was used for comparisons with controls.

Results

Higher levels of TATc and lower levels of PAA were found in infected lungs compared with noninfected lungs and lungs from controls (P < 0.05). Protein C and APC concentrations were significantly decreased at the infected site (P < 0.01). See Fig. 1.

Figure 1

Horizontal lines, median ± interquartile range from healthy (upper panels) and mechanically ventilated (lower panels) controls.

Conclusion

Pneumonia is characterized by a strong procoagulant shift at the site of infection, caused by local activation of coagulation, inhibition of fibrinolysis, and low levels of APC.