Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome.

Intraalveolar fibrin deposition is a typical finding in acute lung injury and is not necessarily harmful. However, persistence of intraalveolar fibrin deposit may lead to hyaline membrane formation and subsequent alveolar fibrosis, a histologic hallmark of late stages of acute respiratory distress syndrome (ARDS). Thus, timing of the intraalveolar clotting disorder seems to be critical. To explore the time course of factors contributing to fibrin deposition and resolution, we sequentially analyzed procoagulant activity and fibrin degradation (by D dimer) in bronchoalveolar lavage (BAL) fluid of patients developing ARDS and those at risk for, but finally not developing, the syndrome. A total of 36 bronchoalveolar lavages were performed in 11 patients developing ARDS and 15 lavages in 10 patients at risk for but not developing this syndrome. All patients were admitted to the intensive care unit for the treatment of sepsis, trauma, or shock. In early phases of ARDS, the procoagulant activity (PCA) in BAL was significantly higher than in the patients at risk, 320 +/- 83 U (mean +/- SEM) versus 50 +/- 25 U, p < 0.05. A similar difference was noted in subacute stages (280 +/- 91 versus 46 +/- 16 U, p < 0.05). In early ARDS we observed higher levels of D dimer in BAL than in patients at risk: 1,841 +/- 827 versus 293 +/- 134 ng/ml, p < 0.05. Similarly, values of D dimer in the subacute phase were 2,776 +/- 836 versus 237 +/- 125 ng/ml, p < 0.05. In ARDS as well as in the at-risk group, D dimer in BAL fluid showed good correlation with the polymorphonuclear leukocyte count and with protein content of BAL. There was no correlation between plasma and BAL levels of D dimer. We conclude that in ARDS both the procoagulant pathway and the fibrin degradation are markedly activated compared with these in patients at risk but finally not developing this syndrome. These findings expand our understanding of intraalveolar coagulation abnormalities by providing evidence of increased fibrin breakdown in this syndrome.

Procoagulant and fibrinolytic activities in bronchoalveolar fluid of HIV-positive and HIV-negative patients.

Imbalance between intra-alveolar procoagulant activity (PCA) and fibrinolytic activity may lead to fibrin deposition, as described in several pneumopathies, and may eventually contribute to fibrotic changes as observed in Pneumocystis carinii pneumonia (PCP). The aim of our study was to compare these activities in bronchoalveolar lavages of human immunodeficiency virus (HIV)-positive and HIV-negative patients. The material comprised: a) controls (n = 7); b) HIV-positive patients subdivided into PCP (n = 11), bacterial pneumonia (n = 8) and other pneumopathies (n = 22); and c) HIV-negative patients with bacterial pneumonia (n = 8). PCA was significantly increased (p less than 0.05) in all patient groups compared to controls. The urokinase-type plasminogen activator (u-PA) antigen levels were highest during bacterial pneumonia. Regardless of the HIV status, in bacterial pneumonia there was a marked elevation of plasminogen activator inhibitor antigens with little residual fibrinolytic activity. In contrast, the fibrinolytic activity was not decreased in PCP. D-dimer were elevated during PCP compared to controls; the highest levels were found in HIV-negative bacterial pneumonia. These data indicate that transient fibrotic changes seen in PCP may be favoured by increased PCA, but not by a depressed fibrinolytic activity. In bacterial pneumonia PCA is increased and fibrinolysis decreased independently of the HIV status.

Procoagulant activity in bronchoalveolar fluids: no relationship with tissue factor pathway inhibitor activity.

Abnormalities in local coagulation may explain alveolar fibrin deposition which often accompanies human lung injuries. The purpose of this study was to investigate the generation of procoagulant activity (PCA) and tissue factor pathway inhibitor (TFPI) in selected bronchoalveolar lavage fluids (BAL) from controls (n = 7) and from patients with interstitial lung diseases (n = 9), Pneumocystis carinii (PCP) pneumonia (n = 11) and bacterial pneumonia (n = 8). As compared with controls a significant increase of PCA was observed in the three groups with lung diseases. PCA in BAL from patients with untreated interstitial lung diseases (PC Units mean of 162 +/- 48) was significantly higher than PCA of treated patients (PC Units 36 +/- 10; p less than 0.05). Increases of PCA paralleled protein levels in BAL and the protein/albumin ratios were comparable in the four groups. TFPI was significantly increased in PCP (p less than 0.02) and bacterial pneumonia (p less than 0.03), but only marginally increased in interstitial lung diseases when compared with controls. No correlation was found between TFPI and PCA in any of the four groups. These data indicate that increased procoagulant activity observed in various lung diseases is not counterbalanced by TFPI.