Increased plasma fibrinolytic activity in bleeding gastrointestinal angiodysplasia.

OBJECTIVE: Gastrointestinal angiodysplasia is a major cause of recurrent bleeding. Haemostatic abnormalities have been implicated in the haemorrhage from these common vascular lesions but their precise contribution remains to be established. Our aim was to investigate whether bleeding angiodysplasia is associated with any specific coagulation disorder. METHODS: Clinical features and blood samples were prospectively obtained from 21 patients with bleeding gastrointestinal angiodysplasia 3 months after the last episode of haemorrhage. Plasma levels of von Willebrand factor, D-dimer, plasminogen activator inhibitor type 1 (PAI-1), tissue-plasminogen activator activity, tissue factor pathway inhibitor and activated factor VII (FVIIa-rTF) were measured. A group of 14 patients with bleeding duodenal ulcer were similarly studied as controls. RESULTS: Mean plasma von Willebrand factor levels were higher in angiodysplasia patients (208+/-12%) than in controls (143+/-11%) (P<0.05). D-dimer levels (661+/-80 ng/ml) and tissue-plasminogen activator activity levels (2.04+/-0.14 IU/ml) were also higher than in controls: 395+/-99 ng/ml and 1.6+/-0.1 IU/ml, respectively (P<0.05), whereas levels of PAI-1, FVIIa-rTF and tissue factor pathway inhibitor were similar in both groups. However, PAI-1 levels (31.5+/-11 ng/ml) were lower in high-bleeding-rate angiodysplasia (more than two bleeding episodes/year) than in low-bleeding-rate angiodysplasia (< or = 2 bleeding episodes/year) (PAI-1 47+/-14 ng/ml) (P<0.05). In a multivariate regression analysis, the plasma level of PAI-1 was a predictor of haemorrhage from angiodysplasia (P<0.05). CONCLUSIONS: Increased plasma fibrinolytic activity may contribute to bleeding from angiodysplasia. Low plasma PAI-1 levels constitute a risk factor for bleeding tendency in patients with angiodysplasia.

Association between inflammatory mediators and the fibrinolysis system in infectious pleural effusions.

The response of the fibrinolytic system to inflammatory mediators in empyema and complicated parapneumonic pleural effusions is still uncertain. We prospectively analysed 100 patients with pleural effusion: 25 with empyema or complicated parapneumonic effusion, 22 with tuberculous effusion, 28 with malignant effusion and 25 with transudate effusion. Inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and polymorphonuclear elastase, were measured in serum and pleural fluid. Fibrinolytic system parameters, plasminogen, tissue-type plasminogen activator (t-PA) and urokinase PA, PA inhibitor type 1 (PAI 1) and PAI type 2 concentrations and PAI 1 activity, were quantified in plasma and pleural fluid. The Wilcoxon signed-rank test was used to compare plasma and pleural values and to compare pleural values according to the aetiology of the effusion. The Pearson correlation coefficient was used to assess the relationship between fibrinolytic and inflammatory markers in pleural fluid. Significant differences were found between pleural and plasma fibrinolytic system levels. Pleural fluid exudates had higher fibrinolytic levels than transudates. Among exudates, tuberculous, empyema and complicated parapneumonic effusions demonstrated higher pleural PAI levels than malignant effusions, whereas t-PA was lowest in empyema and complicated parapneumonic pleural effusions. PAI concentrations correlated with TNF-alpha, IL-8 and polymorphonuclear elastase when all exudative effusions were analysed, but the association was not maintained in empyema and complicated parapneumonic effusions. A negative association found between t-PA and both IL-8 and polymorphonuclear elastase in exudative effusions was strongest in empyema and complicated parapneumonic effusions. Blockage of fibrin clearance in empyema and complicated parapneumonic effusions was associated with both enhanced levels of PAIs and decreased levels of t-PA.