Fibrinolytic and inflammatory processes in pleural effusions

Abstract

F Fi ib br ri in no ol ly yt ti ic c a an nd d i in nf fl la am mm ma at to or ry y p pr ro oc ce es ss se es s i in n p pl le eu ur ra al l e ef ff fu us si io on ns s F. Philip-Joët*, M-C. Alessi**, C. Philip-Joët**, M. Aillaud**, J-R. Barriere*, A. Arnaud*, I. Juhan-Vague** Sixty patients with pleural effusion were studied. The underlying aetiology was empyema in 10 cases, tuberculosis in 9, cancer in 31, cardiac failure in 7, and undetermined in 3. Plasminogen, plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2), tissue type plasminogen activator (t-PA), urokinase (u-PA) and D-dimers (D-D) were quantified in plasma samples and pleural effusion specimens. These data were then correlated with inflammatory or infectious parameters, i.e. fibrinogen, von Willebrand factor (vWF), erythrocyte sedimentation rate (ESR), protein concentration, and white blood cell count.D-D levels were higher in pleural fluid than in plasma. D-D levels were not correlated with either plasminogen activator or plasminogen activator inhibitor levels, suggesting the presence of other fibrinolytic pathways. PAI levels (PAI activity, PAI-1 antigenicity, PAI-2 antigenicity) and vWF levels were significantly higher in patients with tuberculosis and empyema than in patients with cancer or cardiac failure. Regression analysis between inflammatory and fibrinolytic parameters showed that pleural PAI levels were significantly correlated with pleural neutrophil count, vWF levels, and plasma fibrinogen levels. D-D levels were correlated with blood ESR. No significant difference in pleural t-PA, u-PA and D-D levels was observed between aetiologies. The highest pleural t-PA and u-PA values were noted in patients with cancer, especially lymphoma. Plasma t-PA levels were higher in patients with pleural effusion secondary to congestive heart failure, but this difference did not reach statistical significance.In conclusion, pleural PAI levels are related to polymorphonuclear count and vWF levels, i.e. to inflammatory processes. Elevated levels of plasminogen activators suggest a possible role in some malignant pleural diseases.

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

“…The fibrinolytic system, which is responsible for fibrin balance, is regulated by a precise interplay between activators and inhibitors [20,21]. The plasminogen activators (PAs), tissue-type PA (t-PA) and urokinase PA (u-PA) modulate the activation of the inactive plasminogen precursor, which results in fibrin digestion and the production of soluble degradation products (D-dimer).…”

Decreased Proinflammatory Cytokines Production in Children with Complicated Parapneumonic Pleural Effusion after Intrapleural Fibrinolytic Treatment

“…In patients with CPE, high intrapleural levels of both t-PA, u-PA and their inhibitors (PAIs) have been found [7]. Intrapleural hypofibrinolysis, owing mainly to excessive concentration of inhibitors, has been postulated [1].…”

“…Though many reports have shown that pleural inflammatory response is mediated by the release of potent proinflammatory cytokines and fibrin deposition usually following pleural inflammation, the association between cytokines and the fibrinolytic system in pleural effusions is poorly understood [7,8,[21][22][23]. Intrapleural fibrinolytic therapy is a useful model to study the relationship of proinflammatory cytokines and fibrinolytic enzymes.…”

“…Proinflammatory cytokines may reduce fibrinolytic activity by stimulating the release of PAI-1 and result in an imbalance between PAI-1 and two PAs, tissue PA (t-PA) and urokinase PA (u-PA) in the pleural cavity. This imbalance leads to fibrin formation and deposition and subsequent loculation of the pleural effusion [2,3,[5][6][7][8]. These findings suggest a strong relationship between the fibrinolytic activity and proinflammatory cytokines in the pleural cavity.…”

Intrapleural r-tPA in Association with Low-Molecular Heparin May Cause Massive Hemothorax Resulting in Hypovolemia

“…The therapeutic action of r-tPA in the CPE is probably related to the pathogenesis of fibrin deposition in exudative pleural effusions, which includes an imbalance of coagulant and fibrinolytic activity secondary to a decreased level of endogenous r-tPA in the pleural fluid, and to the inhibition of plasminogen and plasmin by plasminogen activator inhibitors 1 and 2 and by other mediators [7,8]. r-tPA acts by breaking the fibrin loculations allowing easier drainage of the pleural fluid.…”