Fibrin turnover and pleural organization: bench to bedside

Abstract

Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including the mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, the mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.

Keywords: fibrinolysis; loculation; pleural disease.

Fig. 1.

Pleural organization from bench (A) to bedside (B and C). A: key events involved in the pathogenesis of pleural organization with formation of a fibrinous neomatrix, the increased presence of myofibroblasts and fibrotic remodeling within the pleural space. Arrows: facilitating interactions. Bars denote inhibition. Col 1, collagen 1; MesoMT, mesomesenchymal transition; PAI-1, plasminogen activator inhibitor-1; GSK-3β, glycogen synthase kinase-3β; KIF5A, kinesin 1 family member; PGN, plasminogen; PLN, plasmin generated by the cleavage of plasminogen buy plasminogen activators, here indicated by urokinase (uPA) or or tissue plasminogen activator (tPA), which are commonly used in clinical practice. B: pleural ultrasonography demonstrating loculation in a patient with pleural infection. Multiple adhesions have coalesced with septation of echogenic fluid into many locules that are seen throughout the imaged field. White arrows indicates the septations within the loculated pleural fluid. The cursor at the bottom right illustrates the plane of the imaged field. C; chest computed tomography imaging appearance of loculated pleural infection, which in this case illustrates extensive bilateral involvement. A representative coronal image that shows the loculated pleural process in this patient is shown here. The loculated pleural fluids are indicated within the right and left hemithoraces by black arrows.