CHEST Guidelines-Plasminogen

Plasminogen_chest

Pdf Summary

Paul Y. Kim discusses the potential use of plasminogen in lytic therapy for pleural space infections. Infected pleural fluid often contains fibrin and neutrophils, leading to the formation of insoluble masses that hinder drainage. The standard treatment combines tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) I to break down these structures. However, about 20% of patients do not respond to this treatment. tPA primarily initiates fibrinolysis by converting plasminogen to plasmin, which then degrades fibrin. Nevertheless, some patients remain resistant due to potential deficiencies in plasminogen—plasma’s circulating fibrinolytic agent—leading to inadequate plasmin generation.<br /><br />Kim suggests that decreased plasminogen levels might underpin these treatment failures, with evidence pointing to nearly depleted plasminogen in nonrespondent patients. Elevated elastase in the pleural fluid, often released by neutrophils, may cleave plasminogen aside from inactivating plasminogen activator inhibitor 1 (PAI-1), further complicating therapy. This scenario implies that supplementation of plasminogen could restore fibrinolytic potential, making it a logical therapeutic approach when tPA/DNase I treatments fail.<br /><br />Currently, Ryplazim (Kedrion Biopharma), approved by the FDA for plasminogen deficiency treatment, might offer a novel strategy for promoting fibrinolysis in such cases. The author suggests additional studies into plasminogen supplementation, potentially including it in a mixture with tPA and DNase I for treating pleural infections. Testing for elastase activity or neutrophil activation biomarkers in patients might help identify those likely resistant to standard treatments. This approach could enhance treatment efficacy and control infection more effectively, although it requires more clinical exploration and validation.

Keywords

plasminogen

lytic therapy

pleural space infections

tissue plasminogen activator

deoxyribonuclease

fibrinolysis

treatment resistance

plasminogen supplementation

neutrophil activation

Ryplazim