Intrapleural fibrinolytic and enzyme therapy confers low overall bleeding risk in pleural infection: study

Pleural infection is a common and increasing clinical problem in thoracic medicine, resulting in significant morbidity and mortality. In recent years there has been a marked increase in interest and publications relating to evolving interventions and management options for pleural infection and empyema.

A combination of intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined.

This was a multicenter, retrospective observational study conducted in 24 centres across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination intrapleural fibrinolytic and enzyme therapy for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria.

Results of the study are:

• Overall, pleural bleeding occurred in 76 of 1,833 patients.
• Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly. Therapeutic anticoagulation alongside intrapleural fibrinolytic and enzyme therapy was associated with increased bleeding rates compared with temporarily withholding anticoagulation before administration of intrapleural fibrinolytic and enzyme therapy.
• As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk.
• However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, nonbleeding complications were rare.

Thus, intrapleural fibrinolytic and enzyme therapy use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation, but can be mitigated by withholding anticoagulation before intrapleural fibrinolytic and enzyme therapy. Concomitant administration of intrapleural fibrinolytic and enzyme therapy and therapeutic anticoagulation should be avoided. Parameters related to higher intrapleural fibrinolytic and enzyme therapy -related bleeding have been identified that may lead to altered risk thresholds for treatment.

Reference:

Jason Akulian, Eihab O. Bedawi, Hawazin Abbas, Najib M. Rahman, Lonny Yarmus. Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection

June 15, 2022 DOI: https://doi.org/10.1016/j.chest.2022.06.008