Bleeding risk with combination intrapleural fibrinolytic and enzyme therapy in pleural infection - an international, multicenter, retrospective cohort study.

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bleeding; empyema; fibrinolysis; intrapleural; parapneumonic pleural effusion; washington; swedish; swedish thoracic


BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, there is a sparsity of studies specifically designed and adequately powered to address complications. The safety profile, the effects of concurrent therapeutic anticoagulation and the nature/extent of non-bleeding complications remain poorly defined.

RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection?

STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection on 1851 patients treated with at least one dose of combination IET 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: Overall pleural bleeding incidence was 76/1833=4.1% (95%CI 3.0% to 5.0%). Using a half-dose regimen (tPA 5mg) did not significantly change this risk (6/172=3.5%; p=0.68). Therapeutic anticoagulation (AC) alongside IET was associated with increased bleeding rates (19/197=9.6%) compared to temporarily withholding AC prior to administration of IET (3/118=2.6%, p=0.017). As well as systemic AC, increasing RAPID score, an elevated serum urea and platelets <100x10

INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of AC but can be mitigated by withholding AC prior to IET. Concomitant administration of IET and therapeutic AC should be avoided. Parameters related to higher IET related bleeding have been identified which may lead to altered risk thresholds for treatment.


Pulmonary Medicine