High tPA activity but absent PAI-1 and plasminogen function early in intrapleural lytic therapy
Year: 2026
Type: article
Study design: Observational Study
Abstract: To the Editor Intrapleural fibrinolytic therapy (IPFT) for complicated parapneumonic effusions and empyema (CPE/E) is inefficient resulting in average hospital lengths of stay of 14 days and costs the U.S. healthcare system more than 1 billion dollars annually.1 The current dogma is that resistance to IPFT is related to elevated plasminogen activator inhibitor-1 (PAI-1), which inhibits tissue plasminogen activator (tPA).2-4 However, only 5–15% of PAI-1 in the pleural space is active, and the relatively high dose of tPA administered for standard IPFT should overcome active PAI-1 in a single dose given its 1:1 stoichiometric inhibitory capacity.3,5,6 Our study aimed to establish whether pleural fluid PAI-1 activity is suppressed by tPA administered during IPFT and to evaluate for free, active tPA (unbound to PAI-1) after IPFT. 26 adult inpatients with clinical diagnoses of CPE/E whose treating team had prescribed IPFT were included with Institutional Review Board approval (UNMC IRB #0101-24-FB, COMIRB #24–1369). One patient had bilateral empyema leading to inclusion of 27 CPE/E cases. Pleural fluid from the intrapleural catheter was collected into 3.2% sodium citrate anticoagulant, centrifuged, aliquoted, and stored at -80°C until assays. Samples were collected immediately before the patient’s first dose of IPFT (pre-IPFT), and within 1–180 minutes after unclamping of the catheter following completion of the one-hour dwell of their second (post-IPFTD1) and fourth dose (post-IPFTD2) of IPFT.
Authors: Elizabeth R Maginot, Peter K Moore, Cesar Davila-Chapa, Jiashan Wang, Henry Kramer, Christopher J King, Joseph J Mcbride, Reynold Henry, Daniel Hershberger, Christopher D Barrett, The PLUTO Study Group, Elizabeth R Maginot, Peter K Moore, Cesar Davila-Chapa, Jiashan Wang, Joseph Moran, Henry Kramer, Christopher King, Bryan Park, Trace B Moody, Grace E Volk, Kyle S Sextro, Dylan C Hiser, Ashley A Clegg, Flobater I Gawargi, Nicolle Barmettler, Ernest E Moore, Hunter B Moore, James G Chandler, Angela Sauaia, Olabisi O Sheppard, Collin M White, Keely Buesing, Michael B Yaffe, Benjamin T Haverkamp, Joseph J McBride, Zachary M Bauman, Reynold Henry, Daniel Hershberger, Christopher D Barrett
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7130874611