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Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern
Ivan E Rodriguez1,2, Jessica L Saben1,2, Ernest E Moore2,3
1Colorado Center for Transplantation Care, Research, and Education (CCTCARE), University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Insights
Fibrinolysis resistance, measured by tPA-TEG LY30, is a significant early indicator for pneumonia risk in ICU patients. A LY30 cutoff of less than 4% within 48 hours predicts increased pneumonia rates.
Area of Science:
- Critical Care Medicine
- Hemostasis and Thrombosis
- Infectious Diseases
Background:
- Pneumonia in the intensive care unit (ICU) leads to increased morbidity and costs.
- Early identification of pneumonia risk is crucial for patient outcomes, but reliable early biomarkers are lacking.
- Fibrinolysis resistance (FR) has been suggested as a potential risk factor for infection post-surgery.
Purpose of the Study:
- To evaluate fibrinolysis resistance (FR) as an early predictor of pneumonia in ICU patients.
- To determine the optimal cutoff for tPA-TEG LY30 indicative of increased pneumonia risk.
- To validate the association between FR and pneumonia in different ICU patient cohorts.
Main Methods:
- Patients from a hemorrhagic shock trial were assessed for FR using thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24 and 48 hours post-injury.
- The LY30 parameter was measured to quantify FR.
- Receiver-operating characteristic (ROC) curve analysis identified the optimal LY30 cutoff, which was then validated in ICU patients at risk for venous thromboembolism (VTE) and traumatic brain injury.
Main Results:
- A tPA-TEG LY30 of less than 4% at 24 and 48 hours was identified as the optimal cutoff for predicting increased pneumonia risk.
- In the hemorrhagic shock cohort, this cutoff was associated with a seven-fold increase in pneumonia rates.
- Validation cohorts (VTE and traumatic brain injury) showed similar associations, with the tPA-TEG LY30 cutoff predicting a 10-fold and 11-fold increase in pneumonia, respectively. The association remained significant after adjusting for confounders (aOR, 35.7).
Conclusions:
- Fibrinolysis resistance, quantified by tPA-TEG LY30 within 48 hours of ICU admission, is a significant risk factor for developing pneumonia.
- The identified tPA-TEG LY30 cutoff of <4% can aid in early pneumonia risk stratification for ICU patients.
- Further research is warranted to explore the causal link between endogenous FR and altered immunity in the context of pneumonia development.
Abstract:
Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.
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