Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern

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.