Quantification of TLT-1+ Microparticles to Predict Clinical Outcomes in ARDS - A Prognostic Marker

Document Type

Conference Proceeding

Publication Date

5-2025

Publication Title

American Journal of Respiratory and Critical Care Medicine

Abstract

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory condition with acute-onset hypoxemia with non-cardiogenic pulmonary edema, and bilateral opacities on lung radiograph. While the definition of ARDS has changed throughout the years, the Berlin Criteria specifies an arterial to inspired oxygen ratio (PaO2/FiO2) of < 300. ARDS is often complicated by thrombocytopenia and dysregulated hemostasis. This study aimed to investigate the association of triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+), glycoprotein (Gp) 1b, and αIIbβIIIa Microparticles (MPs) with clinical outcomes in ARDS. RATIONALE: Identify the association of triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+), glycoprotein (Gp) 1b, and αIIbβIIIa Microparticles (MPs) with clinical outcomes and disease severity in acute respiratory distress syndrome (ARDS). METHODS: We quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive MPs in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA ARDS Network clinical trials via flow cytometry. A total of 543 patients' blood samples were analyzed. Apache 3 scores were calculated for all patients and the number of days the patient survived up to 28 days. RESULTS: No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa + and TLT-1+ MPs (χ2 p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT1+ PMP in the 75th percentile. In all three cohorts, patients whose TLT1+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation (APACHE) III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors. The highest association with mortality was when high TLT1+ MP were divided by high platelet counts as shown in the Kaplan-Meir curve. CONCLUSIONS: Although both αIIbβIIIa + and TLT+ microparticles (αIIbβIIIa, TLT-1)were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with APACHE III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression especially when normalized for platelet count and its potential as a therapeutic target.

Volume

211

First Page

A1340

Last Page

A1340

Comments

American Thoracic Society (ATS) International Conference, May 16-21, 2025, San Francisco, CA

DOI

10.1164/ajrccm.2025.211.Abstracts.A1340

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