PB0770 - High levels of TLT-1+, but not Gp1b+, Microparticles Are Indicative of Poor Outcomes in Acute Respiratory Distress Syndrome

Background: Microparticles (MPs) are cellular fragments that range in size from 50 to 1000 nm. MPs have been shown to mediate cellular communication, as well as thrombosis, in disease states. In the vasculature, MPs are derived from each of the cellular components (platelets, granulocytes, endothelial cells, monocytes, and red blood cells). Several studies have evaluated the prominence of MPs during Acute Respiratory Distress Syndrome (ARDS) and have identified correlations with disease severity and the presence of alveolar endothelial cell MPs, particularly those that contain the coagulation initiator, tissue factor (TF). Oddly, no associations have been reported with platelet-derived MPs, even though platelets are predicted to produce an estimated 80% of circulating MPs. Recently, our group has found that increased levels of the soluble TREM – like transcript -1 (TLT-1) is associated with increased mortality and decreased ability to obtain unassisted breathing and is thus a prognostic indicator for ARDS. Full-length TLT-1 binds fibrinogen and is a platelet-specific receptor that is stored in platelet granules and brought to the surface upon platelet activation.

Aims: In this study we hypothesized the existence of TLT-1 positive microparticles and that their presence would correlate with disease severity in ARDS.

Methods: We retrospectively quantified TLT-1, Gp1b, a2bb3, or P-selectin positive microparticles using flow cytometry in plasma samples from the ARDS Network clinical trials and correlated the data with clinical outcomes.

Results: No correlations were found with Gp1b+ or P-selectin+ MPs. When divided into quartiles, correlations were found with coagulation failure and survival with a2bb3+ and TLT-1 + MPs (chi sq p< 0.001). Only TLT-1+ MPs correlated with MSOF (multi-system organ failure), APACHE II scores and unassisted breathing (p < 0.001).

Conclusion(s): While both fibrinogen binding+ microparticles (2b3, TLT-1) correlated with survival, TLT-1+ MPs demonstrated stronger correlations with APACHE II scores, unassisted breathing, and MSOF.