Circulating microparticle levels are reduced in patients with ARDS

Abstract

BackgroundIt is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes.MethodsA total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times.ResultsARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50–0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49–0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time.ConclusionsElevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1700-7) contains supplementary material, which is available to authorized users.

Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study

“…Therefore, it appears obvious, that the presented cohort might be too small to draw any further conclusions regarding patient outcome. Interestingly, besides the mentioned studies suggesting a protective effect of MP due to effects on the coagulation system [ 9 – 11 ], a recent study could demonstrate reduced MP levels in patients with ARDS (Acute Respiratory Distress Syndrome) [ 26 ].…”

Investigation of the Opposite Capacities of Erythropoietin and U-74389G on Platelet Crit Levels

“…Htet et al [6] estimated almost 20% of critically ill patients having moderate-to-severe coagulopathy (platelets<50k/uL). Shaver et al [7] associated the elevated micro particle (MP) concentrations in the airspace during ARDS with activation of coagulation, reduced risk of ARDS and contribute to acute lung injury in critically ill patients. Etchill et al [8] associated the high platelets-to-packed RBCs ratio (>1:2) with decreased 48hour mortality 54.4% (p=0.032) in trauma patients.…”

Extracellular Vesicles in ARDS: New Insights into Pathogenesis with Novel Clinical Applications

“…In early ARDS, elevated BALF and plasma concentrations of leukocyte extracellular vesicles were associated with increased survival and ventilator-free days, thus suggesting a potential role for BALF and serum leukocyte extracellular vesicles as prognostic biomarkers in early ARDS. In a separate study, total plasma extracellular vesicle concentrations were measured in 280 critically ill patients on intensive care unit (ICU) admission; 90 of these patients subsequently developed ARDS [22]. Elevated plasma extracellular vesicle concentrations were associated with a lower risk of developing ARDS; this association was seen most strongly in patients admitted to ICU with sepsis.…”

“…Several studies that have investigated the role of extracellular vesicles in acute lung injury and ARDS have been done in animal and in vitro models, although one recent study was done in the ex vivo perfused human lung [12], and there are a few clinical studies as well [13,18,[21][22][23]. Future studies will need to characterize BALF and circulating extracellular vesicles from ARDS patients with regard to the cell of origin, cargo assessment (RNA, protein, organelle content), and their biological effect on human cells and human tissues.…”