Cargando…

Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries

BACKGROUND: Severe injury often results in substantial bleeding and mortality. Injury provokes cellular activation and release of extracellular vesicles. Circulating microvesicles (MVs) are predominantly platelet-derived and highly procoagulant. They support hemostasis and vascular function. The rol...

Descripción completa

Detalles Bibliográficos
Autores principales: Matijevic, Nena, Wang, Yao-Wei W., Holcomb, John B., Kozar, Rosemary, Cardenas, Jessica C., Wade, Charles E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Co-Action Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685295/
https://www.ncbi.nlm.nih.gov/pubmed/26689982
http://dx.doi.org/10.3402/jev.v4.29338
_version_ 1782406289436966912
author Matijevic, Nena
Wang, Yao-Wei W.
Holcomb, John B.
Kozar, Rosemary
Cardenas, Jessica C.
Wade, Charles E.
author_facet Matijevic, Nena
Wang, Yao-Wei W.
Holcomb, John B.
Kozar, Rosemary
Cardenas, Jessica C.
Wade, Charles E.
author_sort Matijevic, Nena
collection PubMed
description BACKGROUND: Severe injury often results in substantial bleeding and mortality. Injury provokes cellular activation and release of extracellular vesicles. Circulating microvesicles (MVs) are predominantly platelet-derived and highly procoagulant. They support hemostasis and vascular function. The roles of MVs in survival after severe injury are largely unknown. We hypothesized that altered MV phenotypes would be associated with transfusion requirements and poor outcomes. METHODS: This single-centre study was approved by the Institutional Review Board. The study cohort consisted of patients with major trauma requiring blood product transfusion and 26 healthy controls. Plasma samples for MVs were collected upon admission to the emergency department (n=169) and post-resuscitation (n=42), and analysed by flow cytometry for MV counts and cellular origin: platelet (PMV), erythrocyte (RMV), leukocyte (LMV), endothelial (EMV), tissue factor (TFMV), and annexin V (AVMV). Twenty-four hour mortality is the outcome measurement used to classify survivors versus non-survivors. Data were compared over time and analysed with demographic and clinical data. RESULTS: The median age was 34 (IQR 23, 51), 72% were male, Injury Severity Score was 29 (IQR 19, 36), and 24 h mortality was 13%. MV levels and phenotypes differed between patients and controls. Elevated admission EMVs were found both in survivors (409/µL) and non-survivors (393/µL) compared to controls (23/µL, p<0.001) and persisted over time. Admission levels of PMV, AVMV, RMV, and TFMV were significantly lower in patients who died compared to survivors, but were not independently associated with the 24 h mortality rate. Patients with low MV levels at admission received the most blood products within the first 24 h. AVMV and PMV levels either increased over time or stabilized in survivors but decreased in non-survivors, resulting in significantly lower levels at intensive care unit admission in non-survivors (1,048 vs. 1,880 AVMV/µL, p<0.00004 and 1,245 PMP/µL vs. 1,866 PMP/µL, p=0.003). CONCLUSION: Severe injury results in endothelial activation and altered MV phenotypes. Significant differences in specific MV phenotypes or changes over time were associated with blood product requirements and the 24 h mortality rate.
format Online
Article
Text
id pubmed-4685295
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Co-Action Publishing
record_format MEDLINE/PubMed
spelling pubmed-46852952016-01-06 Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries Matijevic, Nena Wang, Yao-Wei W. Holcomb, John B. Kozar, Rosemary Cardenas, Jessica C. Wade, Charles E. J Extracell Vesicles Original Research Article BACKGROUND: Severe injury often results in substantial bleeding and mortality. Injury provokes cellular activation and release of extracellular vesicles. Circulating microvesicles (MVs) are predominantly platelet-derived and highly procoagulant. They support hemostasis and vascular function. The roles of MVs in survival after severe injury are largely unknown. We hypothesized that altered MV phenotypes would be associated with transfusion requirements and poor outcomes. METHODS: This single-centre study was approved by the Institutional Review Board. The study cohort consisted of patients with major trauma requiring blood product transfusion and 26 healthy controls. Plasma samples for MVs were collected upon admission to the emergency department (n=169) and post-resuscitation (n=42), and analysed by flow cytometry for MV counts and cellular origin: platelet (PMV), erythrocyte (RMV), leukocyte (LMV), endothelial (EMV), tissue factor (TFMV), and annexin V (AVMV). Twenty-four hour mortality is the outcome measurement used to classify survivors versus non-survivors. Data were compared over time and analysed with demographic and clinical data. RESULTS: The median age was 34 (IQR 23, 51), 72% were male, Injury Severity Score was 29 (IQR 19, 36), and 24 h mortality was 13%. MV levels and phenotypes differed between patients and controls. Elevated admission EMVs were found both in survivors (409/µL) and non-survivors (393/µL) compared to controls (23/µL, p<0.001) and persisted over time. Admission levels of PMV, AVMV, RMV, and TFMV were significantly lower in patients who died compared to survivors, but were not independently associated with the 24 h mortality rate. Patients with low MV levels at admission received the most blood products within the first 24 h. AVMV and PMV levels either increased over time or stabilized in survivors but decreased in non-survivors, resulting in significantly lower levels at intensive care unit admission in non-survivors (1,048 vs. 1,880 AVMV/µL, p<0.00004 and 1,245 PMP/µL vs. 1,866 PMP/µL, p=0.003). CONCLUSION: Severe injury results in endothelial activation and altered MV phenotypes. Significant differences in specific MV phenotypes or changes over time were associated with blood product requirements and the 24 h mortality rate. Co-Action Publishing 2015-12-17 /pmc/articles/PMC4685295/ /pubmed/26689982 http://dx.doi.org/10.3402/jev.v4.29338 Text en © 2015 Nena Matijevic et al. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research Article
Matijevic, Nena
Wang, Yao-Wei W.
Holcomb, John B.
Kozar, Rosemary
Cardenas, Jessica C.
Wade, Charles E.
Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title_full Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title_fullStr Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title_full_unstemmed Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title_short Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
title_sort microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685295/
https://www.ncbi.nlm.nih.gov/pubmed/26689982
http://dx.doi.org/10.3402/jev.v4.29338
work_keys_str_mv AT matijevicnena microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries
AT wangyaoweiw microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries
AT holcombjohnb microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries
AT kozarrosemary microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries
AT cardenasjessicac microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries
AT wadecharlese microvesiclephenotypesareassociatedwithtransfusionrequirementsandmortalityinsubjectswithsevereinjuries