Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis

Abstract Background Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis...

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Main Authors: Georg Franz Lehner, Ulrich Harler, Clemens Feistritzer, Viktoria Maria Haller, Julia Hasslacher, Romuald Bellmann, Michael Joannidis
Format: Article
Language:English
Published: SpringerOpen 2017-09-01
Series:Annals of Intensive Care
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13613-017-0312-3
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author Georg Franz Lehner
Ulrich Harler
Clemens Feistritzer
Viktoria Maria Haller
Julia Hasslacher
Romuald Bellmann
Michael Joannidis
author_facet Georg Franz Lehner
Ulrich Harler
Clemens Feistritzer
Viktoria Maria Haller
Julia Hasslacher
Romuald Bellmann
Michael Joannidis
author_sort Georg Franz Lehner
collection DOAJ
description Abstract Background Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis. On the other hand, proinflammatory stimuli are induced by blood contacting the artificial membrane during extracorporeal blood purification. In chronic dialysis patients a systemic increase in MV has been described. The aim of the study was to investigate whether hemofilter passage of blood in continuous veno-venous hemofiltration (CVVH) alters MV composition and levels in critically ill patients with sepsis. Methods Pre- and postfilter bloods as well as ultrafiltrate samples from intensive care unit patients with severe sepsis were obtained during CVVH with regional citrate anticoagulation. MV subtypes in blood were analyzed by high-sensitivity flow cytometry. Additionally, tissue factor (TF) levels and MV-associated TF activities as well as MV activities were quantified. All parameters were corrected for hemoconcentration applied during CVVH. Results Twelve patients were analyzed. A significant increase in presumably mostly leukocyte-derived CD31+/CD41− MV (1.32 (1.09–1.93)-fold [median (25th–75th quartiles)], p = 0.021) was observed post- to prefilter, whereas platelet-derived MV as well as AnnexinV-binding MV were unaltered. Increments of AnnexinV+, CD42b+ and CD31+/CD41− MV post- to prefilter correlated with filtration fraction (FF) (all p < 0.05). Significant reductions in MV activity [0.72 (0.62–0.84)-fold, p = 0.002] and TF level [0.95 (0.87–0.99)-fold, p = 0.0093] were detected postfilter compared to prefilter. No MV activity was measurable in ultrafiltrate samples. Conclusions Despite clearing a fraction of small PS-exposing MV CVVH does not eliminate larger MV. Concurrently, CVVH induces the release of CD31+/CD4− MV that indicate leukocyte activation during hemofilter passage in septic patients. Increments of several MV subtypes within the hemofilter correlate with FF, which supports common recommendations to keep FF low. A fraction of TF is being cleared by CVVH via ultrafiltration.
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spelling doaj.art-56c7e40d336e4979a509d058a1753c552022-12-22T03:10:30ZengSpringerOpenAnnals of Intensive Care2110-58202017-09-01711810.1186/s13613-017-0312-3Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsisGeorg Franz Lehner0Ulrich Harler1Clemens Feistritzer2Viktoria Maria Haller3Julia Hasslacher4Romuald Bellmann5Michael Joannidis6Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckDepartment of Internal Medicine V - Haematology and Oncology, Medical University InnsbruckDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University InnsbruckAbstract Background Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis. On the other hand, proinflammatory stimuli are induced by blood contacting the artificial membrane during extracorporeal blood purification. In chronic dialysis patients a systemic increase in MV has been described. The aim of the study was to investigate whether hemofilter passage of blood in continuous veno-venous hemofiltration (CVVH) alters MV composition and levels in critically ill patients with sepsis. Methods Pre- and postfilter bloods as well as ultrafiltrate samples from intensive care unit patients with severe sepsis were obtained during CVVH with regional citrate anticoagulation. MV subtypes in blood were analyzed by high-sensitivity flow cytometry. Additionally, tissue factor (TF) levels and MV-associated TF activities as well as MV activities were quantified. All parameters were corrected for hemoconcentration applied during CVVH. Results Twelve patients were analyzed. A significant increase in presumably mostly leukocyte-derived CD31+/CD41− MV (1.32 (1.09–1.93)-fold [median (25th–75th quartiles)], p = 0.021) was observed post- to prefilter, whereas platelet-derived MV as well as AnnexinV-binding MV were unaltered. Increments of AnnexinV+, CD42b+ and CD31+/CD41− MV post- to prefilter correlated with filtration fraction (FF) (all p < 0.05). Significant reductions in MV activity [0.72 (0.62–0.84)-fold, p = 0.002] and TF level [0.95 (0.87–0.99)-fold, p = 0.0093] were detected postfilter compared to prefilter. No MV activity was measurable in ultrafiltrate samples. Conclusions Despite clearing a fraction of small PS-exposing MV CVVH does not eliminate larger MV. Concurrently, CVVH induces the release of CD31+/CD4− MV that indicate leukocyte activation during hemofilter passage in septic patients. Increments of several MV subtypes within the hemofilter correlate with FF, which supports common recommendations to keep FF low. A fraction of TF is being cleared by CVVH via ultrafiltration.http://link.springer.com/article/10.1186/s13613-017-0312-3SepsisMicrovesiclesMicroparticlesHemofiltrationContinuous veno-venous hemofiltrationRenal replacement therapy
spellingShingle Georg Franz Lehner
Ulrich Harler
Clemens Feistritzer
Viktoria Maria Haller
Julia Hasslacher
Romuald Bellmann
Michael Joannidis
Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
Annals of Intensive Care
Sepsis
Microvesicles
Microparticles
Hemofiltration
Continuous veno-venous hemofiltration
Renal replacement therapy
title Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
title_full Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
title_fullStr Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
title_full_unstemmed Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
title_short Hemofiltration induces generation of leukocyte-derived CD31+/CD41− microvesicles in sepsis
title_sort hemofiltration induces generation of leukocyte derived cd31 cd41 microvesicles in sepsis
topic Sepsis
Microvesicles
Microparticles
Hemofiltration
Continuous veno-venous hemofiltration
Renal replacement therapy
url http://link.springer.com/article/10.1186/s13613-017-0312-3
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