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Hemofiltration induces generation of leukocyte-derived CD31+/CD41- microvesicles in sepsis
Georg Franz Lehner1, Ulrich Harler1, Clemens Feistritzer2
1Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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.
Insights
Continuous veno-venous hemofiltration (CVVH) in sepsis patients increases certain microvesicles (MV) indicating leukocyte activation. While CVVH clears some MVs and tissue factor (TF), it also induces release of larger MVs, suggesting careful filtration fraction management is needed.
Area of Science:
- Critical Care Medicine
- Nephrology
- Immunology
Background:
- Microvesicles (MV) are linked to cellular activation and inflammation.
- Hemofiltration (CVVH) purifies blood for renal failure and sepsis, but artificial membranes can induce inflammation.
- Increased MVs are observed in chronic dialysis patients.
Purpose of the Study:
- To investigate how CVVH affects MV composition and levels in critically ill sepsis patients.
- To determine if blood passage through a hemofilter alters MV profiles.
Main Methods:
- Collected pre- and post-hemofilter blood and ultrafiltrate from sepsis patients undergoing CVVH.
- Analyzed MV subtypes using high-sensitivity flow cytometry.
- Quantified tissue factor (TF) levels and MV-associated TF activity, correcting for hemoconcentration.
Main Results:
- Observed a significant increase in leukocyte-derived CD31+/CD41- MV post-hemofilter.
- Found no significant changes in platelet-derived or AnnexinV-binding MV.
- Detected reductions in overall MV activity and TF levels post-hemofilter.
- Correlated MV subtype increments with filtration fraction (FF).
Conclusions:
- CVVH clears some small MVs but not larger ones, and it induces leukocyte activation.
- Increased MV subtypes correlate with FF, supporting lower filtration rates.
- CVVH partially clears TF via ultrafiltration.
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