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Background: Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO., Methods: A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange., Results: Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/μL vs. 5.9 (5.4/6.3) ng/μL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged., Conclusion: Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Patients with severe coronavirus disease-19 (COVID-19)-associated acute respiratory distress on venovenous extracorporeal lung support (V-V ECLS) showed a high incidence of vascular as well as ECLS-related thrombotic complications. The latter may influence the outcome of the patients., Methods: This is a retrospective monocentric study on prospectively collected data of technical complications including 69 adult COVID-19 patients on V-V ECLS (ECLS Registry, March 2020 until April 2021) without and with system exchanges. Alterations in ECLS-specific data, hemolysis, coagulation, and hemostasis parameters were analyzed., Results: Every second COVID-19 patient on V-V ECLS developed technical complications. Optimized ECLS management at our ECLS center reduced cases of acute clot formation (pump head thrombosis, acute oxygenator thrombosis) (17%), and allowed early identification of progressive clotting processes (worsened gas transfer, coagulation disorder) (14%, 54%) with a significant overhang of hyperfibrinolysis (37%). Although COVID-19 disease and technical complications caused the prolonged length of stay at the intensive care unit and ECLS support times, the proportion of successful weaning and survival rates were comparable with patients without system exchange., Conclusion: The survival of ECLS patients with COVID-19 was independent of the requirement for system exchange due to technical-induced coagulation disorders. Close monitoring for circuit clotting is mandatory in COVID-19 patients and is one prerequisite for successful organ support in these difficult patients., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots-in particular, the presence of von Willebrand factor (vWF)-may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti-vWF and anti-P-selectin) and counterstained with 4',6-diamidino-2-phenylindole. The extent of vWF-loading was correlated with patient and technical data. While 12 MOs showed low vWF-loadings, 9 MOs showed high vWF-loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF-fibers/"cobwebs," leukocytes, platelet-leukocyte aggregates (PLAs), and P-selectin-positive platelet aggregates were independent of the extent of vWF-loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high-molecular-weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy., (© 2019 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organ and Transplantation (ICAOT).)

Multipotent progenitor cells were mobilized during pediatric extracorporeal membrane oxygenation (ECMO). We hypothesize that these cells also adhered onto polymethylpentene (PMP) fibers within the membrane oxygenator (MO) during adult ECMO support. Mononuclear cells were removed from the surface of explanted PMP-MOs (n = 16). Endothelial-like outgrowth and mesenchymal-like cells were characterized by flow cytometric analysis using different surface markers. Spindle-shaped attaching cells were identified early, but without proliferative activity. After long-term cultivation palisading type or cobblestone-type outgrowth cells with high proliferative activity appeared and were characterized as (i) leukocytoid CD45+/CD31+ (CD133+/VEGFR-II+/CD90+/CD14+/CD146dim/CD105dim); (ii) endothelial-like CD45-/CD31+ (VEGF-RII+/CD146+/CD105+/CD133-/CD14-/CD90-); and (iii) mesenchymal-like cells CD45-/CD31- (CD105+/CD90+/CD133dim/VEGFR-II-/CD146-/CD14-). The distribution of the cell populations depended on the MO and cultivation time. Endothelial-like cells formed capillary-like structures and did uptake Dil-acetylated low-density lipoprotein. Endothelial- and mesenchymal-like cells adhered on the surface of PMP-MOs. Further research is needed to identify the clinical relevance of these cells., (Copyright © 2015 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organs and Transplantation (ICAOT).)

Thrombosis inside the membrane oxygenator (MO) is a critical complication during venovenous extracorporeal membrane oxygenation (ECMO). The aim of this study was to prove if thrombotic clots manifest within the MO when D-dimer levels are elevated over a long-term period. Heparin-coated polymethylpentene MOs (n = 13) were exchanged due to high plasma D-dimer levels. Clot volume was calculated using multidetector computed tomography (MDCT). Coagulation parameters and MO function were analyzed before and after MO exchange. Before MO exchange, D-dimer levels increased significantly in each patient (11.5 [6.5-15.5] mg/L to 35.0 [34-35] mg/L, P ≤ 0.001). High levels of D-dimers were tolerated for 1 to 6 days. Additionally, fibrinogen concentration (n = 8) and platelet count decreased (n = 8). Within 48 h after exchange, D-dimer levels decreased significantly (n = 11, 12 [8-16] mg/L, P = 0.004). Fibrinogen concentration and platelet counts increased. Clots were found in all MOs in the inlet part of the device. Clot volume (16-106 cm(3) ) did not correlate with MO support time but increased significantly when high D-dimer levels were accepted for >2 days. An increase or high levels of D-dimers in absence of other explaining pathology during ECMO therapy reflected coagulation activity within the MO. Evidence of clots within the MO at high D-dimer levels and decrease after exchange underline the relevance of D-dimer testing during ECMO treatment. Besides, surveillance of MOs during ongoing ECMO therapy will help to predict clot formation, and to avoid system-induced coagulation disorders as well as critical situations., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Membrane oxygenator (MO) failure is a known hazard during venovenous extracorporeal membrane oxygenation (v-v ECMO) therapy. Knowledge about technical and performance details of different ECMO systems (Maquet, Rastatt, Germany; Medos, Stolberg, Germany; Sorin, Modena, Italy) licensed for adults with acute lung failure might improve their handling. This retrospective study comprises 186 adult patients (Regensburg ECMO Registry) treated with v-v ECMO. Flow dynamic data were used to analyze the performance of different blood pumps, cannula types, and MOs to maintain an adequate blood flow (1-5 L/min). Usage of the Medos ECMO system in critically ill patients required a higher pump speed and generated a higher pressure drop across the MO (dpMO), however, without an increase in free plasma hemoglobin. The dpMO depended on the type of MO and increased with blood flow as expected. Type-specific normal values are reported. A distinct increase in dpMO above normal values within 1 day required an immediate MO exchange. This was an infrequent technical complication (3%). Finally, pressure-flow performance of single dual-lumen cannulas (27 Fr) was comparable with small single-lumen cannulas (15 Fr), without an increased risk of technical-induced hemolysis. Despite different performances, all current commercially available adult v-v ECMO systems produce adequate blood flow without an increased risk in technical-induced hemolysis. Familiarity with the specific properties of individual systems allows early detection of technical complications. Additionally, the choice of an adequate cannula requires a closer consideration of the individual patient situation., (Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Extracorporeal membrane oxygenation (ECMO) is the ultimate treatment option to improve gas exchange and decrease the aggressiveness of mechanical ventilation in septic patients with uncontrolled severe lung failure. However, potential microbiological colonization of the artificial surfaces of membrane oxygenator (MO) remains a critical issue in patients with bacteremia. The current study investigates the risk of MO infection in 10 consecutive septic patients on long-term treatment with ECMO. The flushing fluids of all investigated MOs were sterile. After incubation with nutrient solution for 14 days in one MO Enterococci spp. were isolated. In the patient concerned, a diffuse, unaccountable bleeding diathesis had developed, which stopped after exchange of the MO. Analysis of clinical parameters showed that D dimers had increased and fibrinogen levels had decreased before exchange of this MO, but standard markers of infection had remained unremarkable. In conclusion, circuit infection may be a potential cause for unexplained clinical deterioration of patients on ECMO, which therefore should be considered as an indication for exchange of the device., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)