TY - JOUR A1 - Philipp, Alois A1 - de Somer, Filip A1 - Foltan, Maik A1 - Bredthauer, Andre A1 - Krenkel, Lars A1 - Zeman, Florian A1 - Lehle, Karla T1 - Life span of different extracorporeal membrane systems for severe respiratory failure in the clinical practice JF - PLOS ONE N2 - Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010-2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30%. The median (IQR) life span was 9 (6-12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange. KW - Equipment Failure Analysis/statistics & numerical data KW - Extracorporeal Membrane Oxygenation/instrumentation KW - Membrane/classification/standards/statistics & numerical data KW - Primary Health Care/statistics & numerical data KW - Respiratory Distress Syndrome/therapy KW - Retrospective Studies KW - Severity of Illness Index KW - Time factors KW - MULTIDETECTOR COMPUTED-TOMOGRAPHY KW - THROMBOTIC DEPOSITS KW - ECMO SYSTEMS KW - Flow KW - OXYGENATION Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0198392 VL - 13 IS - 6 SP - 1 EP - 10 PB - PLOS ER - TY - RPRT A1 - Steiger, Tamara A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Gruber, Michael A1 - Bredthauer, Andre A1 - Krenkel, Lars A1 - Birkenmaier, Clemens A1 - Lehle, Karla T1 - Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients? N2 - 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. Y1 - 2019 ER - TY - JOUR A1 - Lingel, Maximilian P. A1 - Haus, Moritz A1 - Paschke, Lukas A1 - Foltan, Maik A1 - Lubnow, Matthias A1 - Gruber, Michael A1 - Krenkel, Lars A1 - Lehle, Karla T1 - Clinical relevance of cell-free DNA during venovenous extracorporeal membrane oxygenation JF - Artificial organs N2 - 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. KW - blood KW - cell- free DNA KW - coagulation KW - ECMO KW - inflammation KW - neutrophil extracellular traps Y1 - 2023 U6 - https://doi.org/10.1111/aor.14616 SN - 1525-1594 VL - 47 IS - 11 SP - 1720 EP - 1731 PB - Wiley ER - TY - JOUR A1 - Foltan, Maik A1 - Dinh, D. A1 - Gruber, Michael A1 - Müller, Thomas A1 - Hart, C. A1 - Krenkel, Lars A1 - Schmid, C. A1 - Lehle, Karla T1 - Incidence of neutrophil extracellular traps (NETs) in different membrane oxygenators: pilot in vitro experiments in commercially available coated membranes JF - Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs N2 - Neutrophil extracellular traps (NETs) were detected in blood samples and in cellular deposits of oxygenator membranes during extracorporeal membrane oxygenation (ECMO) therapy and may be responsible for thrombogenesis. The aim was to evaluate the effect of the base material of gas fiber (GF, polymethylpentene) and heat exchange (HE) membranes and different antithrombogenic coatings on isolated granulocytes from healthy volunteers under static culture conditions. Contact of granulocytes with membranes from different ECMO oxygenators (with different surface coatings) and uncoated-GFs allowed detection of adherent cells and NETotic nuclear structures (normal, swollen, ruptured) using nuclear staining. Flow cytometry was used to identify cell activation (CD11b/CD62L, oxidative burst) of non-adherent cells. Uncoated-GFs were used as a reference. Within 3 h, granulocytes adhered to the same extent on all surfaces. In contrast, the ratio of normal to NETotic cells was significantly higher for uncoated-GFs (56-83%) compared to all coated GFs (34-72%) (p < 0.001) with no difference between the coatings. After material contact, non-adherent cells remained vital with unchanged oxidative burst function and the proportion of activated cells remained low. The expression of activation markers was independent of the origin of the GF material. In conclusion, the polymethylpentene surfaces of the GFs already induce NET formation. Antithrombogenic coatings can already reduce the proportion of NETotic nuclei. However, it cannot be ruled out that NET formation can induce thrombotic events. Therefore, new surfaces or coatings are required for future ECMO systems and long-term implantable artificial lungs. Y1 - 2025 U6 - https://doi.org/10.1007/s10047-024-01486-4 ER - TY - JOUR A1 - Steiger, Tamara A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Gruber, Michael A1 - Bredthauer, Andre A1 - Krenkel, Lars A1 - Birkenmaier, Clemens A1 - Lehle, Karla T1 - Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients? JF - Artificial Organs N2 - 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. KW - ECMO KW - PLATELET ACTIVATION KW - THROMBOSIS KW - BLOOD FLOW KW - INFLAMMATION Y1 - 2019 U6 - https://doi.org/10.1111/aor.13513 SN - 1525-1594 VL - 43 IS - 11 SP - 1065 EP - 1076 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Haus, Moritz A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Lingel, Maximilian P. A1 - Krenkel, Lars A1 - Gruber, Michael A1 - Lehle, Karla T1 - Neutrophil extracellular traps -a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation N2 - Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased iL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients. KW - Neutrophil extracellular traps (NET) KW - Immunoflorescence KW - Thrombocytopenia KW - Extracorporeal membrane oxygenation (ECMO) KW - Sepsis KW - immunothrombosis KW - Coagulation disorder Y1 - 2024 UR - https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1339235/abstract U6 - https://doi.org/10.3389/fimmu.2024.1339235 VL - 15 PB - frontiers ER -