TY - RPRT A1 - Steiger, Tamara A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Gruber, Michael Andreas 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 - Steiger, Tamara A1 - Foltan, Maik A1 - Philipp, Alois A1 - Mueller, Thomas A1 - Gruber, Michael Andreas 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 - 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 - JOUR A1 - Wagner, Maria Stella A1 - Kranz, Michael A1 - Krenkel, Lars A1 - Pointner, Daniel A1 - Foltan, Maik A1 - Lubnow, Matthias A1 - Lehle, Karla ED - Becatti, Matteo T1 - Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs JF - Frontiers in Medicine N2 - Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-oftherapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4′, 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs. KW - ECMO KW - membrane lung KW - µCT KW - MDCT KW - shear induced clotting KW - vWF KW - histological evaluation Y1 - 2024 U6 - https://doi.org/10.3389/fmed.2024.1416319 IS - 11 PB - Frontiers ER -