@article{WagnerKranzKrenkeletal., author = {Wagner, Maria Stella and Kranz, Michael and Krenkel, Lars and Pointner, Daniel and Foltan, Maik and Lubnow, Matthias and Lehle, Karla}, title = {Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs}, series = {Frontiers in Medicine}, journal = {Frontiers in Medicine}, number = {11}, editor = {Becatti, Matteo}, publisher = {Frontiers}, doi = {10.3389/fmed.2024.1416319}, abstract = {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.}, language = {en} } @article{HausFoltanPhilippetal., author = {Haus, Moritz and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Lingel, Maximilian P. and Krenkel, Lars and Gruber, Michael and Lehle, Karla}, title = {Neutrophil extracellular traps -a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation}, volume = {15}, publisher = {frontiers}, doi = {10.3389/fimmu.2024.1339235}, abstract = {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.}, language = {en} } @misc{KranzWagnerPointneretal., author = {Kranz, Michael and Wagner, Maria Stella and Pointner, Daniel and Waldbauer, Selina and M{\"u}ller, Thomas and Lubnow, Matthias and Foltan, Maik and Krenkel, Lars and Lehle, Karla}, title = {Polymeric Embedding of Membrane Lungs: A Novel Method for Histological Investigations of Intra-Device Clot Formation}, series = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, journal = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, language = {en} } @misc{KoesterKranzWagneretal., author = {K{\"o}ster, Leonie and Kranz, Michael and Wagner, Maria Stella and Foltan, Maik and M{\"u}ller, Thomas and Lubnow, Matthias and Krenkel, Lars and Lehle, Karla}, title = {Histological Investigations of Intra-Device Clot Formation in ECMO Pumps}, series = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, journal = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, language = {en} }