@article{PhilippdeSomerFoltanetal., author = {Philipp, Alois and de Somer, Filip and Foltan, Maik and Bredthauer, Andre and Krenkel, Lars and Zeman, Florian and Lehle, Karla}, title = {Life span of different extracorporeal membrane systems for severe respiratory failure in the clinical practice}, series = {PLOS ONE}, volume = {13}, journal = {PLOS ONE}, number = {6}, publisher = {PLOS}, doi = {10.1371/journal.pone.0198392}, pages = {1 -- 10}, abstract = {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.}, language = {en} } @techreport{Krenkel, author = {Krenkel, Lars}, title = {Investigation of the impact of vortex generators on the shock/boundary-layer interaction}, issn = {1434-8454}, abstract = {Comprehensive experimental and numerical parameter studies on the impact of isolated vortex generator pairs and complex vortex generator arrays onto a strong shock-/boundary layer interaction are presented within the context of this thesis. The effects of vortices, especially as they interact with each other are discussed in terms of their impact on the boundary layer development, the shock characteristics and the overall aerodynamic performance of the aerofoil. The presented results have been obtained from wind tunnel experiments with a simple flat plate with superimposed pressure gradient as well as with a more comprehensive model of a supercritical transonic aerofoil. In addition complex numerical parameter studies on a supercritical aerofoil in free stream conditions have been conducted. This work is designed for gaining a better understanding of the fundamental mechanisms of vortex generator/shock/boundary-layer interaction in order to achieve improved flight performance in terms of drag reduction, avoidance or at least postponement of separation onset and shock oscillation as well as lift improvement by application of optimised vortex generator configurations.}, language = {en} } @article{DiermeierSindersbergerKrenkeletal., author = {Diermeier, Andreas and Sindersberger, Dirk and Krenkel, Lars and Rosell, X. C. and Monkman, Gareth J.}, title = {Controllable Magnetoactive Polymer Conduit}, series = {The Open Mechanical Engineering Journal}, volume = {12}, journal = {The Open Mechanical Engineering Journal}, number = {1}, publisher = {Bentham}, pages = {192 -- 200}, abstract = {Objective: Magneto-active Polymers (MAP) are smart materials whose mechanical characteristics, such as elastic and shear moduli, may be controllable by means of an externally applied magnetic field. Methods: Various additives may be used to influence the characteristics of the polymer matrix whilst a suspension of soft and/or hard magnetic particles determine the magnetic properties of the composite. Both pre-cure and post-cure magnetization is possible. Results: A range of control strategies have been investigated for evaluation of the system using fluids of differing kinematic viscosity. Conclusion: Depending on the degree of magnetic field homogeneity, magneto-deformation and magnetostriction contribute to MAP actuation. This paper presents a novel application in the form of a peristaltic MAP tube system, applicable to flow control and pumping of hemorheological fluids in blood circulatory systems for biomedical research purposes.}, language = {en} } @techreport{SteigerFoltanPhilippetal., type = {Working Paper}, author = {Steiger, Tamara and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Gruber, Michael and Bredthauer, Andre and Krenkel, Lars and Birkenmaier, Clemens and Lehle, Karla}, title = {Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?}, abstract = {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.}, language = {en} } @book{Krenkel, author = {Krenkel, Lars}, title = {Untersuchung des Einflusses von Wirbelgeneratoren auf die Stoß-/Grenzschicht-Wechselwirkung}, publisher = {Rheinisch-Westf{\"a}lische Technische Hochschule Aachen}, address = {Aachen}, issn = {1434-8454}, abstract = {Im Rahmen dieser Arbeit werden experimentelle und numerische Parameterstudien von einzelnen Wirbelgeneratorpaaren und komplexeren Wirbelgeneratoranordnungen bez{\"u}glich ihres Einflusses auf eine starke Stoß-/Grenzschicht-Wechselwirkung vorgestellt. Dabei werden die Einfl{\"u}sse von Wirbeln, insbesondere die Auswirkungen ihrer Wechselwirkungen untereinander, auf das Grenzschichtverhalten, die Stoßcharakteristik und insgesamt auf die aerodynamische Leistung des betrachteten Profils diskutiert. Dazu wurden sowohl Windkanalversuche am einfachen Modell einer ebenen Platte mit aufgepr{\"a}gtem Druckgradienten sowie an einem Modell eines superkritischen transsonischen Profils durchgef{\"u}hrt. Erg{\"a}nzend wurden komplexe nume-rische Parameteruntersuchungen an einem Profil in freier Anstr{\"o}mung ausgef{\"u}hrt. Es ist das Ziel, ein besse-res Verst{\"a}ndnis der Mechanismen der Wirbelgenerator-/Stoß-/Grenzschicht-Wechselwirkung zu gewinnen, um durch optimierte Anwendung von Wirbelgeneratoren eine Verbesserung der Flugleistungen erzielen zu k{\"o}nnen. Die Schwerpunkte liegen dabei auf der Reduktion des Widerstandes, der Vermeidung bzw. Verz{\"o}ge-rung von Str{\"o}mungsabl{\"o}sung und Stoßschwingung sowie auf der Erh{\"o}hung des Auftriebs.}, language = {de} } @article{StelzerKrenkel, author = {Stelzer, Vera and Krenkel, Lars}, title = {2D numerical investigations derived from a 3D dragonfly wing captured with a high-resolution micro-CT}, series = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {30}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, number = {1}, publisher = {IOS Press}, doi = {10.3233/THC-219010}, pages = {283 -- 289}, abstract = {BACKGROUND: Due to their corrugated profile, dragonfly wings have special aerodynamic characteristics during flying and gliding. OBJECTIVE: The aim of this study was to create a realistic 3D model of a dragonfly wing captured with a high-resolution micro-CT. To represent geometry changes in span and chord length and their aerodynamic effects, numerical investigations are carried out at different wing positions. METHODS: The forewing of a Camacinia gigantea was captured using a micro-CT. After the wing was adapted an error-free 3D model resulted. The wing was cut every 5 mm and 2D numerical analyses were conducted in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, USA). RESULTS: The highest lift coefficient, as well as the highest lift-to-drag ratio, resulted at 0 mm and an angle of attack (AOA) of 5∘. At AOAs of 10∘ or 15∘, the flow around the wing stalled and a K{\´a}rm{\´a}n vortex street behind the wing becomes CONCLUSIONS: The velocity is higher on the upper side of the wing compared to the lower side. The pressure acts vice versa. Due to the recirculation zones that are formed in valleys of the corrugation pattern the wing resembles the form of an airfoil.}, language = {en} } @article{SchecklmannSchmausserKlingeretal., author = {Schecklmann, Martin and Schmausser, Maximilian and Klinger, Felix and Kreuzer, Peter M. and Krenkel, Lars and Langguth, Berthold}, title = {Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil}, series = {scientific reports}, volume = {10}, journal = {scientific reports}, number = {1}, publisher = {Nature}, doi = {10.1038/s41598-020-58034-2}, abstract = {The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27\%) in contrast to the DC coil (about 15\%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.}, language = {en} } @article{TauwaldMichelBrandtetal., author = {Tauwald, Sandra Melina and Michel, Johanna and Brandt, Marie and Vielsmeier, Veronika and Stemmer, Christian and Krenkel, Lars}, title = {Experimental studies and mathematical modeling of the viscoelastic rheology of tracheobronchial mucus from respiratory healthy patients}, series = {Multidisciplinary Respiratory Medicine}, volume = {18}, journal = {Multidisciplinary Respiratory Medicine}, number = {1}, publisher = {PAGEPress}, address = {Pavia, Italy}, issn = {2049-6958}, doi = {10.4081/mrm.2023.923}, pages = {12}, abstract = {BACKGROUND: Tracheobronchial mucus plays a crucial role in pulmonary function by providing protection against inhaled pathogens. Due to its composition of water, mucins, and other biomolecules, it has a complex viscoelastic rheological behavior. This interplay of both viscous and elastic properties has not been fully described yet. In this study, we characterize the rheology of human mucus using oscillatory and transient tests. Based on the transient tests, we describe the material behavior of mucus under stress and strain loading by mathematical models. METHODS: Mucus samples were collected from clinically used endotracheal tubes. For rheological characterization, oscillatory amplitude-sweep and frequency-sweep tests, and transient creep-recovery and stress-relaxation tests were performed. The results of the transient test were approximated using the Burgers model, the Weibull distribution, and the six-element Maxwell model. The three-dimensional microstructure of the tracheobronchial mucus was visualized using scanning electron microscope imaging. RESULTS: Amplitude-sweep tests showed storage moduli ranging from 0.1 Pa to 10000 Pa and a median critical strain of 4 \%. In frequency-sweep tests, storage and loss moduli increased with frequency, with the median of the storage modulus ranging from 10 Pa to 30 Pa, and the median of the loss modulus from 5 Pa to 14 Pa. The Burgers model approximates the viscoelastic behavior of tracheobronchial mucus during a constant load of stress appropriately (R2 of 0.99), and the Weibull distribution is suitable to predict the recovery of the sample after the removal of this stress (R2 of 0.99). The approximation of the stress-relaxation test data by a six-element Maxwell model shows a larger fit error (R2 of 0.91). CONCLUSIONS: This study provides a detailed description of all process steps of characterizing the rheology of tracheobronchial mucus, including sample collection, microstructure visualization, and rheological investigation. Based on this characterization, we provide mathematical models of the rheological behavior of tracheobronchial mucus. These can now be used to simulate mucus flow in the respiratory system through numerical approaches.}, language = {en} } @article{BirkenmaierDorniaLehleetal., author = {Birkenmaier, Clemens and Dornia, Christian and Lehle, Karla and M{\"u}ller, Thomas and Gruber, Michael and Philipp, Alois and Krenkel, Lars}, title = {Analysis of Thrombotic Deposits in Extracorporeal Membrane Oxygenators by High-resolution Microcomputed Tomography: A Feasibility Study}, series = {ASAIO Journal / American Society for Artificial Internal Organs}, volume = {66}, journal = {ASAIO Journal / American Society for Artificial Internal Organs}, number = {8}, publisher = {Lippincott Williams \& Wilkins}, issn = {1538-943X}, doi = {10.1097/MAT.0000000000001089}, pages = {922 -- 928}, abstract = {Coagulative disorders, especially clotting during extracorporeal membrane oxygenation, are frequent complications. Direct visualization and analysis of deposits in membrane oxygenators using computed tomography (CT) may provide an insight into the underlying mechanisms causing thrombotic events. However, the already established multidetector CT1 (MDCT) method shows major limitations. Here, we demonstrate the feasibility of applying industrial micro-CT (μCT) to circumvent these restrictions. Three clinically used membrane oxygenators were investigated applying both MDCT and μCT. The scans were analyzed in terms of clot volume and local clot distribution. As validation, the clot volume was also determined from the fluid volume, which could be filled into the respective used oxygenator compared to a new device. In addition, cross-sectional CT images were compared with crosscut oxygenators. Based on the μCT findings, a morphological measure (sphericity) for assessing clot structures in membrane oxygenators is introduced. Furthermore, by comparing MDCT and μCT results, an augmentation of the MDCT method is proposed, which allows for improved clot volume determination in a clinical setting.}, language = {en} } @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{LingelHausPaschkeetal., author = {Lingel, Maximilian P. and Haus, Moritz and Paschke, Lukas and Foltan, Maik and Lubnow, Matthias and Gruber, Michael and Krenkel, Lars and Lehle, Karla}, title = {Clinical relevance of cell-free DNA during venovenous extracorporeal membrane oxygenation}, series = {Artificial organs}, volume = {47}, journal = {Artificial organs}, number = {11}, publisher = {Wiley}, issn = {1525-1594}, doi = {10.1111/aor.14616}, pages = {1720 -- 1731}, abstract = {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.}, language = {en} } @article{FoltanDinhGruberetal., author = {Foltan, Maik and Dinh, D. and Gruber, Michael and M{\"u}ller, Thomas and Hart, C. and Krenkel, Lars and Schmid, C. and Lehle, Karla}, title = {Incidence of neutrophil extracellular traps (NETs) in different membrane oxygenators: pilot in vitro experiments in commercially available coated membranes}, series = {Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs}, journal = {Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs}, doi = {10.1007/s10047-024-01486-4}, abstract = {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.}, language = {en} } @article{PaschkeFoltanWagneretal., author = {Paschke, Lukas and Foltan, Maik and Wagner, Maria S. and Lubnow, Matthias and Gruber, Michael and Krenkel, Lars and Lehle, Karla}, title = {Clinical Relevance of Platelet-Leukocyte Aggregates and Platelet P-Selectin Expression During Venovenous Extracorporeal Membrane Oxygenation}, series = {ASAIO Journal}, journal = {ASAIO Journal}, number = {April 03}, publisher = {Wolters Kluwer}, issn = {1058-2916}, doi = {10.1097/MAT.0000000000002421}, abstract = {Thrombosis continues to be a significant complication during venovenous extracorporeal membrane oxygenation (V-V ECMO). Platelet activation markers might serve as indicators of inflammation and thrombogenesis. The aim was to identify these markers in ECMO patients. Blood from 10 ECMO patients (before, during, after ECMO) and 11 healthy volunteers were collected to determine platelet-neutrophil-aggregates (PNAs), platelet-monocyte-aggregates (PMAs), fibrinogen-binding, and P-selectin-expression on platelets by flow cytometry. Critical illness was associated with significantly elevated levels of PNAs and PMAs, increased P-selectin expression, reduced fibrinogen-binding, and restricted activation of platelets. Although PNAs and PMAs decreased significantly within 2 hours after the initiation of ECMO and remained at those levels, ECMO did not affect basal P-selectin expression and fibrinogen-binding. These results correlated with coagulation activation. Platelet markers before ECMO were not indicators for an imminent system exchange and end of therapy. In conclusion, platelet dysfunction during ECMO was mainly attributed to the critical illness. Extracorporeal membrane oxygenation support strengthened the restricted response of platelets to exogenous agonists (P-selectin). Furthermore, a decrease in PNAs/PMAs after ECMO started identified a reduced inflammatory response. There was no correlation of analyzed platelet parameters with the incidence of thrombotic complications.}, language = {en} } @article{SteigerFoltanPhilippetal., author = {Steiger, Tamara and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Gruber, Michael and Bredthauer, Andre and Krenkel, Lars and Birkenmaier, Clemens and Lehle, Karla}, title = {Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?}, series = {Artificial Organs}, volume = {43}, journal = {Artificial Organs}, number = {11}, publisher = {Wiley}, address = {Hoboken}, issn = {1525-1594}, doi = {10.1111/aor.13513}, pages = {1065 -- 1076}, abstract = {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.}, language = {en} }