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      Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?

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          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.

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          Most cited references36

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          Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps.

          Increasing evidence implicates both platelets and neutrophils in the formation, stabilization, and growth of peripheral and coronary thrombi. Neutrophil extracellular traps (NETs) play a key role. The early events in the deregulated cross-talk between platelets and neutrophils are poorly characterized.
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            Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation.

            Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin-dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA(2) formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.
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              A meta-analysis of complications and mortality of extracorporeal membrane oxygenation.

              To comprehensively assess published peer-reviewed studies related to extracorporeal membrane oxygenation (ECMO), focusing on outcomes and complications of ECMO in adult patients. Systematic review and meta-analysis. MEDLINE/PubMed was searched for articles on complications and mortality occurring during or after ECMO. Included studies had more than 100 patients receiving ECMO and reported in detail fatal or nonfatal complications occurring during or after ECMO. Primary outcome was mortality at the longest follow-up available; secondary outcomes were fatal and non-fatal complications. Twelve studies were included (1763 patients), mostly reporting on venoarterial ECMO. Criteria for applying ECMO were variable, but usually comprised acute respiratory failure, cardiogenic shock or both. After a median follow-up of 30 days (1st-3rd quartile, 30-68 days), overall mortality was 54% (95% CI, 47%-61%), with 45% (95% CI, 42%-48%) of fatal events occurring during ECMO and 13% (95% CI, 11%-15%) after it. The most common complications associated with ECMO were: renal failure requiring continuous venovenous haemofiltration (occurring in 52%), bacterial pneumonia (33%), any bleeding (33%), oxygenator dysfunction requiring replacement (29%), sepsis (26%), haemolysis (18%), liver dysfunction (16%), leg ischaemia (10%), venous thrombosis (10%), central nervous system complications (8%), gastrointestinal bleeding (7%), aspiration pneumonia (5%), and disseminated intravascular coagulation (5%). Even with conditions usually associated with a high chance of death, almost 50% of patients receiving ECMO survive up to discharge. Complications are frequent and most often comprise renal failure, pneumonia or sepsis, and bleeding.
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                Author and article information

                Contributors
                karla.lehle@ukr.de
                Journal
                Artif Organs
                Artif Organs
                10.1111/(ISSN)1525-1594
                AOR
                Artificial Organs
                John Wiley and Sons Inc. (Hoboken )
                0160-564X
                1525-1594
                30 July 2019
                November 2019
                : 43
                : 11 ( doiID: 10.1111/aor.v43.11 )
                : 1065-1076
                Affiliations
                [ 1 ] Department of Cardiothoracic Surgery University Medical Center Regensburg Regensburg Germany
                [ 2 ] Department of Internal Medicine II University Medical Center Regensburg Regensburg Germany
                [ 3 ] Department of Anesthesiology University Medical Center Regensburg Regensburg Germany
                [ 4 ] Regensburg Center of Biomedical Engineering Ostbayerische Technische Hochschule Regensburg Germany
                Author notes
                [*] [* ] Correspondence

                Karla Lehle, Department of Cardiothoracic Surgery, University Medical Center Regensburg, Franz‐Josef‐Strauss‐Allee 11, Regensburg 93042, Germany.

                Email: karla.lehle@ 123456ukr.de

                Author information
                https://orcid.org/0000-0001-9350-3368
                https://orcid.org/0000-0002-5509-9760
                https://orcid.org/0000-0002-5779-7714
                https://orcid.org/0000-0002-8036-7173
                https://orcid.org/0000-0001-8856-4094
                Article
                AOR13513
                10.1111/aor.13513
                6899554
                31192471
                e3205b40-c363-4301-9974-f28afa7d38af
                © 2019 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organ and Transplantation (ICAOT)

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 14 March 2019
                : 05 June 2019
                : 06 June 2019
                Page count
                Figures: 6, Tables: 3, Pages: 12, Words: 14273
                Categories
                Main Text Article
                Main Text Articles
                Custom metadata
                2.0
                November 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.2 mode:remove_FC converted:05.12.2019

                Transplantation
                extracorporeal membrane oxygenation,liver dysfunction,shear stress,sofa score,thrombogenesis,von willebrand factor

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