{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:07:12Z","timestamp":1785409632217,"version":"3.56.0"},"reference-count":26,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2021YFC2701700"],"award-info":[{"award-number":["2021YFC2701700"]}]},{"name":"The National Key Research and Development Program of China","award":["2021YFC2701703"],"award-info":[{"award-number":["2021YFC2701703"]}]},{"name":"Beijing Municipal Administration of Hospitals Incubating Program","award":["PX2024025"],"award-info":[{"award-number":["PX2024025"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82100408"],"award-info":[{"award-number":["82100408"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82370400"],"award-info":[{"award-number":["82370400"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Background:Numerous studies have demonstrated that both cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) are often associated with adverse outcomes or immune dysregulation when platelet counts decline during support. Moreover, the severity of thrombocytopenia generally correlates with a worse clinical prognosis. However, the underlying mechanisms remain incompletely understood. Previous research has attributed this phenomenon to hemodynamic alterations during CPB and ECMO, as well as anticoagulant-induced abnormal platelet activation. Based on our clinical observations, we question the completeness of this explanation and propose an alternative hypothesis: sustained platelet activation during ECMO serves as an initiating factor that contributes to both progressive thrombocytopenia and immune dysfunction throughout the support period.Methods:We investigated platelet activation status, degranulation capacity, and T cell subset dynamics in patients receiving ECMO support. Flow cytometry was used to assess platelet surface markers, reticulated platelet proportions, and T cell subset distributions.Results:We demonstrate that platelets exhibit excessive activation during ECMO, accompanied by a gradual decline in their degranulation capacity. Notably, even with an increased proportion of newly formed platelets, this functional impairment persists. Furthermore, we observed significant alterations in Helper T cell Type 1 (Th1) and CD8+ T cell populations during ECMO support.Conclusions:Our findings suggest that aberrantly activated platelets during ECMO amplify the specific recognition of platelet antigens by CD8+ T cells via modulating the differentiation bias of CD4+ T cells, particularly Th1 cells, ultimately leading to platelet depletion. These results suggest that early interventions targeting abnormal platelet activation may represent a potentially effective therapeutic strategy to mitigate ECMO-associated thrombocytopenia.<\/jats:p>","DOI":"10.31083\/rcm49903","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:31:43Z","timestamp":1785407503000},"source":"Crossref","is-referenced-by-count":0,"title":["Immunothrombotic Dysregulation in Pediatric Patients Receiving Veno-arterial ECMO After Cardiac Surgery: Insights From Platelet Activation and T Cell Immune Profiling"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4492-0522","authenticated-orcid":true,"given":"Junfeng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shengjing Hospital, China Medical University, 110801 Shenyang, Liaoning, China"},{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongtao","family":"Du","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xin","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-0492","authenticated-orcid":true,"given":"Xiaotong","family":"Hou","sequence":"additional","affiliation":[{"name":"Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, 100054 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref1","unstructured":"Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minnesota Medicine. 1954; 37: 171\u201385; passim."},{"key":"ref2","unstructured":"Vyas A, Bishop MA. Extracorporeal Membrane Oxygenation in Adults. StatPearls: Treasure Island (FL). 2022."},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Friedrichson B, Mutlak H, Zacharowski K, Piekarski F. Insight into ECMO, mortality and ARDS: a nationwide analysis of 45,647 ECMO runs. Critical Care (London, England). 2021; 25: 38.","DOI":"10.1186\/s13054-021-03463-2"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, et al. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Annals of Intensive Care. 2016; 6: 97.","DOI":"10.1186\/s13613-016-0196-7"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Doyle AJ, Hunt BJ, Sanderson B, Zhang J, Mak SM, Benedetti G, et al. A Comparison of Thrombosis and Hemorrhage Rates in Patients With Severe Respiratory Failure Due to Coronavirus Disease 2019 and Influenza Requiring Extracorporeal Membrane Oxygenation. Critical Care Medicine. 2021; 49: e663\u2013e672.","DOI":"10.1097\/CCM.0000000000004971"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Tanabe M, Hosokawa K, Nguyen MAT, Nakagawa N, Maruyama K, Tsuji N, et al. The GPI-anchored protein CD109 protects hematopoietic progenitor cells from undergoing erythroid differentiation induced by TGF-\u03b2. Leukemia. 2022; 36: 847\u2013855.","DOI":"10.1038\/s41375-021-01463-3"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Goudswaard LJ, Williams CM, Khalil J, Burley KL, Hamilton F, Arnold D, et al. Alterations in platelet proteome signature and impaired platelet integrin \u03b1IIb\u03b23 activation in patients with COVID-19. Journal of Thrombosis and Haemostasis : JTH. 2023; 21: 1307\u20131321.","DOI":"10.1016\/j.jtha.2023.01.018"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Mansour A, Roussel M, Gaussem P, N\u00e9delec-Gac F, Pontis A, Fl\u00e9cher E, et al. Platelet Functions During Extracorporeal Membrane Oxygenation. Platelet-Leukocyte Aggregates Analyzed by Flow Cytometry as a Promising Tool to Monitor Platelet Activation. Journal of Clinical Medicine. 2020; 9: 2361.","DOI":"10.3390\/jcm9082361"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Wang L, Shao J, Shao C, Wang H, Jia M, Hou X. The Relative Early Decrease in Platelet Count Is Associated With Mortality in Post-cardiotomy Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation. Frontiers in Medicine. 2021; 8: 733946.","DOI":"10.3389\/fmed.2021.733946"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Vrbensky JR, Nazy I, Clare R, Larch\u00e9 M, Arnold DM. T cell-mediated autoimmunity in immune thrombocytopenia. European Journal of Haematology. 2022; 108: 18\u201327.","DOI":"10.1111\/ejh.13705"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Guo L, Shen S, Rowley JW, Tolley ND, Jia W, Manne BK, et al. Platelet MHC class I mediates CD8+ T-cell suppression during sepsis. Blood. 2021; 138: 401\u2013416.","DOI":"10.1182\/blood.2020008958"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Rawish E, Nording H, M\u00fcnte T, Langer HF. Platelets as Mediators of Neuroinflammation and Thrombosis. Frontiers in Immunology. 2020; 11: 548631.","DOI":"10.3389\/fimmu.2020.548631"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Noh JY. Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications. International Journal of Molecular Sciences. 2021; 22: 9615.","DOI":"10.3390\/ijms22179615"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, et al. New gene functions in megakaryopoiesis and platelet formation. Nature. 2011; 480: 201\u2013208.","DOI":"10.1038\/nature10659"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Polasky C, Wendt F, Pries R, Wollenberg B. Platelet Induced Functional Alteration of CD4+ and CD8+ T Cells in HNSCC. International Journal of Molecular Sciences. 2020; 21: 7507.","DOI":"10.3390\/ijms21207507"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Rauch A, Dupont A, Rosa M, Desvages M, Le Tanno C, Abdoul J, et al. Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia. Circulation Research. 2023; 133: 826\u2013841.","DOI":"10.1161\/CIRCRESAHA.123.322752"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Hu M, Lu Y, Wang S, Zhang Z, Qi Y, Chen N, et al. CD63 acts as a functional marker in maintaining hematopoietic stem cell quiescence through supporting TGF\u03b2 signaling in mice. Cell Death and Differentiation. 2022; 29: 178\u2013191.","DOI":"10.1038\/s41418-021-00848-2"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Roeser A, Moulis G, Ebbo M, Terriou L, Poullot E, Lioger B, et al. Characteristics, management and outcome of acquired amegakaryocytic thrombocytopenia. British Journal of Haematology. 2022; 198: 595\u2013599.","DOI":"10.1111\/bjh.18235"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Liu C, Wu D, Xia M, Li M, Sun Z, Shen B, et al. Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2021; 8: e2100921.","DOI":"10.1002\/advs.202100921"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Revel-Vilk S, Naamad M, Frydman D, Freund MR, Dinur T, Istaiti M, et al. Platelet Activation and Reactivity in a Large Cohort of Patients with Gaucher Disease. Thrombosis and Haemostasis. 2022; 122: 951\u2013960.","DOI":"10.1055\/a-1642-4206"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Klaeske K, Dieterlen MT, Eifert S, Scholz U, Garbade J, Jawad K, et al. Device-induced platelet dysfunction in patients after left ventricular assist device implantation. Journal of Thrombosis and Haemostasis : JTH. 2021; 19: 1331\u20131341.","DOI":"10.1111\/jth.15279"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Genty T, Burguburu S, Imbert A, Roman C, Camille W, Th\u00e8s J, et al. Circuit change during extracorporeal membrane oxygenation: single-center retrospective study of 48 changes. Critical Care (London, England). 2023; 27: 219.","DOI":"10.1186\/s13054-023-04503-9"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Li WJ, Peng YX, Zhao LQ, Wang HY, Liu W, Bai K, et al. T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass. Pediatric Research. 2024; 95: 227\u2013232.","DOI":"10.1038\/s41390-023-02765-1"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Paletta A, Di Diego Garc\u00eda F, Varese A, Erra Diaz F, Garc\u00eda J, Cisneros JC, et al. Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism. British Journal of Haematology. 2022; 197: 283\u2013292.","DOI":"10.1111\/bjh.18062"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Manfredi AA, Ramirez GA, Godino C, Capobianco A, Monno A, Franchini S, et al. Platelet Phagocytosis via P-selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis. Arthritis & Rheumatology (Hoboken, N.J.). 2022; 74: 318\u2013328.","DOI":"10.1002\/art.41926"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Johnson JE, McGuone D, Xu ML, Jane-Wit D, Mitchell RN, Libby P, et al. Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis: Correlation with Neutrophil but Not Endothelial Activation. The American Journal of Pathology. 2022; 192: 112\u2013120.","DOI":"10.1016\/j.ajpath.2021.09.004"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/7\/10.31083\/RCM49903","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:31:54Z","timestamp":1785407514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/7\/10.31083\/RCM49903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"alternative-id":["S1530-6550(26)02328-8"],"URL":"https:\/\/doi.org\/10.31083\/rcm49903","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"article-number":"49903"}}