BACKGROUND: Thrombocytopenia is a recognized risk factor for bleeding during extracorporeal membrane oxygenation (ECMO). This study determines the incidence, risk factors, and clinical relevance of thrombocytopenia and platelet transfusions during venovenous (VV) ECMO. METHODS: The multicenter, prospective observational PROTECMO study included 652 adult patients who received VV ECMO for respiratory failure. Thrombocytopenia was classified as mild (100-149·109/L), moderate (50-99·109/L), or severe (< 50·109/L). Bleeding events were evaluated using a modified Bleeding Academy Research Consortium score. Cox proportional hazards and logistic regression analyses were done to identify predictors, and quantify the association between platelet counts and bleeding risk. RESULTS: A total of 182 patients (27.9%) had thrombocytopenia at baseline (mild in 14.7%, moderate in 8.7%, and severe in 4.4%). Thrombocytopenia during ECMO, at least once in 80.2% of patients, was mild in 21.3% of cases, moderate in 32.2%, and severe in 26.7%. A 10·109/L decrease in platelet count was associated with a 3.7% (95% CI: 2.4-5.0%) increase in risk of bleeding. There was no strong evidence of nonlinear relationship within the platelet count range between 25,000 and 300,000. This relation remained consistent across all ECMO weeks. Mild thrombocytopenia increased the risk of experiencing a bleeding event by 61% (hazard ratio (HR) 1.611, 95% CI 1.230-2.109, p = 0.0005), while moderate and severe thrombocytopenia increased the risk by roughly 90% (moderate: HR 1.944 (CI 1.484-2.545), p < 0.0001; severe: HR 1.876 (CI 1.275-2.7680), p = 0.0014). The risk for thrombocytopenia < 100·109/L during ECMO significantly increased with ICU days prior to ECMO start, postoperative admission, immunocompromised state, renal replacement therapy, septic shock, low hemoglobin, and circuit exchange. CONCLUSIONS: Thrombocytopenia is highly prevalent in VV ECMO, and associated with a significant increase in the risk of bleeding, and a reduction in 6-month survival, particularly at platelet counts below 100·109/L. Further research is needed to better define the outcomes associated with specific thresholds for transfusion of platelets.

1st Medical Faculty of the Charles University General University Hospital Prague Czechia Czechia

Adan Hospital Al Ahmadi Governate Hadiya MOH Kuwait

Cardiothoracic Surgery Department Cardiovascular Research Institute Maastricht Maastricht University Medical Center Maastricht University Maastricht Netherlands

Critical Care Department Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Allergy Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN USA

Department of Anaesthesiology and Intensive Care National Medical Institute of the Ministry of Interior and Administration Warszawa Poland

Department of Anesthesia and Intensive Care Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione Via Tricomi 5 Palermo 90133 Italy

Department of Anesthesia Critical Care and Emergency Città della Salute e della Scienza Hospital University of Turin Turin Italy

Department of Anesthesia Intensive Care and Emergency Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Milan Italy

Department of Critical Care Medicine University of Pittsburgh Pittsburgh PA USA

Department of Medicine 1 Intensive Care Unit 13i2 Center of Excellence in Medical Intensive Care Medical University of Vienna Vienna Austria

Department of Medicine Columbia University College of Physicians and Surgeons New York NY USA

Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD USA

ECMO Centre Karolinska Department of Physiology and Pharmacology Karolinska University Hospital Karolinska Institute Stockholm Sweden

Fondazione IRCCS San Gerardo dei Tintori Università degli Studi di Milano Bicocca Monza Italy

Hamad Medical Corporation Doha Qatar

Institute of Cardiometabolism and Nutrition Sorbonne University Paris France

Meijer Heart Center Butterworth Hospital Spectrum Health Grand Rapids Michigan USA

St Vincent's Hospital Sydney University of New South Wales Sydney NSW Australia

Statistics and Data Management Services IRCCS ISMETT Palermo Italy

The University of Oklahoma Health Sciences Center University of Oklahoma Oklahoma City OK USA

UPMCI Palermo Italy

Zobrazit více v PubMed

Martucci G, Giani M, Schmidt M, Tanaka K, Tabatabai A, Tuzzolino F, et al. Anticoagulation and bleeding during Veno-Venous extracorporeal membrane oxygenation: insights from the Protecmo study. Am J Respir Crit Care Med. 2024;209(4):417–26. PubMed

Raasveld SJ, van den Oord C, Schenk J, van den Bergh WM, Oude Lansink-Hartgring A, van der Velde F, et al. The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study. Crit Care. 2023;27(1):321. PubMed PMC

Mansour A, Flecher E, Schmidt M, Rozec B, Gouin-Thibault I, Esvan M, et al. Bleeding and thrombotic events in patients with severe Covid-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study. Intensive Care Med. 2022;48(8):1039–52. PubMed

Lusebrink E, Zimmer S, Schrage B, Dabboura S, Majunke N, Scherer C, et al. Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation. Eur Heart J Acute Cardiovasc Care. 2022;11(4):303–11. PubMed

Abbasi A, Karasu Y, Li C, Sodha NR, Eickhoff C, Ventetuolo CE. Machine learning to predict hemorrhage and thrombosis during extracorporeal membrane oxygenation. Crit Care. 2020;24(1):689. PubMed PMC

Jiritano F, Serraino GF, Ten Cate H, Fina D, Matteucci M, Mastroroberto P, et al. Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis. Intensive Care Med. 2020;46(6):1154–69. PubMed PMC

Mansour A, Roussel M, Gaussem P, Nedelec-Gac F, Pontis A, Flecher E et al. Platelet functions during extracorporeal membrane oxygenation. platelet-Leukocyte aggregates analyzed by flow cytometry as a promising tool to monitor platelet activation. J Clin Med. 2020;9(8):2361. PubMed PMC

Van Den Helm S, Yaw HP, Letunica N, Barton R, Weaver A, Newall F, et al. Platelet phenotype and function changes with increasing duration of extracorporeal membrane oxygenation. Crit Care Med. 2022;50(8):1236–45. PubMed

Panholzer B, Bajorat T, Haneya A, Kowalski D, Juhl D, Rocke A, et al. Acquired von Willebrand syndrome in Ecmo patients: A 3-year cohort study. Blood Cells Mol Dis. 2021;87:102526. PubMed

Hunsicker O, Beck L, Krannich A, Finger T, Prinz V, Spies C, et al. Timing, outcome, and risk factors of intracranial hemorrhage in acute respiratory distress syndrome patients during venovenous extracorporeal membrane oxygenation. Crit Care Med. 2021;49(2):e120–9. PubMed

Abrams D, Baldwin MR, Champion M, Agerstrand C, Eisenberger A, Bacchetta M, et al. Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study. Intensive Care Med. 2016;42(5):844–52. PubMed PMC

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. Front Med (Lausanne). 2021;8:733946. PubMed PMC

Pratt EH, Stokes JW, Fan E. Bleeding and clotting while supported with ecmo: time to move forward. Intensive Care Med. 2022;48(8):1059–61. PubMed

Martucci G, Schmidt M, Agerstrand C, Tabatabai A, Tuzzolino F, Giani M, et al. Transfusion practice in patients receiving Vv Ecmo (Protecmo): a prospective, multicentre, observational study. Lancet Respir Med. 2023;11(3):245–55. PubMed

Schmidt M, Bailey M, Sheldrake J, Hodgson C, Aubron C, Rycus PT, et al. Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score. Am J Respir Crit Care Med. 2014;189(11):1374–82. PubMed

Schmidt M, Zogheib E, Roze H, Repesse X, Lebreton G, Luyt CE, et al. The preserve mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intensive Care Med. 2013;39(10):1704–13. PubMed PMC

Malfertheiner MV, Philipp A, Lubnow M, Zeman F, Enger TB, Bein T, et al. Hemostatic changes during extracorporeal membrane oxygenation: A prospective randomized clinical trial comparing three different extracorporeal membrane oxygenation systems. Crit Care Med. 2016;44(4):747–54. PubMed

Dzierba AL, Roberts R, Muir J, Alhammad A, Schumaker G, Clark J, et al. Severe thrombocytopenia in adults with severe acute respiratory distress syndrome: impact of extracorporeal membrane oxygenation use. ASAIO J. 2016;62(6):710–4. PubMed

Kalbhenn J, Schlagenhauf A, Rosenfelder S, Schmutz A, Zieger B. Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: rapid onset and fast recovery. J Heart Lung Transpl. 2018;37(8):985–91. PubMed

Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018;378(21):1965–75. PubMed

Kochanek M, Kochanek J, Boll B, Eichenauer DA, Beutel G, Bracht H, et al. Veno-venous extracorporeal membrane oxygenation (vv-ecmo) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis. Intensive Care Med. 2022;48(3):332–42. PubMed PMC

Bergman ZR, Wothe JK, Alwan FS, Lofrano AE, Tointon KM, Doucette M, et al. Risk factors of mortality for patients receiving venovenous extracorporeal membrane oxygenation for Covid-19 acute respiratory distress syndrome. Surg Infect (Larchmt). 2021;22(10):1086–92. PubMed

Doyle AJ, Hunt BJ. Current Understanding of how extracorporeal membrane oxygenators activate haemostasis and other blood components. Front Med (Lausanne). 2018;5:352. PubMed PMC

Haus M, Foltan M, Philipp A, Mueller T, Gruber M, Lingel MP, et al. Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation. Front Immunol. 2024;15:1339235. PubMed PMC

Butt SP, Razzaq N, Saleem Y, Cook B, Abdulaziz S. Improving Ecmo therapy: monitoring oxygenator functionality and identifying key indicators, factors, and considerations for changeout. J Extra Corpor Technol. 2024;56(1):20–9. PubMed PMC

Helms J, Curtiaud A, Severac F, Merdji H, Angles-Cano E. Dynamic longitudinal increase in D-dimers: an early predictor of bleeding complications in Ecmo. Intensive Care Med. 2023;49(11):1416–7. PubMed

Giani M, Panigada M. D-dimer and bleeding during ecmo: the chicken and the egg? Intensive Care Med. 2023;49(12):1567–8. PubMed

Genty T, Burguburu S, Imbert A, Roman C, Camille W, Thes J, et al. Circuit change during extracorporeal membrane oxygenation: single-center retrospective study of 48 changes. Crit Care. 2023;27(1):219. PubMed PMC

Buchtele N, Schorgenhofer C, Schwameis M, Jilma B, Schellongowski P, Herkner H, et al. Add-On prostaglandin E(1) in venovenous extracorporeal membrane oxygenation: A randomized, Double-Blind, Placebo-controlled pilot trial. Am J Respir Crit Care Med. 2022;206(2):170–7. PubMed

McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J. 2022;68(3):303–10. PubMed

Esper SA, Welsby IJ, Subramaniam K, John Wallisch W, Levy JH, Waters JH, et al. Adult extracorporeal membrane oxygenation: an international survey of transfusion and anticoagulation techniques. Vox Sang. 2017;112(5):443–52. PubMed

Hoffman KR, Diehl A, Paul E, Burrell AJC. The hematological effects of extracorporeal membrane oxygenator exchange. ASAIO J. 2023;69(7):e308–14. PubMed PMC

Cohn CS. Platelet transfusion refractoriness: how do I diagnose and manage? Hematol Am Soc Hematol Educ Program. 2020;2020(1):527–32. PubMed PMC