Semin Thromb Hemost 2020; 46(01): 062-072
DOI: 10.1055/s-0039-3400273
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

Zhe Amy Fang
1   Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
,
Amir Hassan Navaei
2   Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
,
Lisa Hensch
2   Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
,
Shiu-Ki Rocky Hui
2   Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
3   Department of Pediatrics, Baylor College of Medicine, Houston, Texas
,
Jun Teruya
2   Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
3   Department of Pediatrics, Baylor College of Medicine, Houston, Texas
4   Department of Medicine, Baylor College of Medicine, Houston, Texas
› Author Affiliations
Further Information

Publication History

Publication Date:
13 December 2019 (online)

Abstract

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effects of extracorporeal circuits can also have an undesired consequence of bleeding. Extracorporeal circulation leads to coagulopathy that may require therapy with blood products such as platelets, cryoprecipitate, and plasma in case a patient bleeds. Platelet dysfunction related to exposure to a foreign circuit is a primary concern, as is the development of acquired von Willebrand syndrome, which frequently remains undetected on routine testing. Hemorrhagic complications in ECMO, such as intracranial hemorrhage, pulmonary hemorrhage, and hemithorax, can occur. Hemostatic agents including antifibrinolytics, desmopressin, fibrinogen concentrates, and other factor concentrates may be needed to achieve hemostasis in these often-challenging patients. Managing bleeding on extracorporeal support requires careful monitoring and a thoughtful approach.

 
  • References

  • 1 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76 (09) 1680-1697
  • 2 Besser MW, Ortmann E, Klein AA. Haemostatic management of cardiac surgical haemorrhage. Anaesthesia 2015; 70 (01) (Suppl. 01) 87-95 , e29–e31
  • 3 Khan JH, Green EA, Chang J. , et al. Blood and blood product conservation: results of strategies to improve clinical outcomes in open heart surgery patients at a tertiary hospital. J Extra Corpor Technol 2017; 49 (04) 273-282
  • 4 LaPar DJ, Crosby IK, Ailawadi G. , et al; Investigators for the Virginia Cardiac Surgery Quality Initiative. Blood product conservation is associated with improved outcomes and reduced costs after cardiac surgery. J Thorac Cardiovasc Surg 2013; 145 (03) 796-803 , discussion 803–804
  • 5 Richmond ME, Charette K, Chen JM, Quaegebeur JM, Bacha E. The effect of cardiopulmonary bypass prime volume on the need for blood transfusion after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2013; 145 (04) 1058-1064
  • 6 Miller RD. , ed. Miller's Anesthesia. 8th ed. Philadelphia, PA: Elsevier/Saunders; 2015
  • 7 Matte GS. Perfusion for Congenital Heart Surgery: Notes on Cardiopulmonary Bypass in a Complex Patient Population. Hoboken, NJ: John Wiley & Sons; 2015
  • 8 Grottke O, Fries D, Nascimento B. Perioperatively acquired disorders of coagulation. Curr Opin Anaesthesiol 2015; 28 (02) 113-122
  • 9 Höfer J, Fries D, Solomon C, Velik-Salchner C, Ausserer J. A snapshot of coagulopathy after cardiopulmonary bypass. Clin Appl Thromb Hemost 2016; 22 (06) 505-511
  • 10 Ranucci M, Pistuddi V, Di Dedda U. , et al. Platelet function after cardiac surgery and its association with severe postoperative bleeding: the PLATFORM study. Platelets 2019; 30 (07) 908-914
  • 11 Kaplan JA, Augoustides JGT, Manecke GR, Maus T, Reich DL. , eds. Kaplan's Cardiac Anesthesia: For Cardiac and Noncardiac Surgery. 7th ed. Philadelphia, PA: Elsevier; 2017: 1663
  • 12 O'Gara PT, Kushner FG, Ascheim DD. , et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61 (04) e78-e140
  • 13 Oprea AD, Popescu WM. Perioperative management of antiplatelet therapy. Br J Anaesth 2013; 111 (Suppl. 01) i3-i17
  • 14 Fitchett D, Eikelboom J, Fremes S. , et al. Dual antiplatelet therapy in patients requiring urgent coronary artery bypass grafting surgery: a position statement of the Canadian Cardiovascular Society. Can J Cardiol 2009; 25 (12) 683-689
  • 15 Levy JH, Douketis J, Steiner T, Goldstein JN, Milling TJ. Prothrombin complex concentrates for perioperative vitamin K antagonist and non-vitamin K anticoagulant reversal. Anesthesiology 2018; 129 (06) 1171-1184
  • 16 Erdoes G, Martinez Lopez De Arroyabe B, Bolliger D. , et al. International consensus statement on the peri-operative management of direct oral anticoagulants in cardiac surgery. Anaesthesia 2018; 73 (12) 1535-1545
  • 17 Charlesworth M, Arya R. Direct oral anticoagulants: peri-operative considerations and controversies. Anaesthesia 2018; 73 (12) 1460-1463
  • 18 Arbit B, Nishimura M, Hsu JC. Reversal agents for direct oral anticoagulants: a focused review. Int J Cardiol 2016; 223: 244-250
  • 19 Icheva V, Nowak-Machen M, Budde U. , et al. Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case-series. J Thromb Haemost 2018; 16 (11) 2150-2158
  • 20 Mital A. Acquired von Willebrand syndrome. Adv Clin Exp Med 2016; 25 (06) 1337-1344
  • 21 Petricevic M. Knezevic J, Samoukovic G. , et al. Diagnosis and management of acquired von Willebrand disease in heart disease: a review of the literature. Thorac Cardiovasc Surg 2018; (e-pub ahead of print) DOI: 10.1055/s-0038-1673670.
  • 22 Lopes CT, Dos Santos TR, Brunori EH, Moorhead SA, Lopes Jde L, Barros AL. Excessive bleeding predictors after cardiac surgery in adults: integrative review. J Clin Nurs 2015; 24 (21-22): 3046-3062
  • 23 Hunt BJ, Parratt RN, Segal HC, Sheikh S, Kallis P, Yacoub M. Activation of coagulation and fibrinolysis during cardiothoracic operations. Ann Thorac Surg 1998; 65 (03) 712-718
  • 24 Mangano DT, Tudor IC, Dietzel C. ; Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354 (04) 353-365
  • 25 Myles PS, Smith JA, Forbes A. , et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 2017; 376 (02) 136-148
  • 26 Henry DA, Carless PA, Moxey AJ. , et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011; (03) CD001886
  • 27 Gerstein NS, Brierley JK, Windsor J. , et al. Antifibrinolytic agents in cardiac and noncardiac surgery: a comprehensive overview and update. J Cardiothorac Vasc Anesth 2017; 31 (06) 2183-2205
  • 28 Fergusson DA, Hébert PC, Mazer CD. , et al; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358 (22) 2319-2331
  • 29 Faraoni D, Rahe C, Cybulski KA. Use of antifibrinolytics in pediatric cardiac surgery: where are we now?. Paediatr Anaesth 2019; 29 (05) 435-440
  • 30 Faraoni D, Willems A, Melot C, De Hert S, Van der Linden P. Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg 2012; 42 (05) 781-786
  • 31 Lecker I, Wang D-S, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest 2012; 122 (12) 4654-4666
  • 32 Lu J, Meng H, Meng Z. , et al. Epsilon aminocaproic acid reduces blood transfusion and improves the coagulation test after pediatric open-heart surgery: a meta-analysis of 5 clinical trials. Int J Clin Exp Pathol 2015; 8 (07) 7978-7987
  • 33 Raghunathan K, Connelly NR, Kanter GJ. ε-Aminocaproic acid and clinical value in cardiac anesthesia. J Cardiothorac Vasc Anesth 2011; 25 (01) 16-19
  • 34 Bignami E, Cattaneo M, Crescenzi G. , et al. Desmopressin after cardiac surgery in bleeding patients. A multicenter randomized trial. Acta Anaesthesiol Scand 2016; 60 (07) 892-900
  • 35 Desborough MJ, Oakland K, Brierley C. , et al. Desmopressin use for minimising perioperative blood transfusion. Cochrane Database Syst Rev 2017; 7: CD001884
  • 36 Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis. Anaesthesia 2017; 72 (04) 519-531
  • 37 Bolliger D, Tanaka KA. Point-of-care coagulation testing in cardiac surgery. Semin Thromb Hemost 2017; 43 (04) 386-396
  • 38 Fleming K, Redfern RE, March RL. , et al. TEG-directed transfusion in complex cardiac surgery: impact on blood product usage. J Extra Corpor Technol 2017; 49 (04) 283-290
  • 39 Borgman MA, Spinella PC, Perkins JG. , et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007; 63 (04) 805-813
  • 40 Gunter Jr OL, Au BK, Isbell JM, Mowery NT, Young PP, Cotton BA. Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival. J Trauma 2008; 65 (03) 527-534
  • 41 Holcomb JB, Wade CE, Michalek JE. , et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg 2008; 248 (03) 447-458
  • 42 Mazzeffi MA, Chriss E, Davis K. , et al. Optimal plasma transfusion in patients undergoing cardiac operations with massive transfusion. Ann Thorac Surg 2017; 104 (01) 153-160
  • 43 Doussau A, Perez P, Puntous M. , et al; PLASMACARD Study Group. Fresh-frozen plasma transfusion did not reduce 30-day mortality in patients undergoing cardiopulmonary bypass cardiac surgery with excessive bleeding: the PLASMACARD multicenter cohort study. Transfusion 2014; 54 (04) 1114-1124
  • 44 Weisel JW, Litvinov RI. Fibrin formation, structure and properties. Subcell Biochem 2017; 82: 405-456
  • 45 Bilecen S, de Groot JA, Kalkman CJ. , et al. Effect of fibrinogen concentrate on intraoperative blood loss among patients with intraoperative bleeding during high-risk cardiac surgery: a randomized clinical trial. JAMA 2017; 317 (07) 738-747
  • 46 Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A. ; Surgical Clinical Outcome REsearch (SCORE) Group. Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc 2015; 4 (06) e002066
  • 47 Rahe-Meyer N, Solomon C, Hanke A. , et al. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology 2013; 118 (01) 40-50
  • 48 Rahe-Meyer N, Levy JH, Mazer CD. , et al. Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth 2016; 117 (01) 41-51
  • 49 Li J-Y, Gong J, Zhu F. , et al. Fibrinogen concentrate in cardiovascular surgery: a meta-analysis of randomized controlled trials. Anesth Analg 2018; 127 (03) 612-621
  • 50 Maeda T, Miyata S, Usui A. , et al. Safety of fibrinogen concentrate and cryoprecipitate in cardiovascular surgery: multicenter database study. J Cardiothorac Vasc Anesth 2019; 33 (02) 321-327
  • 51 Fitzgerald J, Lenihan M, Callum J. , et al. Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma. Br J Anaesth 2018; 120 (05) 928-934
  • 52 Chowdary P, Tang A, Watson D. , et al. Retrospective review of a prothrombin complex concentrate (Beriplex P/N) for the management of perioperative bleeding unrelated to oral anticoagulation. Clin Appl Thromb Hemost 2018; 24 (07) 1159-1169
  • 53 Cappabianca G, Mariscalco G, Biancari F. , et al. Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery. Crit Care 2016; 20: 5
  • 54 Arnékian V, Camous J, Fattal S, Rézaiguia-Delclaux S, Nottin R, Stéphan F. Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery. Interact Cardiovasc Thorac Surg 2012; 15 (03) 382-389
  • 55 Ortmann E, Besser MW, Sharples LD. , et al. An exploratory cohort study comparing prothrombin complex concentrate and fresh frozen plasma for the treatment of coagulopathy after complex cardiac surgery. Anesth Analg 2015; 121 (01) 26-33
  • 56 Balsam LB, Timek TA, Pelletier MP. Factor eight inhibitor bypassing activity (FEIBA) for refractory bleeding in cardiac surgery: review of clinical outcomes. J Card Surg 2008; 23 (06) 614-621
  • 57 Song HK, Tibayan FA, Kahl EA. , et al. Safety and efficacy of prothrombin complex concentrates for the treatment of coagulopathy after cardiac surgery. J Thorac Cardiovasc Surg 2014; 147 (03) 1036-1040
  • 58 Rao VK, Lobato RL, Bartlett B. , et al. Factor VIII inhibitor bypass activity and recombinant activated factor VII in cardiac surgery. J Cardiothorac Vasc Anesth 2014; 28 (05) 1221-1226
  • 59 Horstman DJ, van der Starre PJ. Detection of intracardiac thromboses after factor VIII inhibitor bypass activity administration by transesophageal echocardiography. J Cardiothorac Vasc Anesth 2007; 21 (04) 561-563
  • 60 Logan AC, Yank V, Stafford RS. Off-label use of recombinant factor VIIa in U.S. hospitals: analysis of hospital records. Ann Intern Med 2011; 154 (08) 516-522
  • 61 Karkouti K, Beattie WS, Wijeysundera DN. , et al. Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score-matched case-control analysis. Transfusion 2005; 45 (01) 26-34
  • 62 Diprose P, Herbertson MJ, O'Shaughnessy D, Gill RS. Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study. Br J Anaesth 2005; 95 (05) 596-602
  • 63 Gill R, Herbertson M, Vuylsteke A. , et al. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation 2009; 120 (01) 21-27
  • 64 Ekert H, Brizard C, Eyers R, Cochrane A, Henning R. Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy. Blood Coagul Fibrinolysis 2006; 17 (05) 389-395
  • 65 Habib AM, Calafiore AM, Cargoni M, Foschi M, Di Mauro M. Recombinant activated factor VII is associated with postoperative thromboembolic adverse events in bleeding after coronary surgery. Interact Cardiovasc Thorac Surg 2018; 27 (03) 350-356
  • 66 Downey L, Brown ML, Faraoni D, Zurakowski D, DiNardo JA. Recombinant factor VIIa is associated with increased thrombotic complications in pediatric cardiac surgery patients. Anesth Analg 2017; 124 (05) 1431-1436
  • 67 Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev 2012; (03) CD005011
  • 68 Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010; 363 (19) 1791-1800
  • 69 Berei TJ, Lillyblad MP, Wilson KJ, Garberich RF, Hryniewicz KM. Evaluation of systemic heparin versus bivalirudin in adult patients supported by extracorporeal membrane oxygenation. ASAIO J 2018; 64 (05) 623-629
  • 70 Hirsh J, Anand SS, Halperin JL, Fuster V. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 2001; 21 (07) 1094-1096
  • 71 Nawarskas JJ, Anderson JR. Bivalirudin: a new approach to anticoagulation. Heart Dis 2001; 3 (02) 131-137
  • 72 Hansen JB, Svensson B, Olsen R, Ezban M, Osterud B, Paulssen RH. Heparin induces synthesis and secretion of tissue factor pathway inhibitor from endothelial cells in vitro. Thromb Haemost 2000; 83 (06) 937-943
  • 73 Thomas J, Kostousov V, Teruya J. Bleeding and thrombotic complications in the use of extracorporeal membrane oxygenation. Semin Thromb Hemost 2018; 44 (01) 20-29
  • 74 Kalbhenn J, Schmidt R, Nakamura L, Schelling J, Rosenfelder S, Zieger B. Early diagnosis of acquired von Willebrand syndrome (AVWS) is elementary for clinical practice in patients treated with ECMO therapy. J Atheroscler Thromb 2015; 22 (03) 265-271
  • 75 Tauber H, Ott H, Streif W. , et al. Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers. Anesth Analg 2015; 120 (04) 730-736
  • 76 Linneweber J, Dohmen PM, Kertzscher U, Affeld K, Nosé Y, Konertz W. The effect of surface roughness on activation of the coagulation system and platelet adhesion in rotary blood pumps. Artif Organs 2007; 31 (05) 345-351
  • 77 Gorbet MB, Sefton MV. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials 2004; 25 (26) 5681-5703
  • 78 Doyle AJ, Hunt BJ. Current understanding of how extracorporeal membrane oxygenators activate haemostasis and other blood components. Front Med (Lausanne) 2018; 5: 352
  • 79 Passmore MR, Fung YL, Simonova G. , et al. Evidence of altered haemostasis in an ovine model of venovenous extracorporeal membrane oxygenation support. Crit Care 2017; 21 (01) 191
  • 80 Durila M, Smetak T, Hedvicak P, Berousek J. Extracorporeal membrane oxygenation-induced fibrinolysis detected by rotational thromboelastometry and treated by oxygenator exchange. Perfusion 2019; 34 (04) 330-333
  • 81 Levin EG, Marzec U, Anderson J, Harker LA. Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. J Clin Invest 1984; 74 (06) 1988-1995
  • 82 McVeen RV, Lorch V, Carroll RC. , et al. Changes in fibrinolytic factors in newborns during extracorporeal membrane oxygenation (ECMO). Am J Hematol 1991; 38 (03) 254-255
  • 83 Hundalani SG, Nguyen KT, Soundar E. , et al. Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation. Pediatr Crit Care Med 2014; 15 (05) e198-e205
  • 84 Kalbhenn J, Wittau N, Schmutz A, Zieger B, Schmidt R. Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy. Perfusion 2015; 30 (08) 675-682
  • 85 Biswas A, Ivaskevicius V, Thomas A, Oldenburg J. Coagulation factor XIII deficiency. Diagnosis, prevalence and management of inherited and acquired forms. Hamostaseologie 2014; 34 (02) 160-166
  • 86 Aubron C, DePuydt J, Belon F. , et al. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care 2016; 6 (01) 97
  • 87 Jackson HT, Longshore S, Feldman J, Zirschky K, Gingalewski CA, Gollin G. Chest tube placement in children during extracorporeal membrane oxygenation (ECMO). J Pediatr Surg 2014; 49 (01) 51-53 , discussion 53–54
  • 88 Huang P-M, Ko W-J, Tsai P-R. , et al. Aggressive management of massive hemothorax in patients on extracorporeal membrane oxygenation. Asian J Surg 2012; 35 (01) 16-22
  • 89 Rigby MR, Kamat P, Vats A, Heard M. Controlling intrathoracic hemorrhage on ECMO: help from factor VIIa and Virchow. Perfusion 2013; 28 (03) 201-206
  • 90 Abrams D, Agerstrand CL, Biscotti M, Burkart KM, Bacchetta M, Brodie D. Extracorporeal membrane oxygenation in the management of diffuse alveolar hemorrhage. ASAIO J 2015; 61 (02) 216-218
  • 91 Guo Z, Li X, Jiang L-Y, Xu L-F. Extracorporeal membrane oxygenation for the management of respiratory failure caused by diffuse alveolar hemorrhage. J Extra Corpor Technol 2009; 41 (01) 37-40
  • 92 Lee JH, Kim SW. Successful management of warfarin-exacerbated diffuse alveolar hemorrhage using an extracorporeal membrane oxygenation. Multidiscip Respir Med 2013; 8 (01) 16
  • 93 Wand O, Guber E, Guber A, Epstein Shochet G, Israeli-Shani L, Shitrit D. Inhaled tranexamic acid for hemoptysis treatment: a randomized controlled trial. Chest 2018; 154 (06) 1379-1384
  • 94 Segrelles Calvo G, De Granda-Orive I, López Padilla D. Inhaled tranexamic acid as an alternative for hemoptysis treatment. Chest 2016; 149 (02) 604
  • 95 Fletcher-Sandersjöö A, Thelin EP, Bartek Jr J. , et al. Incidence, outcome, and predictors of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation: a systematic and narrative review. Front Neurol 2018; 9: 548
  • 96 Fletcher-Sandersjöö A, Thelin EP, Bartek Jr J, Elmi-Terander A, Broman M, Bellander B-M. Management of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation (ECMO): an observational cohort study. PLoS One 2017; 12 (12) e0190365
  • 97 Muellenbach RM, Kredel M, Kunze E. , et al. Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. J Trauma Acute Care Surg 2012; 72 (05) 1444-1447
  • 98 Biderman P, Einav S, Fainblut M, Stein M, Singer P, Medalion B. Extracorporeal life support in patients with multiple injuries and severe respiratory failure: a single-center experience?. J Trauma Acute Care Surg 2013; 75 (05) 907-912
  • 99 Anton-Martin P, Braga B, Megison S, Journeycake J, Moreland J. Craniectomy and traumatic brain injury in children on extracorporeal membrane oxygenation support. Pediatr Emerg Care 2018; 34 (11) e204-e210
  • 100 Muensterer OJ, Laney D, Georgeson KE. Survival time of ECMO circuits on and off bleeding protocol: is there a higher risk of circuit clotting?. Eur J Pediatr Surg 2011; 21 (01) 30-32
  • 101 Downard CD, Betit P, Chang RW, Garza JJ, Arnold JH, Wilson JM. Impact of AMICAR on hemorrhagic complications of ECMO: a ten-year review. J Pediatr Surg 2003; 38 (08) 1212-1216
  • 102 Anselmi A, Guinet P, Ruggieri VG. , et al. Safety of recombinant factor VIIa in patients under extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 2016; 49 (01) 78-84