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Semin Thromb Hemost 2018; 44(01): 020-029
DOI: 10.1055/s-0037-1606179
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bleeding and Thrombotic Complications in the Use of Extracorporeal Membrane Oxygenation

James Thomas
1   Section of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Vadim Kostousov
2   Division of Transfusion Medicine & Coagulation, Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Jun Teruya
2   Division of Transfusion Medicine & Coagulation, Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
3   Departments of Medicine and Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
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Publikationsdatum:
12. September 2017 (online)

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Abstract

Extracorporeal membrane oxygenation (ECMO) has been used for >40 years to support lung and heart failure; however, bleeding and thrombosis remain serious complications. The known etiologies of bleeding include heparin effect or overdose, coagulopathy, thrombocytopenia, platelet dysfunction, acquired von Willebrand syndrome, and hyperfibrinolysis. Bleeding sites may include cannula insertion sites, recent surgical incisions, vascular access sites, lung, gastrointestinal tract, mouth, nose, thoracic cavity, abdominal cavity, and brain. Massive bleeding in the brain, the most feared bleeding complication, can be rapidly fatal because it occurs in a rigid closed space, is difficult to drain, and cannot be stopped with direct pressure to the bleeding site. Pulmonary hemorrhage may cause irreversible lung damage. Management should be swift and precise to prevent fatal bleeding. In contrast, etiologies of thrombosis include high fibrinogen and factor VIII levels, heparin resistance, and platelet activation. Achieving the optimal anticoagulation balance to prevent bleeding and thrombosis in ECMO patients is extremely complex. Experts in hemostasis should be a part of an institutional ECMO team and continuously available for immediate management.

Keywords

extracorporeal membrane oxygenation - ECMO - hyperfibrinolysis - heparin - hemolysis - acquired von Willebrand syndrome - bivalirudin
 

  • References

  • 1 Hill JD, O'Brien TG, Murray JJ. , et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972; 286 (12) 629-634
    CrossrefPubMedSuche in Google Scholar
  • 2 Bartlett RH, Gazzaniga AB, Jefferies MR, Huxtable RF, Haiduc NJ, Fong SW. Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy. Trans Am Soc Artif Intern Organs 1976; 22: 80-93
    PubMedSuche in Google Scholar
  • 3 MacLaren G, Combes A, Bartlett RH. Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. Intensive Care Med 2012; 38 (02) 210-220
    CrossrefPubMedSuche in Google Scholar
  • 4 Wang S, Palanzo D, Kunselman AR, Ündar A. In vitro hemodynamic evaluation of five 6 Fr and 8 Fr arterial cannulae in simulated neonatal cardiopulmonary bypass circuits. Artif Organs 2016; 40 (01) 56-64
    CrossrefPubMedSuche in Google Scholar
  • 5 Lequier L, Horton SB, McMullan DM, Bartlett RH. Extracorporeal membrane oxygenation circuitry. Pediatr Crit Care Med 2013; 14 (05) (Suppl. 01) S7-S12
    CrossrefPubMedSuche in Google Scholar
  • 6 Conrad SA, Rycus PT. Extracorporeal membrane oxygenation for refractory cardiac arrest. Ann Card Anaesth 2017; 20 (Supplement): S4-S10
    PubMedSuche in Google Scholar
  • 7 Sell LL, Cullen ML, Lerner GR, Whittlesey GC, Shanley CJ, Klein MD. Hypertension during extracorporeal membrane oxygenation: cause, effect, and management. Surgery 1987; 102 (04) 724-730
    PubMedSuche in Google Scholar
  • 8 O'Brien NF, Hall MW. Extracorporeal membrane oxygenation and cerebral blood flow velocity in children. Pediatr Crit Care Med 2013; 14 (03) e126-e134
    CrossrefPubMedSuche in Google Scholar
  • 9 Khaja WA, Bilen O, Lukner RB, Edwards R, Teruya J. Evaluation of heparin assay for coagulation management in newborns undergoing ECMO. Am J Clin Pathol 2010; 134 (06) 950-954
    CrossrefPubMedSuche in Google Scholar
  • 10 O'Meara LC, Alten JA, Goldberg KG. , et al. Anti-xa directed protocol for anticoagulation management in children supported with extracorporeal membrane oxygenation. ASAIO J 2015; 61 (03) 339-344
    CrossrefPubMedSuche in Google Scholar
  • 11 Yie K, Chon SH, Na CY. Activated clotting time test alone is inadequate to optimize therapeutic heparin dosage adjustment during post-cardiopulmonary resuscitational extracorporeal membrane oxygenation (e-CPR). Perfusion 2016; 31 (04) 307-315
    CrossrefPubMedSuche in Google Scholar
  • 12 Kostousov V, Nguyen K, Hundalani SG, Teruya J. The influence of free hemoglobin and bilirubin on heparin monitoring by activated partial thromboplastin time and anti-Xa assay. Arch Pathol Lab Med 2014; 138 (11) 1503-1506
    CrossrefPubMedSuche in Google Scholar
  • 13 Gehrie E, Laposata M. Test of the month: the chromogenic antifactor Xa assay. Am J Hematol 2012; 87 (02) 194-196
    CrossrefPubMedSuche in Google Scholar
  • 14 van Rossum AP, Vlasveld LT, van den Hoven LJ, de Wit CW, Castel A. False prolongation of the activated partial thromboplastin time (aPTT) in inflammatory patients: interference of C-reactive protein. Br J Haematol 2012; 157 (03) 394-395
    CrossrefPubMedSuche in Google Scholar
  • 15 Price EA, Jin J, Nguyen HM, Krishnan G, Bowen R, Zehnder JL. Discordant aPTT and anti-Xa values and outcomes in hospitalized patients treated with intravenous unfractionated heparin. Ann Pharmacother 2013; 47 (02) 151-158
    CrossrefPubMedSuche in Google Scholar
  • 16 Hensch L, Kostousov V, Bruzdoski K. , et al. Can rotational thromboelastometry predict bleeding risk in patients with lupus anticoagulant?. Int Jnl Lab Hem 2016; 38 (Suppl. 02) 46
    PubMedSuche in Google Scholar
  • 17 Schmidt DE, Majeed A, Bruzelius M, Odeberg J, Holmström M, Ågren A. A prospective diagnostic accuracy study evaluating rotational thromboelastometry and thromboelastography in 100 patients with von Willebrand disease. Haemophilia 2017; 23 (02) 309-318
    CrossrefPubMedSuche in Google Scholar
  • 18 Brodin E, Svensson B, Paulssen RH, Nordoy A, Hansen JB. Intravascular release and urinary excretion of tissue factor pathway inhibitor during heparin treatment. J Lab Clin Med 2004; 144 (05) 246-253 , discussion 226–227
    CrossrefPubMedSuche in Google Scholar
  • 19 Winckers K, ten Cate H, Hackeng TM. The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis. Blood Rev 2013; 27 (03) 119-132
    CrossrefPubMedSuche in Google Scholar
  • 20 Ariëns RA, Alberio G, Moia M, Mannucci PM. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis. Thromb Haemost 1999; 81 (02) 203-207
    Thieme ConnectPubMedSuche in Google Scholar
  • 21 Vincent LM, Tran S, Livaja R, Bensend TA, Milewicz DM, Dahlbäck B. Coagulation factor V(A2440G) causes east Texas bleeding disorder via TFPIα. J Clin Invest 2013; 123 (09) 3777-3787
    CrossrefPubMedSuche in Google Scholar
  • 22 Cunha ML, Bakhtiari K, Peter J, Marquart JA, Meijers JC, Middeldorp S. A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function. Blood 2015; 125 (11) 1822-1825
    CrossrefPubMedSuche in Google Scholar
  • 23 Newall F, Johnston L, Summerhayes R. , et al. Novel interactions between UFH and TFPI in children. Br J Haematol 2010; 151 (04) 376-380
    CrossrefPubMedSuche in Google Scholar
  • 24 Buck ML. Bivalirudin as an alternative to heparin for anticoagulation in infants and children. J Pediatr Pharmacol Ther 2015; 20 (06) 408-417
    PubMedSuche in Google Scholar
  • 25 McNair E, Marcoux JA, Bally C, Gamble J, Thomson D. Bivalirudin as an adjunctive anticoagulant to heparin in the treatment of heparin resistance during cardiopulmonary bypass-assisted cardiac surgery. Perfusion 2016; 31 (03) 189-199
    CrossrefPubMedSuche in Google Scholar
  • 26 Cardinale M, Ha M, Liu MH, Reardon DP. Direct thrombin inhibitor resistance and possible mechanisms. Hosp Pharm 2016; 51 (11) 922-927
    CrossrefPubMedSuche in Google Scholar
  • 27 Nagle EL, Dager WE, Duby JJ. , et al. Bivalirudin in pediatric patients maintained on extracorporeal life support. Pediatr Crit Care Med 2013; 14 (04) e182-e188
    CrossrefPubMedSuche in Google Scholar
  • 28 Pieri M, Agracheva N, Bonaveglio E. , et al. Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study. J Cardiothorac Vasc Anesth 2013; 27 (01) 30-34
    CrossrefPubMedSuche in Google Scholar
  • 29 Robson R, White H, Aylward P, Frampton C. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther 2002; 71 (06) 433-439
    CrossrefPubMedSuche in Google Scholar
  • 30 Young G, Tarantino MD, Wohrley J, Weber LC, Belvedere M, Nugent DJ. Pilot dose-finding and safety study of bivalirudin in infants <6 months of age with thrombosis. J Thromb Haemost 2007; 5 (08) 1654-1659
    CrossrefPubMedSuche in Google Scholar
  • 31 Young G, Yonekawa KE, Nakagawa PA, Blain RC, Lovejoy AE, Nugent DJ. Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography. Blood Coagul Fibrinolysis 2007; 18 (06) 547-553
    CrossrefPubMedSuche in Google Scholar
  • 32 Stratmann G, deSilva AM, Tseng EE. , et al. Reversal of direct thrombin inhibition after cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia. Anesth Analg 2004; 98 (06) 1635-1639
    PubMedSuche in Google Scholar
  • 33 Gosselin RC, King JH, Janatpur KA, Dager WH, Larkin EC, Owings JT. Effects of pentasaccharide (fondaparinux) and direct thrombin inhibitors on coagulation testing. Arch Pathol Lab Med 2004; 128 (10) 1142-1145
    Suche in Google Scholar
  • 34 Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost 2007; 98 (01) 234-242
    Thieme ConnectPubMedSuche in Google Scholar
  • 35 Curvers J, van de Kerkhof D, Stroobants AK, van den Dool EJ, Scharnhorst V. Measuring direct thrombin inhibitors with routine and dedicated coagulation assays: which assay is helpful?. Am J Clin Pathol 2012; 138 (04) 551-558
    CrossrefPubMedSuche in Google Scholar
  • 36 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
    CrossrefPubMedSuche in Google Scholar
  • 37 Ranucci M, Baryshnikova E, Cotza M. , et al; Group for the Surgical and Clinical Outcome Research (SCORE). Coagulation monitoring in postcardiotomy ECMO: conventional tests, point-of-care, or both?. Minerva Anestesiol 2016; 82 (08) 858-866
    PubMedSuche in Google Scholar
  • 38 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
    CrossrefPubMedSuche in Google Scholar
  • 39 Robinson TM, Kickler TS, Walker LK, Ness P, Bell W. Effect of extracorporeal membrane oxygenation on platelets in newborns. Crit Care Med 1993; 21 (07) 1029-1034
    CrossrefPubMedSuche in Google Scholar
  • 40 Lukito P, Wong A, Jing J. , et al. Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI. J Thromb Haemost 2016; 14 (11) 2253-2260
    CrossrefPubMedSuche in Google Scholar
  • 41 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
    CrossrefPubMedSuche in Google Scholar
  • 42 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
    CrossrefPubMedSuche in Google Scholar
  • 43 Heilmann C, Geisen U, Beyersdorf F. , et al. Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 2012; 38 (01) 62-68
    CrossrefPubMedSuche in Google Scholar
  • 44 Jones MB, Ramakrishnan K, Alfares FA. , et al. Acquired von Willebrand syndrome: an under-recognized cause of major bleeding in the cardiac intensive care unit. World J Pediatr Congenit Heart Surg 2016; 7 (06) 711-716
    CrossrefPubMedSuche in Google Scholar
  • 45 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
    CrossrefPubMedSuche in Google Scholar
  • 46 Pasala S, Fiser RT, Stine KC, Swearingen CJ, Prodhan P. von Willebrand factor multimers in pediatric extracorporeal membrane oxygenation support. ASAIO J 2014; 60 (04) 419-423
    CrossrefPubMedSuche in Google Scholar
  • 47 Teruya J, Burgman C. Bleeding associated with ECMO. In: Teruya J. ed. Management of Bleeding Patients, 1st ed. Springer; 2016: 249-254
    Suche in Google Scholar
  • 48 Tiede A, Priesack J, Werwitzke S. , et al. Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single-centre cohort study. J Thromb Haemost 2008; 6 (04) 569-576
    CrossrefPubMedSuche in Google Scholar
  • 49 Hudzik B, Kaczmarski J, Pacholewicz J, Zakliczynski M, Gasior M, Zembala M. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis. Kardiochir Torakochirurgia Pol 2015; 12 (03) 233-237
    PubMedSuche in Google Scholar
  • 50 Da Q, Teruya M, Guchhait P, Teruya J, Olson JS, Cruz MA. Free hemoglobin increases von Willebrand factor-mediated platelet adhesion in vitro: implications for circulatory devices. Blood 2015; 126 (20) 2338-2341
    CrossrefPubMedSuche in Google Scholar
  • 51 Sulkowski JP, Cooper JN, Pearson EG. , et al. Hemolysis-associated nitric oxide dysregulation during extracorporeal membrane oxygenation. J Extra Corpor Technol 2014; 46 (03) 217-223
    PubMedSuche in Google Scholar
  • 52 Zhou Z, Han H, Cruz MA, López JA, Dong JF, Guchhait P. Haemoglobin blocks von Willebrand factor proteolysis by ADAMTS-13: a mechanism associated with sickle cell disease. Thromb Haemost 2009; 101 (06) 1070-1077
    Thieme ConnectPubMedSuche in Google Scholar
  • 53 Pan KC, McKenzie DP, Pellegrino V, Murphy D, Butt W. The meaning of a high plasma free haemoglobin: retrospective review of the prevalence of haemolysis and circuit thrombosis in an adult ECMO centre over 5 years. Perfusion 2016; 31 (03) 223-231
    CrossrefPubMedSuche in Google Scholar
  • 54 Omar HR, Mirsaeidi M, Socias S. , et al. Plasma free hemoglobin is an independent predictor of mortality among patients on extracorporeal membrane oxygenation support. PLoS One 2015; 10 (04) e0124034
    CrossrefPubMedSuche in Google Scholar
  • 55 Bembea MM, Annich G, Rycus P, Oldenburg G, Berkowitz I, Pronovost P. Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey. Pediatr Crit Care Med 2013; 14 (02) e77-e84
    CrossrefPubMedSuche in Google Scholar
  • 56 Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med 2005; 353 (10) 1028-1040
    CrossrefPubMedSuche in Google Scholar