Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO.
Methods:
Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016.
Results:
The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study).
Conclusion:
Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.
CombesABrodieDBartlettR; International ECMO Network (ECMONet). Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med. 2014;190(5):488–496.
2.
AsmussenSMaybauerDMFraserJF. Extracorporeal membrane oxygenation in burn and smoke inhalation injury. Burns. 2013;39(3):429–435.
3.
PeekGJClemensFElbourneD. CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC Health Serv Res. 2006;6:163.
4.
AilawadiGZacourRK. Cardiopulmonary bypass/extracorporeal membrane oxygenation/left heart bypass: indications, techniques, and complications. Surg Clin North Am. 2009;89(4):781–796, vii–viii.
5.
CohenM. Heparin-induced thrombocytopenia and the clinical use of low molecular weight heparins in acute coronary syndromes. Semin Hematol. 1999;36(1 suppl 1):33–36.
6.
WarkentinTE. Fondaparinux: does it cause HIT? Can it treat HIT?Expert Rev Hematol. 2010;3(5):567–581.
7.
JyotiAMaheshwariADanielEMotiharABhathiwalRSSharmaD. Bivalirudin in venovenous extracorporeal membrane oxygenation. J Extra Corpor Technol. 2014;46(1):94–97.
8.
GreinacherA. Clinical Practice. Heparin-induced thrombocytopenia. N Engl J Med. 2015;373(3):252–261.
9.
WarkentinTESheppardJA. Testing for heparin-induced thrombocytopenia antibodies. Transfus Med Rev. 2006;20(4):259–272.
10.
LeeGMArepallyGM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2013;2013:668–674.
11.
MartelNLeeJWellsPS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710–2715.
12.
KosterAWengYBöttcherWGromannTKuppeHHetzerR. Successful use of bivalirudin as anticoagulant for ECMO in a patient with acute HIT. Ann Thorac Surg. 2007;83(5):1865–1867.
13.
WarkentinTEGreinacherAKosterA. Heparin-induced thrombocytopenia in patients with ventricular assist devices: are new prevention strategies required?Ann Thorac Surg. 2009;87(5):1633–1640.
14.
BeattieGWJeffreyRR. Is there evidence that fresh frozen plasma is superior to antithrombin administration to treat heparin resistance in cardiac surgery?Interact Cardiovasc Thorac Surg. 2014;18(1):117–120.
AouifiABlancPPiriouV. Cardiac surgery with cardiopulmonary bypass in patients with type II heparin-induced thrombocytopenia. Ann Thorac Surg. 2001;71(2):678–683.
17.
KosterADykeCMAldeaG. Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: results of the CHOOSE-ON trial. Ann Thorac Surg. 2007;83(2):572–577.
18.
DykeCMSmediraNGKosterA. A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study. J Thorac Cardiovasc Surg. 2006;131(3):533–539.
19.
StoneGWMcLaurinBTCoxDA; ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355(21):2203–2216.
20.
StoneGWWitzenbichlerBGuagliumiG; HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358(21):2218–2230.
21.
KushnerFGHandMSmithSCJr. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54(23):2205–2241.
22.
ValgimigliMFrigoliELeonardiS; MATRIX Investigators. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med. 2015;373(11):997–1009.
23.
LiberatiAAltmanDGTetzlaffJ. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–e34.
24.
SellRLPatelKCraneT. Bivalirudin use in heparin resistance patient for extracorporeal membrane oxygenation: a review and case study. J Extra Corpor Technol. 2009;41/1(a17).
25.
PieriMAgrachevaNBonaveglioE. Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study. J Cardiothorac Vasc Anesth. 2013;27(1):30–34.
26.
RanucciMBallottaAKandilH; Surgical and Clinical Outcome Research Group. Bivalirudin-based versus conventional heparin anticoagulation for postcardiotomy extracorporeal membrane oxygenation. Crit Care. 2011;15(6):r275.
27.
NagleELDagerWEDubyJJ. Bivalirudin in pediatric patients maintained on extracorporeal life support. Pediatr Crit Care Med. 2013;14(4):e182–e188.
28.
PollakUYacobobichJTamaryHDaganOManor-ShulmanO. Heparin-induced thrombocytopenia and extracorporeal membrane oxygenation: a case report and review of the literature. J Extra Corpor Technol. 2011;43(1):5–12.
29.
PappalardoFMajGScandroglioASampietroFZangrilloAKosterA. Bioline heparin-coated ECMO with bivalirudin anticoagulation in a patient with acute heparin-induced thrombocytopenia: the immune reaction appeared to continue unabated. Perfusion. 2009;24(2):135–137.
30.
PrestonTJDaltonHJNicolKKFerrallBRMillerJCHayesDJr. Plasma exchange on venovenous extracorporeal membrane oxygenation with bivalirudin anticoagulation. World J Pediatr Congenit Heart Surg. 2015;6(1):119–122.
31.
RanucciM. Bivalirudin and post-cardiotomy ECMO: a word of caution. Crit Care. 2012;16(3):427.
32.
RobsonRWhiteHAylwardPFramptonC. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther. 2002;71(6):433–439.
33.
TsuLVDagerWE. Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia. Ann Pharmacother. 2011;45(10):1185–1192.
LinkinsLADansALMooresLK; American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e495s–e530s.
37.
MorshuisMBoergermannJGummertJKosterA. A modified technique for implantation of the HeartWare left ventricular assist device when using bivalirudin anticoagulation in patients with acute heparin-induced thrombocytopenia. Interact Cardiovasc Thorac Surg. 2013;17(2):225–226.
KosterABuzSKrabatschTYeterRHetzerR. Bivalirudin anticoagulation during cardiac surgery: a single-center experience in 141 patients. Perfusion. 2009;24(1):7–11.
NagleELTsuLVDagerWE. Bivalirudin for anticoagulation during hypothermic cardiopulmonary bypass and recombinant factor VIIa for iatrogenic coagulopathy. Ann Pharmacother. 2011;45(9):e47.
43.
VavraKALutzMFSmytheMA. Recombinant factor VIIa to manage major bleeding from newer parenteral anticoagulants. Ann Pharmacother. 2010;44(4):718–726.
44.
RepesseXAuSMBrechotN. Recombinant factor VIIa for uncontrollable bleeding in patients with extracorporeal membrane oxygenation: report on 15 cases and literature review. Crit Care. 2013;17(2):r55.
45.
BauerCVichovaZFfrenchP. Extracorporeal membrane oxygenation with danaparoid sodium after massive pulmonary embolism. Anesth Analg. 2008;106(4):1101–1103.
46.
ParlarAISayarUCevirmeDYurukMAMataraciI. Successful use of fondaparinux in a patient with heparin-induced thrombocytopenia while on extracorporeal membrane oxygenation after mitral valve redo surgery. Int J Artif Organs. 2014;37(4):344–347.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
