Top

Published in:

01-04-2015

Management of anticoagulation and antiplatelet therapy in patients with left ventricular assist devices

Author: Lisa M. Baumann Kreuziger

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2015

Abstract

Left ventricular assist devices (LVADs) have increased the survival of patients with advanced heart failure fourfold. Despite these advances, significant bleeding and thrombotic complications occur. Hemorrhage requiring surgery has been reported in up to 30 % of adults and 50 % of children after LVAD placement. LVAD thrombosis and embolic stroke lead to significant long-term morbidity. Adults are treated with antithrombotic therapy to prevent thrombotic complications, but the amount and intensity of treatment differs between institutions. The goal international normalized ratio for warfarin therapy varies from 1.5 to 3.0. Some physicians manage adult LVAD patients without antiplatelet medication, whereas other adults are treated with aspirin as a single agent or combined with dipyridamole. In contrast, physicians typically manage children with LVADs using the Edmonton Anticoagulation and Platelet Inhibition Protocol, a detailed algorithm for anticoagulation and antiplatelet treatment modified based on thromboelastography results. LVAD implantation causes consumption of coagulation proteins, activation of fibrinolysis, and loss of high molecular weight von Willebrand protein multimers. How these changes in the coagulation system influence the risk of hemorrhage and initiation of thrombosis is unknown. Prospective, controlled studies are needed to determine the antithrombotic regimen that most effectively balances bleeding and thrombosis in LVAD patients.

Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J (2010) Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121:e46–e215. doi:10.1161/CIRCULATIONAHA.109.192667 CrossRefPubMed

Heron M (2013) Deaths: leading causes for 2010. Natl Vital Stat Rep 62:1–96PubMed

Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Goldfarb SB, Levvey BJ, Meiser B, Yusen RD, Stehlik J (2014) The registry of the International Society for Heart and Lung Transplantation: thirty-first official adult heart transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant 33:996–1008. doi:10.1016/j.healun.2014.08.003 CrossRefPubMed

Network OPaT (2014) United States Department of Health and Human Services. http://optn.transplant.hrsa.gov/converge/latestdata/rptData.asp. Accessed 12 Nov 2014

Martin J, Friesewinkel O, Benk C, Sorg S, Schultz S, Beyersdorf F (2006) Improved durability of the HeartMate XVE left ventricular assist device provides safe mechanical support up to 1 year but is associated with high risk of device failure in the second year. J Heart Lung Transplant 25:384–390. doi:10.1016/j.healun.2005.11.437 CrossRefPubMed

Almond CS, Morales DL, Blackstone EH, Turrentine MW, Imamura M, Massicotte MP, Jordan LC, Devaney EJ, Ravishankar C, Kanter KR, Holman W, Kroslowitz R, Tjossem C, Thuita L, Cohen GA, Buchholz H, St Louis JD, Nguyen K, Niebler RA, Walters HL 3rd, Reemtsen B, Wearden PD, Reinhartz O, Guleserian KJ, Mitchell MB, Bleiweis, Canter CE, Humpl T (2013) Berlin heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation 127:1702–1711. doi:10.1161/CIRCULATIONAHA.112.000685 CrossRefPubMed

Birschmann I, Dittrich M, Eller T, Wiegmann B, Reininger AJ, Budde U, Struber M (2014) Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices. J Heart Lung Transplant 33:80–87. doi:10.1016/j.healun.2013.11.010 CrossRefPubMed

Himmelreich G, Ullmann H, Riess H, Rosch R, Loebe M, Schiessler A, Hetzer R (1995) Pathophysiologic role of contact activation in bleeding followed by thromboembolic complications after implantation of a ventricular assist device. ASAIO J 41:M790–M794CrossRefPubMed

Slaughter, Sobieski MA, Gallagher C, Graham J, Brandise J, Stein R (2008) Fibrinolytic activation during long-term support with the HeartMate II left ventricular assist device. ASAIO J 54:115–119. doi:10.1097/MAT.0b013e318161a987 CrossRefPubMed

10.

John R, Panch S, Hrabe J, Wei P, Solovey A, Joyce L, Hebbel R (2009) Activation of endothelial and coagulation systems in left ventricular assist device recipients. Ann Thorac Surg 88:1171–1179. doi:10.1016/j.athoracsur.2009.06.095 CrossRefPubMed

11.

Slaughter MS, Sobieski MA, Graham JD, Pappas PS, Tatooles AJ, Koenig SC (2011) Platelet activation in heart failure patients supported by the HeartMate II ventricular assist device. Int J Artif Organs 34:461–468. doi:10.5301/ijao.2011.8459 CrossRefPubMed

12.

Matsubayashi H, Fastenau DR, McIntyre JA (2000) Changes in platelet activation associated with left ventricular assist system placement. J Heart Lung Transplant 19:462–468CrossRefPubMed

13.

Sheriff J, Girdhar G, Chiu WC, Jesty J, Slepian MJ, Bluestein D (2014) Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device. J Thromb Thrombolysis 37:499–506. doi:10.1007/s11239-013-0997-6 CrossRefPubMedCentralPubMed

14.

Klovaite J, Gustafsson F, Mortensen SA, Sander K, Nielsen LB (2009) Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). J Am Coll Cardiol 53:2162–2167. doi:10.1016/j.jacc.2009.02.048 CrossRefPubMed

15.

Meyer AL, Malehsa D, Budde U, Bara C, Haverich A, Strueber M (2014) Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist device. JACC Heart Fail 2:141–145. doi:10.1016/j.jchf.2013.10.008 CrossRefPubMed

16.

Muthiah K, Robson D, Macdonald PS, Keogh AM, Kotlyar E, Granger E, Dhital K, Spratt P, Hayward CS (2013) Increased incidence of angiodysplasia of the gastrointestinal tract and bleeding in patients with continuous flow left ventricular assist devices (LVADs). Int J Artif Organs 36:449–454. doi:10.5301/ijao.5000224 CrossRefPubMed

17.

Demirozu ZT, Radovancevic R, Hochman LF, Gregoric ID, Letsou GV, Kar B, Bogaev RC, Frazier OH (2011) Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device. J Heart Lung Transplant 30:849–853. doi:10.1016/j.healun.2011.03.008 PubMed

18.

Crow S, Chen D, Milano C, Thomas W, Joyce L, Piacentino V 3rd, Sharma R, Wu J, Arepally G, Bowles D, Rogers J, Villamizar-Ortiz N (2010) Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. Ann Thorac Surg 90:1263–1269. doi:10.1016/j.athoracsur.2010.04.099 (discussion 9)CrossRefPubMed

19.

Cushing M, Kawaguchi K, Friedman KD, Mark T (2012) Factor VIII/von Willebrand factor concentrate therapy for ventricular assist device-associated acquired von Willebrand disease. Transfusion 52:1535–1541. doi:10.1111/j.1537-2995.2011.03500.x CrossRefPubMed

20.

Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, Sun B, Tatooles AJ, Delgado RM 3rd, Long JW, Wozniak TC, Ghumman W, Farrar DJ, Frazier OH (2009) Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 361:2241–2251. doi:10.1056/NEJMoa0909938 CrossRefPubMed

21.

Aaronson KD, Slaughter MS, Miller LW, McGee EC, Cotts WG, Acker MA, Jessup ML, Gregoric ID, Loyalka P, Frazier OH, Jeevanandam V, Anderson AS, Kormos RL, Teuteberg JJ, Levy WC, Naftel DC, Bittman RM, Pagani FD, Hathaway DR, Boyce SW (2012) Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation 125:3191–3200. doi:10.1161/CIRCULATIONAHA.111.058412 CrossRefPubMed

22.

Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, Conte JV, Naka Y, Mancini D, Delgado RM, MacGillivray TE, Farrar DJ, Frazier OH (2007) Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 357:885–896. doi:10.1056/NEJMoa067758 CrossRefPubMed

23.

Starling RC, Moazami N, Silvestry SC, Ewald G, Rogers JG, Milano CA, Rame JE, Acker MA, Blackstone EH, Ehrlinger J, Thuita L, Mountis MM, Soltesz EG, Lytle BW, Smedira NG (2014) Unexpected abrupt increase in left ventricular assist device thrombosis. N Engl J Med 370:33–40. doi:10.1056/NEJMoa1313385 CrossRefPubMed

24.

Fraser CD Jr, Jaquiss RD, Rosenthal DN, Humpl T, Canter CE, Blackstone EH, Naftel DC, Ichord RN, Bomgaars L, Tweddell JS, Massicotte MP, Turrentine MW, Cohen GA, Devaney EJ, Pearce FB, Carberry KE, Kroslowitz R, Almond CS (2012) Prospective trial of a pediatric ventricular assist device. N Engl J Med 367:532–541. doi:10.1056/NEJMoa1014164 CrossRefPubMed

25.

Feldman D, Pamboukian SV, Teuteberg JJ, Birks E, Lietz K, Moore SA, Morgan JA, Arabia F, Bauman ME, Buchholz HW, Deng M, Dickstein ML, El-Banayosy A, Elliot T, Goldstein DJ, Grady KL, Jones K, Hryniewicz K, John R, Kaan A, Kusne S, Loebe M, Massicotte MP, Moazami N, Mohacsi P, Mooney M, Nelson T, Pagani F, Perry W, Potapov EV, Rame JE, Russell SD, Sorensen EN, Sun B, Strueber M, Mangi AA, Petty MG, Rogers J (2013) The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant 32:157–187. doi:10.1016/j.healun.2012.09.013 CrossRefPubMed

26.

Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, Miller MA, Baldwin JT, Young JB (2014) Sixth INTERMACS annual report: a 10,000-patient database. J Heart Lung Transplant 33:555–564. doi:10.1016/j.healun.2014.04.010 CrossRefPubMed

27.

Galeone A, Rotunno C, Guida P, Bisceglie A, Rubino G, Schinosa LDL, Paparella D (2013) Monitoring incomplete heparin reversal and heparin rebound after cardiac surgery. J Cardiothorac Vasc Anesth 27:853–858. doi:10.1053/j.jvca.2012.10.020 CrossRefPubMed

28.

Slaughter MS, Naka Y, John R, Boyle A, Conte JV, Russell SD, Aaronson KD, Sundareswaran KS, Farrar DJ, Pagani FD (2010) Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant 29:616–624. doi:10.1016/j.healun.2010.02.003 CrossRefPubMed

29.

Terrovitis J, Kapelios C, Vakrou S, Diakos N, Katsaros L, Ntalianis A, Kaldara E, Kontoyannis D, Charitos C, Nanas J (2011) Comparison of the effectiveness and safety of dabigatran etexilate versus acenocoumarol in patients with left ventricular assist device. Am Heart Assoc 2011 Annl Meet 124(Suppl. 21):A14809

30.

Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369:1206–1214. doi:10.1056/NEJMoa1300615 CrossRefPubMed

31.

Bunte MC, Blackstone EH, Thuita L, Fowler J, Joseph L, Ozaki A, Starling RC, Smedira NG, Mountis MM (2013) Major bleeding during HeartMate II support. J Am Coll Cardiol 62:2188–2196. doi:10.1016/j.jacc.2013.05.089 CrossRefPubMed

32.

Stern DR, Kazam J, Edwards P, Maybaum S, Bello RA, D’Alessandro DA, Goldstein DJ (2010) Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Cardiothorac Surg 25:352–356. doi:10.1111/j.1540-8191.2010.01025.x CrossRef

33.

Whitson BA, Eckman P, Kamdar F, Lacey A, Shumway SJ, Liao KK, John R (2014) Hemolysis, pump thrombus, and neurologic events in continuous-flow left ventricular assist device recipients. Ann Thorac Surg 97:2097–2103. doi:10.1016/j.athoracsur.2014.02.041 CrossRefPubMed

34.

Jennings DL, Brewer R, Williams C (2012) Impact of continuous flow left ventricular assist device on the pharmacodynamic response to warfarin early after implantation. Ann Pharmacother 46:1266–1267. doi:10.1345/aph.1R266 CrossRefPubMed

35.

Jennings D, McDonnell J, Schillig J (2011) Assessment of long-term anticoagulation in patients with a continuous-flow left-ventricular assist device: a pilot study. J Thorac Cardiovasc Surg 142:e1–e2. doi:10.1016/j.jtcvs.2011.03.029 CrossRefPubMed

36.

Bishop MA, Streiff MB, Ensor CR, Tedford RJ, Russell SD, Ross PA (2014) Pharmacist-managed international normalized ratio patient self-testing is associated with increased time in therapeutic range in patients with left ventricular assist devices at an Academic Medical Center. ASAIO J 60:193–198. doi:10.1097/mat.0000000000000047 CrossRefPubMed

37.

Litzler PY, Smail H, Barbay V, Nafeh-Bizet C, Bouchart F, Baste JM, Abriou C, Bessou JP (2014) Is anti-platelet therapy needed in continuous flow left ventricular assist device patients? A single-centre experience. Eur J Cardiothorac Surg 45:55–59. doi:10.1093/ejcts/ezt228 (discussion 9-60)CrossRefPubMed

38.

Slaughter, Pagani FD, McGee EC, Birks EJ, Cotts WG, Gregoric I, Frazier OH, Icenogle T, Najjar SS, Boyce SW, Acker MA, John R, Hathaway, Najarian KB, Aaronson KD (2013) HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant 32:675–683. doi:10.1016/j.healun.2013.04.004 CrossRefPubMed

39.

Backes D, van den Bergh WM, van Duijn AL, Lahpor JR, van Dijk D, Slooter AJ (2012) Cerebrovascular complications of left ventricular assist devices. Eur J Cardiothorac Surg 42:612–620. doi:10.1093/ejcts/ezs320 CrossRefPubMed

40.

Karimi A, Beaver TM, Hess PJ, Martin TD, Staples ED, Schofield RS, Hill JA, Aranda JM, Klodell CT (2014) Close antiplatelet therapy monitoring and adjustment based upon thrombelastography may reduce late-onset bleeding in HeartMate II ecipients. Interact CardioVasc Thorac Surg 18:457–465. doi:10.1093/icvts/ivt546 CrossRefPubMed

41.

Almond CS, Buchholz H, Massicotte P, Ichord R, Rosenthal DN, Uzark K, Jaquiss RD, Kroslowitz R, Kepler MB, Lobbestael A, Bellinger D, Blume ED, Fraser CD Jr, Bartlett RH, Thiagarajan R, Jenkins K (2011) Berlin heart EXCOR pediatric ventricular assist device investigational device exemption study: study design and rationale. Am Heart J 162:425–435. doi:10.1016/j.ahj.2011.05.026 (e6)CrossRefPubMed

42.

Bauman ME, Black K, Kuhle S, Wang L, Legge L, Callen-Wicks D, Mitchell L, Bajzar L, Massicotte MP (2009) KIDCLOT: the importance of validated educational intervention for optimal long term warfarin management in children. Thromb Res 123:707–709. doi:10.1016/j.thromres.2008.07.012 CrossRefPubMed

43.

Jennings DL, Jacob M, Chopra A, Nemerovski CW, Morgan JA, Lanfear DE (2014) Safety of anticoagulation reversal in patients supported with continuous-flow left-ventricular assist devices. ASAIO J. 10.1097/MAT.0000000000000077

44.

Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN (2013) Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 128:1234–1243. doi:10.1161/CIRCULATIONAHA.113.002283 PubMed

45.

Eckman PM, John R (2012) Bleeding and thrombosis in patients with continuous-flow ventricular assist devices. Circulation 125:3038–3047. doi:10.1161/circulationaha.111.040246 CrossRefPubMed

46.

Loyaga-Rendon RY, Taimoor H, Tallaj JA, Acharya D, Holman W, Kirklin J, Pamboukian SV (2014) Octreotide in the mangement of recurrent gastrointestinal bleed in patients supported by continuous flow left ventricular assist devices. ASAIO J. 10.1097/MAT.0000000000000143

47.

Wilson TJ, Stetler WR Jr, Al-Holou WN, Sullivan SE, Fletcher JJ (2013) Management of intracranial hemorrhage in patients with left ventricular assist devices. J Neurosurg 118:1063–1068. doi:10.3171/2013.1.jns121849 CrossRefPubMed

48.

Goldstein DJ, John R, Salerno C, Silvestry S, Moazami N, Horstmanshof D, Adamson R, Boyle A, Zucker M, Rogers J, Russell S, Long J, Pagani F, Jorde U (2013) Algorithm for the diagnosis and management of suspected pump thrombus. J Heart Lung Transplant 32:667–670. doi:10.1016/j.healun.2013.05.002 CrossRefPubMed

49.

Ballew CC, Benton EM, Groves DS, Kennedy JLW, Ailawaid G, Kern JA, Bergin JD (2013) Comparing survival of HMII patients with elevated LDH: implications for medical and surgical management. J Heart Lung Transplant 32:S38CrossRef

50.

Jennings DL, Weeks PA (2014) Thrombosis in continuous-flow left ventricular assist devices: pathophysiology, prevention, and pharmacologic management. Pharmacotherapy. doi:10.1002/phar.1501 PubMed

Title: Management of anticoagulation and antiplatelet therapy in patients with left ventricular assist devices
Author: Lisa M. Baumann Kreuziger
Publication date: 01-04-2015
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 3/2015
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-014-1162-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2015

Engaging with quality improvement in anticoagulation management

Proceedings of the 13th National Conference on Anticoagulant Therapy

New approaches to managing nonvalvular atrial fibrillation: what are the thromboembolic implications?

Clinical significance and management of subsegmental pulmonary embolism

Proceedings of the 13th National Conference on Anticoagulant Therapy

Current antiplatelet agents: place in therapy and role of genetic testing

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials