Advertisement

Thrombosis and Modern Anticoagulation Options for the Adult with Congenital Heart Disease

  • Therese M. GigliaEmail author
  • Char M. Witmer
  • Yuli Y. Kim
Chapter
Part of the Congenital Heart Disease in Adolescents and Adults book series (CHDAA)

Abstract

The anatomy and physiology of adults with congenital heart disease place them at increased risk for thrombosis. This chapter discusses the most common thromboses, namely, deep venous thrombosis, pulmonary embolism, arrhythmias and thromboembolic stroke, thrombosis associated with prosthetic valves, and special concerns of the adult with Fontan circulation. The chapter closes with a discussion of therapeutics for thrombosis prevention and management.

Keywords

Adult with congenital heart disease Anticoagulation Thrombosis Deep venous thrombosis Pulmonary embolism Stroke Arrhythmias Prosthetic valves Fontan 

References

  1. 1.
    Ihenacho HN, Fletcher DJ, Breeze GR, Stuart J. Consumption coagulopathy in congenital heart-disease. Lancet. 1973;1:231–4.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Perloff JK, Marelli AJ, Miner PD. Risk of stroke in adults with cyanotic congenital heart disease. Circulation. 1993;87:1954–9.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Ammash N, Warnes CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol. 1996;28:768–72.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Rosenthal DN, Friedman AH, Kleinman CS, Kopf GS, Rosenfeld LE, Hellenbrand WE. Thromboembolic complications after Fontan operations. Circulation. 1995;92:II287–93.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL. Thrombus formation after the Fontan operation. Ann Thorac Surg. 2001;71:1990–4.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Seipelt RG, Franke A, Vazquez-Jimenez JF, et al. Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches. Ann Thorac Surg. 2002;74:556–62.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Porcelli R, Moskowitz BC, Cetta F, et al. Heparin-induced thrombocytopenia with associated thrombosis in children after the Fontan operation: report of two cases. Tex Heart Inst J. 2003;30:58–61.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Varma C, Warr MR, Hendler AL, Paul NS, Webb GD, Therrien J. Prevalence of “silent” pulmonary emboli in adults after the Fontan operation. J Am Coll Cardiol. 2003;41:2252–8.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Kaulitz R, Ziemer G, Rauch R, et al. Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis). J Thorac Cardiovasc Surg. 2005;129:569–75.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Broberg CS, Ujita M, Prasad S, et al. Pulmonary arterial thrombosis in eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. J Am Coll Cardiol. 2007;50:634–42.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Khairy P, Fernandes SM, Mayer JE Jr, et al. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation. 2008;117:85–92.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Khairy P. Thrombosis in congenital heart disease. Expert Rev Cardiovasc Ther. 2013;11:1579–82.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Marrone C, Galasso G, Piccolo R, et al. Antiplatelet versus anticoagulation therapy after extracardiac conduit Fontan: a systematic review and meta-analysis. Pediatr Cardiol. 2011;32:32–9.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Giglia TM, Massicotte MP, Tweddell JS, et al. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Circulation. 2013;128:2622–703.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Alsaied T, Alsidawi S, Allen CC, Faircloth J, Palumbo JS, Veldtman GR. Strategies for thromboprophylaxis in Fontan circulation: a meta-analysis. Heart. 2015;101:1731–7.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Ohuchi H, Yasuda K, Miyazaki A, et al. Prevalence and predictors of haemostatic complications in 412 Fontan patients: their relation to anticoagulation and haemodynamics. Eur J Cardiothorac Surg. 2015;47:511–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Keraliya AR, Murphy DJ, Steigner ML, Blankstein R. Thrombus in hypoplastic aorta: an uncommon cause of acute myocardial infarction. J Cardiovasc Comput Tomogr. 2016;10:263–4.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Atz AM, Zak V, Mahony L, et al. Longitudinal outcomes of patients with single ventricle after the Fontan procedure. J Am Coll Cardiol. 2017;69:2735–44.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Alsaied T, Bokma JP, Engel ME, et al. Factors associated with long-term mortality after Fontan procedures: a systematic review. Heart. 2017;103:104–10.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Valente AM, Bhatt AB, Cook S, et al. The CALF (congenital heart disease in adults lower extremity systemic venous health in Fontan patients) study. J Am Coll Cardiol. 2010;56:144–50.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Virchow R. Thrombose und Embolie. Gefässentzündung und septische Infektion. Gesammelte Abhandlungen zur wissenschaftlichen Medicin. 1856. pp. 219–752.Google Scholar
  22. 22.
    Giglia TM, Witmer C. Bleeding and thrombosis in pediatric cardiac intensive care. Pediatr Crit Care Med. 2016;17:S287–95.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Giglia TM, Witmer C. Hematologic aspects of pediatric and adolescent heart disease: bleeding, clotting and blood component abnormalities in Moss & Adams Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult, 9th ed. In: Allen HDS, Robert E, Penny DJ, Feltes TF, Cetta F, editors. Moss & Adams’ heart disease in infants, children, and adolescents, including the fetus and young adult. Philadelphia: Lippincott Williams & Wilkins; 2016. p. 1900.Google Scholar
  24. 24.
    Wolberg AS, Aleman MM, Leiderman K, Machlus KR. Procoagulant activity in hemostasis and thrombosis: Virchow’s triad revisited. Anesth Analg. 2012;114:275–85.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Waniewski J, Kurowska W, Mizerski JK, et al. The effects of graft geometry on the patency of a systemic-to-pulmonary shunt: a computational fluid dynamics study. Artif Organs. 2005;29:642–50.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Ravn HB, Hjortdal VE, Stenbog EV, et al. Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection. Heart. 2001;85:61–5.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell. 1996;84:289–97.CrossRefGoogle Scholar
  28. 28.
    Jaggers JJ, Neal MC, Smith PK, Ungerleider RM, Lawson JH. Infant cardiopulmonary bypass: a procoagulant state. Ann Thorac Surg. 1999;68:513–20.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Guay J, Ruest P, Lortie L. Cardiopulmonary bypass induces significant platelet activation in children undergoing open-heart surgery. Eur J Anaesthesiol. 2004;21:953–6.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Heying R, van Oeveren W, Wilhelm S, et al. Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity. Crit Care (London England). 2006;10:R165.CrossRefGoogle Scholar
  31. 31.
    Jaggers J, Lawson JH. Coagulopathy and inflammation in neonatal heart surgery: mechanisms and strategies. Ann Thorac Surg. 2006;81(6):S2360.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Tomita H, Yamada O, Ohuchi H, et al. Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations. Cardiol Young. 2001;11:62–6.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Jahangiri M, Shore D, Kakkar V, Lincoln C, Shinebourne E. Coagulation factor abnormalities after the Fontan procedure and its modifications. J Thorac Cardiovasc Surg. 1997;113:989–92; discussion 92–3PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Jahangiri M, Kreutzer J, Zurakowski D, Bacha E, Jonas RA. Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation. J Thorac Cardiovasc Surg. 2000;120:778–82.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Odegard KC, McGowan FX Jr, DiNardo JA, et al. Coagulation abnormalities in patients with single-ventricle physiology precede the Fontan procedure. J Thorac Cardiovasc Surg. 2002;123:459–65.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Odegard KC, McGowan FX Jr, Zurakowski D, et al. Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure. Ann Thorac Surg. 2002;73:1770–7.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Odegard KC, McGowan FX Jr, Zurakowski D, et al. Procoagulant and anticoagulant factor abnormalities following the Fontan procedure: increased factor VIII may predispose to thrombosis. J Thorac Cardiovasc Surg. 2003;125:1260–7.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Odegard KC, Zurakowski D, Hornykewycz S, et al. Evaluation of the coagulation system in children with two-ventricle congenital heart disease. Ann Thorac Surg. 2007;83:1797–803.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Odegard KC, Zurakowski D, DiNardo JA, et al. Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion. J Thorac Cardiovasc Surg. 2009;137:934–41.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Horigome H, Murakami T, Isobe T, Nagasawa T, Matsui A. Soluble P-selectin and thrombomodulin-protein C-Protein S pathway in cyanotic congenital heart disease with secondary erythrocytosis. Thromb Res. 2003;112:223–7.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Rask O, Hanseus K, Ljung R, Strandberg K, Berntorp E. Lower incidence of procoagulant abnormalities during follow-up after creation of the Fontan circulation in children. Cardiol Young. 2009;19:152–8.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Levin E, Wu J, Devine DV, et al. Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid. Thromb Haemost. 2000;83:54–9.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Binotto MA, Maeda NY, Lopes AA. Evidence of endothelial dysfunction in patients with functionally univentricular physiology before completion of the Fontan operation. Cardiol Young. 2005;15:26–30.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Thornburg CD, Smith PB, Smithwick ML, Cotten CM, Benjamin DK Jr. Association between thrombosis and bloodstream infection in neonates with peripherally inserted catheters. Thromb Res. 2008;122:782–5.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials. BMJ. 1998;316:969–75.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    O'Connor MJ, Ravishankar C, Ballweg JA, et al. Early systemic-to-pulmonary artery shunt intervention in neonates with congenital heart disease. J Thorac Cardiovasc Surg. 2011;142:106–12.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Silversides CK, Granton JT, Konen E, Hart MA, Webb GD, Therrien J. Pulmonary thrombosis in adults with Eisenmenger syndrome. J Am Coll Cardiol. 2003;42:1982–7.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Saha A, Balakrishnan KG, Jaiswal PK, et al. Prognosis for patients with Eisenmenger syndrome of various aetiology. Int J Cardiol. 1994;45:199–207.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Daliento L, Somerville J, Presbitero P, et al. Eisenmenger syndrome. Factors relating to deterioration and death. Eur Heart J. 1998;19:1845–55.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Niwa K, Perloff JK, Kaplan S, Child JS, Miner PD. Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart. J Am Coll Cardiol. 1999;34:223–32.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Giannakoulas G, Boutsikou M. The Gordian knot of thromboembolism in congenital heart disease. Heart. 2015;101:1523–4.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Jensen AS, Idorn L, Thomsen C, et al. Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease. Heart. 2015;101:1540–6.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Manlhiot C, Menjak IB, Brandao LR, et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation. 2011;124:1511–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Giglia TM, Petrosa WL, Veneziale K, et al. Use of PC4 database in a prospective cohort study of hospital-acquired thrombosis in pediatric cardiac in-patients. J Am Coll Cardiol. 2016;67:976.CrossRefGoogle Scholar
  55. 55.
    Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol. 2007;82:777–82.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Lim W, Meade M, Lauzier F, et al. Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients*. Crit Care Med. 2015;43:401–10.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979–1998: an analysis using multiple-cause mortality data. Arch Intern Med. 2003;163:1711–7.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    The Surgeon General’s Call to Action to Prevention Deep Vein Thrombosis and Pulmonary Embolism. In: Services UDoHaH, editor. http://www.surgeongeneral.gov/topics/deepvein/calltoaction/call-to-action-ondvt-2008.pdf.2008.
  59. 59.
    Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107:I9–16.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Di Nisio M, van Es N, Buller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388:3060–73.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8:2450–7.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706–14.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Nendaz M, Spirk D, Kucher N, et al. Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE). Thromb Haemost. 2014;111:531–8.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011;365:2463–72.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;318:1162–73.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Galanaud JP, Sevestre-Pietri MA, Bosson JL, et al. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009;102:493–500.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    White RH, Brunson A, Romano PS, Li Z, Wun T. Outcomes after vena cava filter use in noncancer patients with acute venous thromboembolism: a population-based study. Circulation. 2016;133:2018–29.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315–52.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788–830.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation. 2009;120:1679–86.CrossRefGoogle Scholar
  71. 71.
    Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J. 2005;26:2325–33.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Walkey AJ, Hogarth DK, Lip GYH. Optimizing atrial fibrillation management: from ICU and beyond. Chest. 2015;148:859–64.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Pisters R, Lane DA, Marin F, Camm AJ, Lip GY. Stroke and thromboembolism in atrial fibrillation. Circulation. 2012;76:2289–304.CrossRefGoogle Scholar
  74. 74.
    Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Khairy P, Aboulhosn J, Broberg CS, et al. Thromboprophylaxis for atrial arrhythmias in congenital heart disease: a multicenter study. Int J Cardiol. 2016;223:729–35.CrossRefGoogle Scholar
  76. 76.
    Masuda K, Ishizu T, Niwa K, et al. Increased risk of thromboembolic events in adult congenital heart disease patients with atrial tachyarrhythmias. Int J Cardiol. 2017;234:69–75.CrossRefGoogle Scholar
  77. 77.
    Heidendael JF, Bokma JP, de Groot JR, Koolbergen DR, Mulder BJ, Bouma BJ. Weighing the risks: thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease. Int J Cardiol. 2015;186:315–20.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Lanz J, Brophy JM, Therrien J, Kaouache M, Guo L, Marelli AJ. Stroke in adults with congenital heart disease: incidence, cumulative risk, and predictors. Circulation. 2015;132:2385–94.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Mandalenakis Z, Rosengren A, Lappas G, Eriksson P, Hansson PO, Dellborg M. Ischemic stroke in children and young adults with congenital heart disease. J Am Heart Assoc. 2016;5:e003071.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e143–263.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Heart Rhythm. 2014;11:e102–65.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Holst KA, Dearani JA, Burkhart HM, et al. Reoperative multivalve surgery in adult congenital heart disease. Ann Thorac Surg. 2013;95:1383–9.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Brennan JM, Edwards FH, Zhao Y, et al. Long-term safety and effectiveness of mechanical versus biologic aortic valve prostheses in older patients: results from the Society of Thoracic Surgeons Adult Cardiac Surgery National Database. Circulation. 2013;127:1647–55.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Heras M, Chesebro JH, Fuster V, et al. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol. 1995;25:1111–9.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89:635–41.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Massel DR, Little SH. Antiplatelet and anticoagulation for patients with prosthetic heart valves. Cochrane Database Syst Rev. 2013;(7):CD003464.Google Scholar
  87. 87.
    Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521–643.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Nishimura RA, Otto CM, Bonow RO, et al. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2017;135:e1159–e95.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Russo A, Grigioni F, Avierinos JF, et al. Thromboembolic complications after surgical correction of mitral regurgitation incidence, predictors, and clinical implications. J Am Coll Cardiol. 2008;51:1203–11.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart. 2007;93:137–42.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e326S–50S.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Seshadri N, Goldhaber SZ, Elkayam U, et al. The clinical challenge of bridging anticoagulation with low-molecular-weight heparin in patients with mechanical prosthetic heart valves: an evidence-based comparative review focusing on anticoagulation options in pregnant and nonpregnant patients. Am Heart J. 2005;150:27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Spyropoulos AC, Turpie AG, Dunn AS, et al. Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN registry). Am J Cardiol. 2008;102:883–9.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Barbetseas J, Nagueh SF, Pitsavos C, Toutouzas PK, Quinones MA, Zoghbi WA. Differentiating thrombus from pannus formation in obstructed mechanical prosthetic valves: an evaluation of clinical, transthoracic and transesophageal echocardiographic parameters. J Am Coll Cardiol. 1998;32:1410–7.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Tanis W, Habets J, van den Brink RB, Symersky P, Budde RP, Chamuleau SA. Differentiation of thrombus from pannus as the cause of acquired mechanical prosthetic heart valve obstruction by non-invasive imaging: a review of the literature. Eur Heart J Cardiovasc Imaging. 2014;15:119–29.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Egbe AC, Pislaru SV, Pellikka PA, et al. Bioprosthetic valve thrombosis versus structural failure: clinical and echocardiographic predictors. J Am Coll Cardiol. 2015;66:2285–94.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Pislaru SV, Hussain I, Pellikka PA, et al. Misconceptions, diagnostic challenges and treatment opportunities in bioprosthetic valve thrombosis: lessons from a case series. Eur J Cardiothorac Surg. 2015;47:725–32.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Manlhiot C, Brandao LR, Kwok J, et al. Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation. J Pediatr. 2012;161:513–9.e3.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Pujol C, Niesert AC, Engelhardt A, et al. Usefulness of direct oral anticoagulants in adult congenital heart disease. Am J Cardiol. 2016;117:450–5.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Linhardt RJ, Gunay NS. Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost. 1999;25(Suppl 3):5–16.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Damus PS, Hicks M, Rosenberg RD. Anticoagulant action of heparin. Nature. 1973;246:355–7.CrossRefGoogle Scholar
  103. 103.
    Rosenberg RD, Lam L. Correlation between structure and function of heparin. Proc Natl Acad Sci U S A. 1979;76:1218–22.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Lindahl U, Backstrom G, Hook M, Thunberg L, Fransson LA, Linker A. Structure of the antithrombin-binding site in heparin. Proc Natl Acad Sci U S A. 1979;76:3198–202.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e24S–43S.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Estes JW. The kinetics of heparin. Ann N Y Acad Sci. 1971;179:187–204.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Murphy MS, John PR, Mayer AD, Buckels JA, Kelly DA. Heparin therapy and bone fractures. Lancet. 1992;340:1098.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Sackler JP, Liu L. Heparin-induced osteoporosis. Br J Radiol. 1973;46:548–50.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330–5.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Warkentin TE, Hayward CP, Boshkov LK, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood. 1994;84:3691–9.PubMedPubMedCentralGoogle Scholar
  111. 111.
    Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood. 2000;96:1703–8.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Pouplard C, May MA, Iochmann S, et al. Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia. Circulation. 1999;99:2530–6.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Smythe MA, Koerber JM, Mattson JC. The incidence of recognized heparin-induced thrombocytopenia in a large, tertiary care teaching hospital. Chest. 2007;131:1644–9.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710–5.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129:2864–72.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007;83:575–82.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003;76:2121–31.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Cuker A, Arepally G, Crowther MA, et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010;8:2642–50.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Lillo-Le Louet A, Boutouyrie P, Alhenc-Gelas M, et al. Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost. 2004;2:1882–8.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4:759–65.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Linkins LA, Dans AL, Moores LK, et al. 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:e495S–530S.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Bhatt VR, Aryal MR, Shrestha R, Armitage JO. Fondaparinux-associated heparin-induced thrombocytopenia. Eur J Haematol. 2013;91:437–41.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286–92.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Paolucci F, Frasa H, Van Aarle F, et al. Two sensitive and rapid chromogenic assays of fondaparinux sodium (Arixtra) in human plasma and other biological matrices. Clin Lab. 2003;49:451–60.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Elmer J, Wittels KA. Emergency reversal of pentasaccharide anticoagulants: a systematic review of the literature. Transfus Med (Oxford, England). 2012;22:108–15.CrossRefGoogle Scholar
  126. 126.
    Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood. 1999;93:1798–808.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th). Chest. 2008;133:160S–98S.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Baruch L. Laboratory monitoring of anticoagulant medications: focus on novel oral anticoagulants. Postgrad Med. 2013;125:135–45.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Wright C, Brown R, Cuker A. Laboratory measurement of the direct oral anticoagulants: indications and impact on management in clinical practice. Int J Lab Hematol. 2017;39 Suppl 1:31–6.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Schiele F, van Ryn J, Litzenburger T, Ritter M, Seeliger D, Nar H. Structure-guided residence time optimization of a dabigatran reversal agent. MAbs. 2015;7:871–80.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. New Engl J Med. 2015;373:511–20.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Stecher A, Vene N, Mavri A, Mijovski MB, Krevel B, Gradisek P. Late rebound of dabigatran levels after idarucizumab reversal in two patients with severe renal failure. Eur J Anaesthesiol. 2017;34:400–2.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Simon A, Domanovits H, Ay C, Sengoelge G, Levy JH, Spiel AO. The recommended dose of idarucizumab may not always be sufficient for sustained reversal of dabigatran. J Thromb Haemost. 2017;15:1317–21.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Khadzhynov D, Wagner F, Formella S, et al. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease. Thromb Haemost. 2013;109:596–605.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Yates S, Sarode R. Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects. Curr Opin Hematol. 2013;20:552–7.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Siegal DM, Garcia DA, Crowther MA. How I treat target-specific oral anticoagulant-associated bleeding. Blood. 2014;123:1152–8.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Cowell RP. Direct oral anticoagulants: integration into clinical practice. Postgrad Med J. 2014;90:529–39.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Sun JC, Davidson MJ, Lamy A, Eikelboom JW. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet. 2009;374:565–76.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e576S–600S.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Desai S, Kavinsky C. Localized left atrial administration of tPA for the treatment of mechanical mitral valve thrombosis. Catheter Cardiovasc Interv. 2008;72:151–5.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Johnson JA, Rauh RA, Phillips SD, Cetta F. Thrombolytic therapy in the treatment of right-sided prosthetic valve thrombosis in adults with congenital heart disease. Congenit Heart Dis. 2011;6:266–8.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Taherkhani M, Hashemi SR, Hekmat M, Safi M, Taherkhani A, Movahed MR. Thrombolytic therapy for right-sided mechanical pulmonic and tricuspid valves: the largest survival analysis to date. Tex Heart Inst J. 2015;42:543–7.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Ozturk S, Erdem F, Ozturk S, Ayhan S. Successful thrombolytic therapy in a patient with congenital corrected transposition of the great arteries. Acta Med Acad. 2016;45:158–62.PubMedPubMedCentralGoogle Scholar
  145. 145.
    Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33:1500–10.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Monagle P, AKC C, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e737S–801S.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Therese M. Giglia
    • 1
    Email author
  • Char M. Witmer
    • 1
  • Yuli Y. Kim
    • 1
  1. 1.Children’s Hospital of PhiladelphiaPhiladelphiaUSA

Personalised recommendations