Semin Thromb Hemost 2003; 29(6): 547-556
DOI: 10.1055/s-2004-815637
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Thrombosis in Pediatric Cardiac Patients

Paul Monagle
  • Associate Professor, Director, Division of Laboratory Services, Royal Children's Hospital, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Further Information

Publication History

Publication Date:
13 January 2004 (online)

ABSTRACT

Cardiac disease and thrombosis are intimately related in adults, but primary myocardial infarction in children is rare. Homozygous familial hyperlipidemia occurs in approximately 1 million children, and causes severe coronary artery disease during childhood. Kawasaki's disease is an acquired inflammatory disorder, which, if untreated, leads to coronary artery aneurysms and subsequent myocardial infarction. The current understanding of the pathophysiology and management of these conditions is discussed. More commonly, the relationship between cardiac disease in children and thrombosis is that children being treated for congenital structural cardiac disease develop iatrogenic thrombosis, most commonly precipitated by central venous access. The epidemiology of common treatment-induced thrombosis is described, and management guidelines presented. Finally, many cardiac surgical procedures increase the risk of thrombosis, and prophylactic antithrombotic therapy is commonly used. The current evidence for prophylaxis in different clinical situations is presented. Additional study is required in all areas to improve the outcome for children affected by cardiac disease and thrombosis.

REFERENCES

  • 1 Haber C, Kwiterovich Jr O P. Dyslipoproteinemia and xanthomatosis.  Pediatr Dermatol . 1984;  1 261-280
  • 2 West R J, Lloyd J K. Hypercholesterolemia in childhood.  Adv Pediatr . 1979;  26 1-34
  • 3 Fallat R W, Tsang R C, Glueck C J. Hypercholesterolemia and hypertriglyceridemia in children.  Prev Med . 1974;  3 390-405
  • 4 Haitas B, Baker S G, Meyer T E. et al . Natural history and cardiac manifestations of homozygous familial hypercholesterolaemia.  Q J Med . 1990;  76 731-740
  • 5 Rose V, Wilson G, Steiner G. Familial hypercholesterolemia: report of coronary death at age 3 in a homozygous child and prenatal diagnosis in a heterozygous sibling.  J Pediatr . 1982;  100 757-759
  • 6 Sprecher D L, Schaefer E J, Kent K M. et al . Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients.  Am J Cardiol . 1984;  54 20-30
  • 7 Hoeg J M. Familial hypercholesterolemia. What the zebra can teach us about the horse.  JAMA . 1994;  271 543-546
  • 8 Goldstein J L, Brown M S. The LDL receptor defect in familial hypercholesterolemia. Implications for pathogenesis and therapy.  Med Clin North Am . 1982;  66 335-362
  • 9 Williams M L. Death of a child as a result of familial hypercholesterolaemia Med J Aust .  1989;  150 93-94
  • 10 Clemens P, Beisiegel U, Steinhagen-Thiessen E. Family study in familial hypercholesterolemia with a receptor-negative homozygous 9-year-old boy.  Helv Paediatr Acta . 1986;  41 173-182
  • 11 Goldstein J, Brown M. Familial hyercholesterolemia. In: Stanbury JB, ed. Metabolic Basis of Inherited Disease, Chapter 33 New York: McGraw Hill 1989: 672-712
  • 12 Leonard J V, Clarke M, Macartney F J. et al . Progression of atheroma in homozygous familial hypercholesterolaemia during regular plasma exchange (letter).  Lancet . 1981;  2 811
  • 13 Raper S E, Grossman M, Rader D J. et al . Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia Ann Surg .  1996;  223 116-126
  • 14 Celermajer D S, Sorensen K E, Gooch V M. et al . Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.  Lancet . 1992;  340 1111-1115
  • 15 Sorensen K E, Celermajer D S, Georgakopoulos D. et al . Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.  J Clin Invest . 1994;  93 50-55
  • 16 Hegele R A, Connelly P W, Cullen-Dean G. et al . Elevated plasma lipoprotein(a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia.  Am J Cardiol . 1993;  72 402-406
  • 17 Mouratidis B, Vaughan-Neil E F, Gilday D L. et al . Detection of silent coronary artery disease in adolescents and young adults with familial hypercholesterolemia by single-photon emission computed tomography thallium-201 scanning.  Am J Cardiol . 1992;  70 1109-1112
  • 18 Rubinsztein D C, Raal F J, Seftel H C. et al . Characterization of six patients who are double heterozygotes for familial hypercholesterolemia and familial defective apo B-100.  Arterioscler Thromb . 1993;  13 1076-1081
  • 19 Rauh G, Keller C, Kormann B. et al . Familial defective apolipoprotein B100: clinical characteristics of 54 cases.  Atherosclerosis . 1992;  92 233-241
  • 20 Salen G, Horak I, Rothkopf M. et al . Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis.  J Lipid Res . 1985;  26 1126-1133
  • 21 Kawasaki T. Discovery of Kawasaki disease (muco-cutaneous lymph node syndrome) and its research activities.  Nippon Rinsho . 1976;  34 222-227
  • 22 Durongpisitkul K, Gururaj V J, Park J M. et al . The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment.  Pediatrics . 1995;  96 1057-1061
  • 23 Furusho K, Kamiya T, Nakano H. et al . High-dose intravenous gammaglobulin for Kawasaki disease.  Lancet . 1984;  2 1055-1058
  • 24 Newburger J W, Takahashi M, Burns J C. et al . The treatment of Kawasaki syndrome with intravenous gamma globulin.  N Engl J Med . 1986;  315 341-347
  • 25 Newburger J W, Takahashi M, Beiser A S. et al . A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome.  N Engl J Med . 1991;  324 1633-1639
  • 26 Koren G, Rose V, Lavi S. et al . Probable efficacy of high-dose salicylates in reducing coronary involvement in Kawasaki disease.  JAMA . 1985;  254 767-769
  • 27 Daniels S R, Specker B, Capannari T E. et al . Correlates of coronary artery aneurysm formation in patients with Kawasaki disease.  Am J Dis Child . 1987;  141 205-207
  • 28 Williams R V, Wilke V M, Tani L Y. et al . Does abciximab enhance regression of coronary aneurysms resulting from Kawasaki disease?.  Pediatrics . 2002;  109 E4
  • 29 Suzuki A, Kamiya T, Ono Y. et al . Myocardial ischemia in Kawasaki disease: follow-up study by cardiac catheterization and coronary angiography.  Pediatr Cardiol . 1988;  9 1-5
  • 30 Kato H, Sugimura T, Akagi T. et al . Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients.  Circulation . 1996;  94 1379-1385
  • 31 Gersony W M. Diagnosis and management of Kawasaki disease.  JAMA . 1991;  265 2699-2703
  • 32 Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysm in Kawasaki disease: an angiographic study.  J Pediatr . 1987;  111 705-710
  • 33 The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction.  N Engl J Med . 1993;  329 1615-1622
  • 34 Kitamura S, Kameda Y, Kawashima Y. Surgery for Kawasaki disease.  Adv Card Surg . 1997;  9 177-194
  • 35 Smith C, Green R M. Pediatric vascular injuries.  Surgery . 1981;  90 20-31
  • 36 Perry M O. Iatrogenic injuries of arteries in infants.  Surg Gynecol Obstet . 1983;  157 415-418
  • 37 Burrows P E, Benson L N, Williams W G. et al . Iliofemoral arterial complications of balloon angioplasty for systemic obstructions in infants and children.  Circulation . 1990;  82 1697-1704
  • 38 Mortensson W, Hallbook T, Lundstrom N R. Percutaneous catheterization of the femoral vessels in children. II. Thrombotic occlusion of the catheterized artery: frequency and causes.  Pediatr Radiol . 1975;  4 1-9
  • 39 Mortensson W. Angiography of the femoral artery following percutaneous catheterization in infants and children.  Acta Radiol . 1976;  17 581-593
  • 40 Padmanabhan J, Krovetz L J, Varghese P J. et al . Effect of topical papaverine in preventing thrombosis following arteriotomies. A double-blind study in infants and children.  J Pediatr . 1972;  81 792-793
  • 41 Freed M D, Keane J F, Rosenthal A. The use of heparinization to prevent arterial thrombosis after percutaneous cardiac catheterization in children.  Circulation . 1974;  50 565-569
  • 42 Ino T, Benson L N, Freedom R M. et al . Thrombolytic therapy for femoral artery thrombosis after pediatric cardiac catheterization.  Am Heart J . 1988;  115 633-639
  • 43 Rao P S, Thapar M K, Rogers Jr H J. et al . Effect of intraarterial injection of heparin on the complications of percutaneous arterial catheterization in infants and children.  Cathet Cardiovasc Diagn . 1981;  7 235-246
  • 44 Butt W, Shann F, McDonnell G. et al . Effect of heparin concentration and infusion rate on the patency of arterial catheters.  Crit Care Med . 1987;  15 230-232
  • 45 Saxena A, Gupta R, Kumar R K. et al . Predictors of arterial thrombosis after diagnostic cardiac catheterization in infants and children randomized to two heparin dosages.  Cathet Cardiovasc Diagn . 1997;  41 400-403
  • 46 McFadden P M, Ochsner J L, Mills N. Management of thrombotic complications of invasive arterial monitoring of the upper extremity.  J Cardiovasc Surg (Torino) . 1983;  24 35-39
  • 47 Vlad P, Hohn A, Lambert E C. Retrograde arterial catheterization of the left heart. Experience with 500 infants and children.  Circulation . 1964;  29 787-793
  • 48 Jones J, Hunter D. Consensus methods for medical and health services research.  BMJ . 1995;  311 376-380
  • 49 Stanger P, Heymann M A, Tarnoff H. et al . Complications of cardiac catheterization of neonates, infants, and children. A three-year study.  Circulation . 1974;  50 595-608
  • 50 Hurwitz R A, Franken Jr A E, Girod D A. et al . Angiographic determination of arterial patency after percutaneous catheterization in infants and small children.  Circulation . 1977;  56 102-105
  • 51 Girod D A, Hurwitz R A, Caldwell R L. Heparinization for prevention of thrombosis following pediatric percutaneous arterial catheterization.  Pediatr Cardiol . 1982;  3 175-180
  • 52 Wessel D L, Keane J F, Fellows K E. et al . Fibrinolytic therapy for femoral arterial thrombosis after cardiac catheterization in infants and children.  Am J Cardiol . 1986;  58 347-351
  • 53 Gagnon R M, Goudreau E, Joyal F. et al . The role of intravenous streptokinase in acute arterial occlusions after cardiac catheterization.  Cathet Cardiovasc Diagn . 1985;  11 409-412
  • 54 Zenz W, Muntean W, Beitzke A. et al . Tissue plasminogen activator (alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children.  Br Heart J . 1993;  70 382-385
  • 55 Brus F, Witsenburg M, Hofhuis W J. et al . Streptokinase treatment for femoral artery thrombosis after arterial cardiac catheterisation in infants and children.  Br Heart J . 1990;  63 291-294
  • 56 Kothari S S, Kumar R K, Varma S. et al . Thrombolytic therapy in infants for femoral artery thrombosis following cardiac catheterisation.  Indian Heart J . 1996;  48 246-248
  • 57 Freed M D, Rosenthal A, Fyler D. Attempts to reduce arterial thrombosis after cardiac catheterization in children: use of percutaneous technique and aspirin.  Am Heart J . 1974;  87 283-286
  • 58 Kern I B. Management of children with chronic femoral artery obstruction.  J Pediatr Surg . 1977;  12 83-90
  • 59 Taylor Jr M L, Troutman R, Feliciano P. et al . Late complications after femoral artery catheterization in children less than five years of age.  J Vasc Surg . 1990;  11 297-304
  • 60 Celermajer D S, Robinson J T, Taylor J F. Vascular access in previously catheterised children and adolescents: a prospective study of 131 consecutive cases.  Br Heart J . 1993;  70 554-557
  • 61 Taussig H B. Long-time observations on the Blalock-Taussig operation IX. Single ventricle (with apex to the left).  Johns Hopkins Med J . 1976;  139 69-76
  • 62 Truccone N J, Bowman Jr O F, Malm J R. et al . Systemic-pulmonary arterial shunts in the first year of life.  Circulation . 1974;  49 508-511
  • 63 Godart F, Qureshi S A, Simha A. et al . Effects of modified and classic Blalock-Taussig shunts on the pulmonary arterial tree.  Ann Thorac Surg . 1998;  66 512-517
  • 64 Tsai K T, Chang C H, Lin P J. Modified Blalock-Taussig shunt: statistical analysis of potential factors influencing shunt outcome.  J Cardiovasc Surg (Torino) . 1996;  37 149-152
  • 65 Gladman G, McCrindle B W, Williams W G. et al . The modified Blalock-Taussig shunt: clinical impact and morbidity in Fallot's tetralogy in the current era.  J Thorac Cardiovasc Surg . 1997;  114 25-30
  • 66 Bogats G, Kertesz E, Katona M. et al . Modified Blalock-Taussig shunt using allograft saphenous vein: six years' experience.  Ann Thorac Surg . 1996;  61 58-62
  • 67 Ohuchi H, Okabe H, Nagata N. et al . Long-term patency after the Blalock-Taussig operation-comparison between classic and modified shunts.  Nippon Kyobu Geka Gakkai Zasshi . 1996;  44 1108-1113
  • 68 Zahn E M, Chang A C, Aldousany A. et al . Emergent stent placement for acute Blalock-Taussig shunt obstruction after stage 1 Norwood surgery.  Cathet Cardiovasc Diagn . 1997;  42 191-194
  • 69 Takanashi Y, Tomizawa Y, Noishiki Y. et al . Calcified EPTFE vascular prosthesis in the Blalock-Taussig shunt after 4 years of implantation: a case report.  Kyobu Geka . 1997;  50 71-73
  • 70 Berger R M, Bol-Raap G, Hop W J. et al . Heparin as a risk factor for perigraft seroma complicating the modified Blalock-Taussig shunt.  J Thorac Cardiovasc Surg . 1998;  116 286-292
  • 71 Klinge J, Hofbeck M, Ries M. et al . Thrombolysis of modified Blalock-Taussig shunts in childhood with recombinant tissue-type plasminogen activator.  Z Kardiol . 1995;  84 476-480
  • 72 Alcibar J, Cabrera A, Onate A. et al . Angioplasty of the stenotic Blalock-Taussig.  Rev Esp Cardiol . 1994;  47 819-823
  • 73 Ries M, Singer H, Hofbeck M. Thrombolysis of a modified Blalock-Taussig shunt with recombinant tissue plasminogen activator in a newborn infant with pulmonary atresia and ventricular septal defect.  Br Heart J . 1994;  72 201-202
  • 74 Boulden T F, Tonkin I L, Burton E M. et al . Case of the day. Pediatric. Mycotic pseudoaneurysm and thrombosis of modified left Blalock-Taussig shunt.  Radiographics . 1990;  10 119-121
  • 75 Ahmadi A, Mocellin R, Henglein D. et al . Modified Blalock-Taussig anostomosis. Its significance within the scope of surgical treatment of Tetralogy of Fallot.  Monatsschr Kinderheilkd . 1988;  136 130-134
  • 76 Brandt B, Camacho J A, Mahoney L T. et al . Growth of the pulmonary arteries following Blalock-Taussig shunt.  Ann Thorac Surg . 1986;  42 S1-S4
  • 77 Tamisier D, Vouhe P R, Vernant F. et al . Modified Blalock-Taussig shunts: results in infants less than 3 months of age.  Ann Thorac Surg . 1990;  49 797-801
  • 78 Mullen J C, Lemermeyer G, Bentley M J. Modified Blalock-Taussig shunts: to heparinize or not to heparinize?.  Can J Cardiol . 1996;  12 645-647
  • 79 Rajani R M, Dalvi B V, Kulkarni H L. et al . Acutely blocked Blalock-Taussig shunt following cardiac catheterization: successful recanalization with intravenous streptokinase.  Am Heart J . 1990;  120 1238-1239
  • 80 Hijazi Z M. Stenting for postoperative congenital heart disease in infants.  Cathet Cardiovasc Diagn . 1997;  42 195-198
  • 81 Monagle P, Cochrane A, McCrindle B. et al . Thromboembolic complications after Fontan procedures-the role of prophylactic anticoagulation.  J Thorac Cardiovasc Surg . 1998;  115 493-498
  • 82 Zahn E M, Lima V C, Benson L N. et al . Use of endovascular stents to increase pulmonary blood flow in pulmonary atresia with ventricular septal defect.  Am J Cardiol . 1992;  70 411-412
  • 83 Sade R, Ballenger J F, Hohn A. et al . Cardiac valve replacement in children: Comparison of tissue with mechanical prostheses.  J Thorac Cardiovasc Surg . 1979;  78 123-127
  • 84 Brown J W, Dunn J M, Spooner E. et al . Late spontaneous disruption of a porcine xenograft mitral valve. Clinical, hemodynamic, echocardiographic, and pathological findings.  J Thorac Cardiovasc Surg . 1978;  75 606-611
  • 85 Geha A S, Laks H, Stansel Jr C H. et al . Late failure of porcine valve heterografts in children.  J Thorac Cardiovasc Surg . 1979;  78 351-364
  • 86 Silver M M, Pollock J, Silver M D. et al . Calcification in porcine xenograft valves in children.  Am J Cardiol . 1980;  45 685-689
  • 87 Dunn J M. Porcine valve durability in children.  Ann Thorac Surg . 1981;  32 357-368
  • 88 Williams W G, Pollack J C, Geiss D M. et al . Experience with aortic and mitral valve replacement in children.  J Thorac Cardiovasc Surg . 1981;  81 326-333
  • 89 Miller D, Stinson E, Oyer P. et al . The durability of porcine xenograft valves and conduits in children.  Circulation . 1982;  66(suppl I, Pt 2) I172-I185
  • 90 Odell J. Calcification of porcine bioprostheses in children. In: Cohn L, Gallucci V, eds. Cardiac Bioprostheses: Proceedings of the Second International Symposium New York: Yorke Medical Books 1982: 231
  • 91 Williams D B, Danielson G K, McGoon D C. et al . Porcine heterograft valve replacement in children.  J Thorac Cardiovasc Surg . 1982;  84 446-450
  • 92 Champsaur G, Robin J, Tronc F. et al . Mechanical valve in aortic position is a valid option in children and adolescents.  Eur J Cardiothorac Surg . 1997;  11 117-122
  • 93 Yankah A C, Alexi-Meskhishvili V, Weng Y. et al . Performance of aortic and pulmonary homografts in the right ventricular outflow tract in children.  J Heart Valve Dis . 1995;  4 392-395
  • 94 Monagle P, Michelson A D, Bovill E. et al . Antithrombotic therapy in children.  Chest . 2001;  119 344S-370S
    >