Thrombosis in Childhood Cancer

  • Geoffrey A. Allen
  • Rukhmi Bhat
Part of the Cancer Treatment and Research book series (CTAR, volume 148)

Over the past five decades, the survival rate for children diagnosed with oncologic disease has dramatically increased from less than 20% to almost 80%. Accordingly, an area of growing interest and concern is the long-term effects of the patients’ disease and therapy. Thromboembolic events (TEE) occur with greater frequency in children and adults with cancer and have been extensively studied in the latter population. However, given the relative infrequency of TEE in the general pediatric population and paucity of coordinated efforts, information on the incidence, nature and impact of thrombosis in children with cancer has been lacking until recently. In this chapter, we address the salient features of TEEs in the pediatric cancer patient.


Acute Lymphoblastic Leukemia Thrombotic Event Thrombin Generation Pediatric Cancer Patient Hemostatic System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19–25.PubMedGoogle Scholar
  2. 2.
    Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d'Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost. 2000;83:657–660.PubMedGoogle Scholar
  3. 3.
    Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994;83:1251–1257.PubMedGoogle Scholar
  4. 4.
    Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr. 2004;145:563–565.PubMedGoogle Scholar
  5. 5.
    van Ommen CH, Heijboer H, Buller HR, Hirasing RA, Heijmans HS, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr. 2001;139:676–681.PubMedGoogle Scholar
  6. 6.
    Kuhle S, Lau A, Bajzar L, et al. Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with L-asparaginase: an in vitro study. Br J Haematol. 2006;134:526–531.PubMedGoogle Scholar
  7. 7.
    Athale UH, Chan AK. Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of thrombosis in children with acute lymphoblastic leukemia. Thromb Res. 2003;111:125–131.PubMedGoogle Scholar
  8. 8.
    Caruso V, Iacoviello L, Di Castelnuovo A, et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood. 2006;108:2216–2222.PubMedGoogle Scholar
  9. 9.
    Mitchell LG, Andrew M, Hanna K, et al. A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study. Cancer. 2003;97:508–516.PubMedGoogle Scholar
  10. 10.
    Farinasso L, Bertorello N, Garbarini L, et al. Risk factors of central venous lines-related thrombosis in children with acute lymphoblastic leukemia during induction therapy: a prospective study. Leukemia. 2007;21:552–556.PubMedGoogle Scholar
  11. 11.
    Deitcher SR, Gajjar A, Kun L, Heideman RL. Clinically evident venous thromboembolic events in children with brain tumors. J Pediatr. 2004;145:848–850.PubMedGoogle Scholar
  12. 12.
    Tabori U, Beni-Adani L, Dvir R, et al. Risk of venous thromboembolism in pediatric patients with brain tumors. Pediatr Blood Cancer. 2004;43:633–636.PubMedGoogle Scholar
  13. 13.
    Paz-Priel I, Long L, Helman LJ, Mackall CL, Wayne AS. Thromboembolic events in children and young adults with pediatric sarcoma. J Clin Oncol. 2007;25:1519–1524.PubMedGoogle Scholar
  14. 14.
    Gitlin D, Biasucci A. Development of gamma G, gamma A, gamma M, beta IC-beta IA, C 1 esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, plasminogen, alpha 1-antitrypsin, orosomucoid, beta-lipoprotein, alpha 2-macroglobulin, and prealbumin in the human conceptus. J Clin Invest. 1969;48:1433–1446.PubMedGoogle Scholar
  15. 15.
    Reverdiau-Moalic P, Delahousse B, Body G, Bardos P, Leroy J, Gruel Y. Evolution of blood coagulation activators and inhibitors in the healthy human fetus. Blood. 1996;88:900–906.PubMedGoogle Scholar
  16. 16.
    Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72:1651–1657.PubMedGoogle Scholar
  17. 17.
    Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70:165–172.PubMedGoogle Scholar
  18. 18.
    Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood. 1992;80:1998–2005.PubMedGoogle Scholar
  19. 19.
    Mautone A, Giordano P, Montagna O, Quercia M, Altomare M, De Mattia D. Coagulation and fibrinolytic systems in the ill preterm newborn. Acta Paediatr. 1997;86:1100–1104.PubMedGoogle Scholar
  20. 20.
    Israels SJ, Rand ML, Michelson AD. Neonatal platelet function. Semin Thromb Hemost. 2003;29:363–372.PubMedGoogle Scholar
  21. 21.
    Katz JA, Moake JL, McPherson PD, et al. Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma. Blood. 1989;73:1851–1858.PubMedGoogle Scholar
  22. 22.
    Michelson AD. Platelet function in the newborn. Semin Thromb Hemost. 1998;24:507–512.PubMedGoogle Scholar
  23. 23.
    Weinstein MJ, Blanchard R, Moake JL, Vosburgh E, Moise K. Fetal and neonatal von Willebrand factor (vWF) is unusually large and similar to the vWF in patients with thrombotic thrombocytopenic purpura. Br J Haematol. 1989;72:68–72.PubMedGoogle Scholar
  24. 24.
    Israels SJ, McMillan-Ward E. Neonatal platelet procoagulant activity. Blood. 2002;100.Google Scholar
  25. 25.
    Michelson AD, Rajasekhar D, Bednarek FJ, Barnard MR. Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults. Thromb Haemost. 2000;84:689–694.PubMedGoogle Scholar
  26. 26.
    Schwarz HP, Muntean W, Watzke H, Richter B, Griffin JH. Low total protein S antigen but high protein S activity due to decreased C4b-binding protein in neonates. Blood. 1988;71:562–565.PubMedGoogle Scholar
  27. 27.
    Monagle P, Chan AK, Albisetti M, Vegh P, Andrew M, Mitchell L. Fibrinolytic system in adolescents: response to venous occlusion stress tests. Pediatr Res. 2003;53:333–337.PubMedGoogle Scholar
  28. 28.
    Allen GA, Wolberg AS, Oliver JA, Hoffman M, Roberts HR, Monroe DM. Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system. J Thromb Haemost. 2004;2:402–413.PubMedGoogle Scholar
  29. 29.
    Butenas S, van't Veer C, Mann KG. “Normal” thrombin generation. Blood. 1999;94:2169–2178.PubMedGoogle Scholar
  30. 30.
    Andrew M, Schmidt B, Mitchell L, Paes B, Ofosu F. Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin. Thromb Haemost. 1990;63:27–30.PubMedGoogle Scholar
  31. 31.
    Cvirn G, Gallistl S, Muntean W. Effects of alpha(2)-macroglobulin and antithrombin on thrombin generation and inhibition in cord and adult plasma. Thromb Res. 2001;101:183–191.PubMedGoogle Scholar
  32. 32.
    Schmidt B, Mitchell L, Ofosu FA, Andrew M. Alpha-2-macroglobulin is an important progressive inhibitor of thrombin in neonatal and infant plasma. Thromb Haemost. 1989;62:1074–1077.PubMedGoogle Scholar
  33. 33.
    Gordon SG, Cross BA. A factor X-activating cysteine protease from malignant tissue. J Clin Invest. 1981;67:1665–1671.PubMedGoogle Scholar
  34. 34.
    Olas B, Wachowicz B, Mielicki WP. Cancer procoagulant and blood platelet activation. Cancer Lett. 2001;169:165–171.PubMedGoogle Scholar
  35. 35.
    Pineo GF, Regoeczi E, Hatton MW, Brain MC. The activation of coagulation by extracts of mucus: a possible pathway of intravascular coagulation accompanying adenocarcinomas. J Lab Clin Med. 1973;82:255–266.PubMedGoogle Scholar
  36. 36.
    VanDeWater L, Tracy PB, Aronson D, Mann KG, Dvorak HF. Tumor cell generation of thrombin via functional prothrombinase assembly. Cancer Res. 1985;45:5521–5525.PubMedGoogle Scholar
  37. 37.
    Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266.PubMedGoogle Scholar
  38. 38.
    Kwaan HC. The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev. 1992;11:291–311.PubMedGoogle Scholar
  39. 39.
    Mignatti P, Rifkin DB. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev. 1993;73:161–195.PubMedGoogle Scholar
  40. 40.
    Giordano P, Del Vecchio GC, Santoro N, et al. Thrombin generation in children with acute lymphoblastic leukemia: effect of leukemia immunophenotypic subgroups. Pediatr Hematol Oncol. 2000;17:667–672.PubMedGoogle Scholar
  41. 41.
    Mitchell L, Hoogendoorn H, Giles AR, Vegh P, Andrew M. Increased endogenous thrombin generation in children with acute lymphoblastic leukemia: risk of thrombotic complications in L-asparaginase-induced antithrombin III deficiency. Blood. 1994;83:386–391.PubMedGoogle Scholar
  42. 42.
    Oner AF, Gurgey A, Kirazli S, Okur H, Tunc B. Changes of hemostatic factors in children with acute lymphoblastic leukemia receiving combined chemotherapy including high dose methylprednisolone and L-asparaginase. Leuk Lymphoma. 1999;33:361–364.PubMedGoogle Scholar
  43. 43.
    Rodeghiero F, Castaman G, Dini E. Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation. Thromb Res. 1990;57:31–38.PubMedGoogle Scholar
  44. 44.
    Mitchell LG, Halton JM, Vegh PA, et al. Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia. Am J Pediatr Hematol Oncol. 1994;16:120–126.PubMedGoogle Scholar
  45. 45.
    Abshire TC, Gold SH, Odom LF, Carson SD, Hathaway WE. The coagulopathy of childhood leukemia. Thrombin activation or primary fibrinolysis? Cancer. 1990;66:716–721.PubMedGoogle Scholar
  46. 46.
    Semeraro N, Montemurro P, Giordano P, Santoro N, De Mattia D, Colucci M. Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma. Thromb Haemost. 1994;72:54–57.PubMedGoogle Scholar
  47. 47.
    Knofler R, Siegert E, Lauterbach I, et al. Clinical importance of prothrombotic risk factors in pediatric patients with malignancy – impact of central venous lines. Eur J Pediatr. 1999;158 Suppl 3:S147–150.PubMedGoogle Scholar
  48. 48.
    Mauz-Korholz C, Junker R, Gobel U, Nowak-Gottl U. Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase (COALL-92 and 97 protocols). Thromb Haemost. 2000;83:840–843.PubMedGoogle Scholar
  49. 49.
    Mitchell L, Andrew M, Hanna K, et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving L-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost. 2003;90:235–244.PubMedGoogle Scholar
  50. 50.
    Nowak-Gottl U, Wermes C, Junker R, et al. Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. Blood. 1999;93:1595–1599.PubMedGoogle Scholar
  51. 51.
    Wermes C, von Depka Prondzinski M, Lichtinghagen R, Barthels M, Welte K, Sykora KW. Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters. Eur J Pediatr. 1999;158 Suppl 3:S143–146.PubMedGoogle Scholar
  52. 52.
    Gregory MA, Hadley GP. The evolution of biofilms in venous access devices implanted in children with Wilms' tumour. Pediatr Surg Int. 1998;13:400–405.PubMedGoogle Scholar
  53. 53.
    Passerini L, Lam K, Costerton JW, King EG. Biofilms on indwelling vascular catheters. Crit Care Med. 1992;20:665–673.PubMedGoogle Scholar
  54. 54.
    Krafte-Jacobs B, Sivit CJ, Mejia R, Pollack MM. Catheter-related thrombosis in critically ill children: comparison of catheters with and without heparin bonding. J Pediatr. 1995;126:50–54.PubMedGoogle Scholar
  55. 55.
    Pierce CM, Wade A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children. Intensive Care Med. 2000;26:967–972.PubMedGoogle Scholar
  56. 56.
    Du YJ, Brash JL, McClung G, Berry LR, Klement P, Chan AK. Protein adsorption on polyurethane catheters modified with a novel antithrombin-heparin covalent complex. J Biomed Mater Res A. 2007;80:216–225.PubMedGoogle Scholar
  57. 57.
    Journeycake JM, Buchanan GR. Catheter-related deep venous thrombosis and other catheter complications in children with cancer. J Clin Oncol. 2006;24:4575–4580.PubMedGoogle Scholar
  58. 58.
    Fratino G, Molinari AC, Parodi S, et al. Central venous catheter-related complications in children with oncological/hematological diseases: an observational study of 418 devices. Ann Oncol. 2005;16:648–654.PubMedGoogle Scholar
  59. 59.
    Male C, Chait P, Andrew M, Hanna K, Julian J, Mitchell L. Central venous line-related thrombosis in children: association with central venous line location and insertion technique. Blood. 2003;101:4273–4278.PubMedGoogle Scholar
  60. 60.
    McLean TW, Fisher CJ, Snively BM, Chauvenet AR. Central venous lines in children with lesser risk acute lymphoblastic leukemia: optimal type and timing of placement. J Clin Oncol. 2005;23:3024–3029.PubMedGoogle Scholar
  61. 61.
    Massicotte MP, Dix D, Monagle P, Adams M, Andrew M. Central venous catheter related thrombosis in children: analysis of the Canadian Registry of Venous Thromboembolic Complications. J Pediatr. 1998;133:770–776.PubMedGoogle Scholar
  62. 62.
    Kuhle S, Koloshuk B, Marzinotto V, et al. A cross-sectional study evaluating post-thrombotic syndrome in children. Thromb Res. 2003;111:227–233.PubMedGoogle Scholar
  63. 63.
    Ruud E, Holmstrom H, Hopp E, Wesenberg F. Central line-associated venous late effects in children without prior history of thrombosis. Acta Paediatr. 2006;95:1060–1065.PubMedGoogle Scholar
  64. 64.
    Athale UH, Chan AK. Thrombosis in children with acute lymphoblastic leukemia. Part II. Pathogenesis of thrombosis in children with acute lymphoblastic leukemia: effects of the disease and therapy. Thromb Res. 2003;111:199–212.PubMedGoogle Scholar
  65. 65.
    Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res. 2006;118:555–568.PubMedGoogle Scholar
  66. 66.
    Lee AY, Levine MN. The thrombophilic state induced by therapeutic agents in the cancer patient. Semin Thromb Hemost. 1999;25:137–145.PubMedGoogle Scholar
  67. 67.
    Priest JR, Ramsay NK, Bennett AJ, Krivit W, Edson JR. The effect of L-asparaginase on antithrombin, plasminogen, and plasma coagulation during therapy for acute lymphoblastic leukemia. J Pediatr. 1982;100:990–995.PubMedGoogle Scholar
  68. 68.
    Togna GI, Togna AR, Franconi M, Caprino L. Cisplatin triggers platelet activation. Thromb Res. 2000;99:503–509.PubMedGoogle Scholar
  69. 69.
    Broome JD. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J Exp Med. 1963;118:99–120.PubMedGoogle Scholar
  70. 70.
    Conard J, Durand G, Feger J, Samama M. Acquired abnormal antithrombin III in L-asparaginase treated patients? IVth International Congress on Thrombosis and Haemostasis. Vienna; 1973:193.Google Scholar
  71. 71.
    Land VJ, Sutow WW, Fernbach DJ, Lane DM, Williams TE. Toxicity of L-asparginase in children with advanced leukemia. Cancer. 1972;30:339–347.PubMedGoogle Scholar
  72. 72.
    Priest JR, Ramsay NK, Latchaw RE, et al. Thrombotic and hemorrhagic strokes complicating early therapy for childhood acute lymphoblastic leukemia. Cancer. 1980;46:1548–1554.PubMedGoogle Scholar
  73. 73.
    Priest JR, Ramsay NK, Steinherz PG, et al. A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia. J Pediatr. 1982;100:984–989.PubMedGoogle Scholar
  74. 74.
    Homans AC, Rybak ME, Baglini RL, Tiarks C, Steiner ME, Forman EN. Effect of L-asparaginase administration on coagulation and platelet function in children with leukemia. J Clin Oncol. 1987;5:811–817.PubMedGoogle Scholar
  75. 75.
    Pui CH, Jackson CW, Chesney C, et al. Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine. J Clin Oncol. 1983;1:380–385.PubMedGoogle Scholar
  76. 76.
    Ruud E, Holmstrom H, de Lange C, Natvig S, Albertsen BK, Wesenberg F. Thrombotic effects of asparaginase in two acute lymphoblastic leukemia protocols (NOPHO ALL-1992 versus NOPHO ALL-2000): a single-institution study. Pediatr Hematol Oncol. 2006;23:207–216.PubMedGoogle Scholar
  77. 77.
    Bushman JE, Palmieri D, Whinna HC, Church FC. Insight into the mechanism of asparaginase-induced depletion of antithrombin III in treatment of childhood acute lymphoblastic leukemia. Leuk Res. 2000;24:559–565.PubMedGoogle Scholar
  78. 78.
    Jaime-Perez JC, Gomez-Almaguer D. Platelet aggregation is stimulated by L-asparginase in children with acute lymphoblastic leukemia and normal individuals. Haematologica. 2002;87:891–892.PubMedGoogle Scholar
  79. 79.
    Isacson S. Effect of prednisolone on the coagulation and fibrinolytic systems. Scand J Haematol. 1970;7:212–216.PubMedGoogle Scholar
  80. 80.
    Ozsoylu S, Strauss HS, Diamond LK. Effects of corticosteroids on coagulation of the blood. Nature. 1962;195:1214–1215.PubMedGoogle Scholar
  81. 81.
    Ozturk G, Ozsoylu S, Gursel T. Effects of methylprednisolone on FVIII:C and vWF levels. Eur J Haematol. 1994;53:119–120.PubMedGoogle Scholar
  82. 82.
    Patrassi GM, Dal Bo Zanon R, Boscaro M, Martinelli S, Girolami A. Further studies on the hypercoagulable state of patients with Cushing's syndrome. Thromb Haemost. 1985;54:518–520.PubMedGoogle Scholar
  83. 83.
    Patrassi GM, Sartori MT, Livi U, et al. Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation. Transplantation. 1997;64:1610–1614.PubMedGoogle Scholar
  84. 84.
    Patrassi GM, Sartori MT, Rigotti P, et al. Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment. Transplantation. 1995;59:1416–1420.PubMedGoogle Scholar
  85. 85.
    Patrassi GM, Sartori MT, Viero ML, Scarano L, Boscaro M, Girolami A. The fibrinolytic potential in patients with Cushing's disease: a clue to their hypercoagulable state. Blood Coagul Fibrinolysis. 1992;3:789–793.PubMedGoogle Scholar
  86. 86.
    Sartori MT, Patrassi GM, Rigotti P, et al. Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients. Transplantation. 2000;69:2116–2121.PubMedGoogle Scholar
  87. 87.
    Sartori MT, Rigotti P, Marchini F, et al. Plasma fibrinolytic capacity in renal transplant recipients: effect of steroid-free immunosuppression therapy. Transplantation. 2003;75:994–998.PubMedGoogle Scholar
  88. 88.
    Sartori TM, Maurizio PG, Sara P, et al. Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation. J Heart Lung Transplant. 1999;18:693–700.PubMedGoogle Scholar
  89. 89.
    van Giezen JJ, Jansen JW. Inhibition of fibrinolytic activity in-vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation. Thromb Haemost. 1992;68:69–73.PubMedGoogle Scholar
  90. 90.
    Nowak-Gottl U, Heinecke A, von Kries R, Nurnberger W, Munchow N, Junker R. Thrombotic events revisited in children with acute lymphoblastic leukemia: impact of concomitant Escherichia coli asparaginase/prednisone administration. Thromb Res. 2001;103:165–172.PubMedGoogle Scholar
  91. 91.
    Nowak-Gottl U, Ahlke E, Fleischhack G, et al. Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration. Blood. 2003;101:2529–2533.PubMedGoogle Scholar
  92. 92.
    Mewhort-Buist TA, Liaw PC, Patel S, Atkinson HM, Berry LR, Chan AK. Treatment of endothelium with the chemotherapy agent vincristine affects activated protein C generation to a greater degree in newborn plasma than in adult plasma. Thromb Res. 2008;122:418–426.PubMedGoogle Scholar
  93. 93.
    Monagle P, Chalmers E, Chan A, et al. Antithrombotic therapy in neonates and children: American college of chest physicians evidencebased clinical practice guidelines (8th Edition). Chest. 2008;133:887S–968S.PubMedGoogle Scholar
  94. 94.
    Ruud E, Holmstrom H, De Lange C, Hogstad EM, Wesenberg F. Low-dose warfarin for the prevention of central line-associated thromboses in children with malignancies--a randomized, controlled study. Acta Paediatr. 2006;95:1053–1059.PubMedGoogle Scholar
  95. 95.
    Meister B, Kropshofer G, Klein-Franke A, Strasak AM, Hager J, Streif W. Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50:298–303.PubMedGoogle Scholar
  96. 96.
    Massicotte P, Julian JA, Gent M, et al. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial. Thromb Res. 2003;109:85–92.PubMedGoogle Scholar
  97. 97.
    Andrew M, Marzinotto V, Massicotte P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res. 1994;35:78–83.PubMedGoogle Scholar
  98. 98.
    McDonald MM, Jacobson LJ, Hay WW Jr, Hathaway WE. Heparin clearance in the newborn. Pediatr Res. 1981;15:1015–1018.PubMedGoogle Scholar
  99. 99.
    Massicotte P, Adams M, Marzinotto V, Brooker LA, Andrew M. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr. 1996;128:313–318.PubMedGoogle Scholar
  100. 100.
    Streif W, Andrew M, Marzinotto V, et al. Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients. Blood. 1999;94:3007–3014.PubMedGoogle Scholar
  101. 101.
    Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost. 1992;68:325–330.PubMedGoogle Scholar
  102. 102.
    Albisetti M. Thrombolytic therapy in children. Thromb Res. 2006;118:95–105.PubMedGoogle Scholar
  103. 103.
    Leaker M, Massicotte MP, Brooker LA, Andrew M. Thrombolytic therapy in pediatric patients: a comprehensive review of the literature. Thromb Haemost. 1996;76:132–134.PubMedGoogle Scholar
  104. 104.
    Zenz W, Arlt F, Sodia S, Berghold A. Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the literature of the last thirty years. Semin Thromb Hemost. 1997;23:321–332.PubMedGoogle Scholar
  105. 105.
    Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood. 2007;110:45–53.PubMedGoogle Scholar
  106. 106.
    Zenz W, Muntean W, Beitzke A, Zobel G, Riccabona M, Gamillscheg A. Tissue plasminogen activator (alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children. Br Heart J. 1993;70:382–385.PubMedGoogle Scholar
  107. 107.
    Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res. 2001;102:V215–224.PubMedGoogle Scholar
  108. 108.
    Monagle P, Adams M, Mahoney M, et al. Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res. 2000;47:763–766.PubMedGoogle Scholar
  109. 109.
    Andrew M. Developmental hemostasis: relevance to hemostatic problems during childhood. Semin Thromb Hemost. 1995;21:341–356.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Feinberg School of Medicine, Children’s Memorial Hospital, Northwestern UniversityChicagoUSA
  2. 2.Division of Hematology/OncologyChildren’s Memorial HospitalChicago

Personalised recommendations