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Semin Thromb Hemost 2007; 33(4): 416-426
DOI: 10.1055/s-2007-976177
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Thromboembolic Complications in Pediatric Hematologic Malignancies

Uma H. Athale1 , Anthony K.C Chan1 , 2
  • 1Division of Pediatric Hematology/Oncology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  • 2Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
Further Information

Publication History

Publication Date:
24 May 2007 (online)

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ABSTRACT

Thromboembolism (TE) is an uncommon entity in childhood. Overall 25% of children with thrombosis and more than 40% of children with central venous line (CVL) -related TE enrolled on the Canadian Pediatric Thrombophilia Registry had underlying diagnosis of cancer. However, so far there are very little data describing the epidemiology of TE in children with cancer. Most of the available information in this area originates mainly from retrospective and some prospective observational cohort studies conducted in children with acute lymphoblastic leukemia (ALL). Although ALL has been the most common cancer reported in association with thrombosis in children, available data from small studies indicate that TE is equally common in children with acute myeloid leukemia and lymphoma. TE in association with leukemia and lymphoma seems to be a multifactorial entity. Potential risk factors include increased thrombin generation related to leukemia, age of the patients, use of CVL, chemotherapy including asparaginase and corticosteroids, infections, and inherited prothrombotic state. Management of TE in a child with cancer presents a unique challenge in terms of balancing risk versus benefit. Conservative therapy could lead to clot extension and risks of additional morbidity or mortality; however, chemotherapy-related thrombocytopenia and coagulopathy increase the risk of bleeding complications. In summary, TE is a frequent and serious complication in children with hematologic malignancies. More prospective studies are required to define the epidemiology, pathogenesis, and management of TE in children with hematologic malignancies.

KEYWORDS

Pediatrics - leukemia - lymphoma - thromboembolism - central venous catheter

REFERENCES

  • 1 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
  • 2 Nowak-Gottl U, Kosch A, Schlegel N. Thromboembolism in newborns, infants and children.  Thromb Haemost. 2001;  86 464-474
    PubMedGoogle Scholar
  • 3 Monagle P, Chan A, Massicotte P, Chalmers E, Michelson A D. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 645S-687S
    CrossrefPubMedGoogle Scholar
  • 4 van Ommen C, Heijboer H, Baller H, Hirasing R, Heijmano H, Peter M. Venous thromboembolism in childhood: a prospective two-year registry in the Netherlands.  J Pediatr. 2001;  139 676-681
    CrossrefPubMedGoogle Scholar
  • 5 Sutor A H, Chan A K, Massicotte P. Low-molecular-weight heparin in pediatric patients.  Semin Thromb Hemost. 2004;  30(suppl 1) 31-39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Newall F, Wallace T, Crock C et al.. Venous thromboembolic disease: a single-centre case series study.  J Paediatr Child Health. 2006;  42 803-807
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Massicotte M P, 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
    CrossrefPubMedGoogle Scholar
  • 9 Athale U H, Chan A K. Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of thrombosis in children with acute lymphoblastic leukemia.  Thromb Res. 2003;  111 125-131
    CrossrefPubMedGoogle Scholar
  • 10 Athale U H, Chan A K. 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
    CrossrefPubMedGoogle Scholar
  • 11 Athale U H, Chan A K. Thrombosis in children with acute lymphoblastic leukemia. Part III. Pathogenesis of thrombosis in children with acute lymphoblastic leukemia: effects of host environment.  Thromb Res. 2003;  111 321-327
    CrossrefPubMedGoogle Scholar
  • 12 Mitchell L G, Sutor A H, Andrew M. Hemostasis in childhood acute lymphoblastic leukemia: coagulopathy induced by disease and treatment.  Semin Thromb Hemost. 1995;  21 390-401
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Ruud E, Holmstrom H, De Lange C, Hogstad E M, 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
    CrossrefPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 Unal S, Varan A, Yalcin B, Buyukpamukcu M, Gurgey A. Evaluation of thrombotic children with malignancy.  Ann Hematol. 2005;  84 395-399
    CrossrefPubMedGoogle Scholar
  • 16 Wermes C, von Depka Prondzinski M, Lichtinghagen R, Barthels M, Welte K, Sykora K W. Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters.  Eur J Pediatr. 1999;  158(suppl 3) S143-S146
    CrossrefPubMedGoogle Scholar
  • 17 Glaser D W, Medeiros D, Rollins N, Buchanan G R. Catheter-related thrombosis in children with cancer.  J Pediatr. 2001;  138 255-259
    CrossrefPubMedGoogle Scholar
  • 18 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) 147-150
    CrossrefPubMedGoogle Scholar
  • 19 Journeycake J M, Buchanan G R. Catheter-related deep venous thrombosis and other catheter complications in children with cancer.  J Clin Oncol. 2006;  24 4575-4580
    CrossrefPubMedGoogle Scholar
  • 20 Mitchell L, Hoogendoorn H, Giles A R, 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
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Abshire T C, Gold S H, Odom L F, Carson S D, Hathaway W E. The coagulopathy of childhood leukemia. Thrombin activation or primary fibrinolysis?.  Cancer. 1990;  66 716-721
    CrossrefPubMedGoogle Scholar
  • 23 Oner A F, 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
  • 24 Giordano P, Del Vecchio G C, Santoro N et al.. Thrombin generation in children with acute lymphoblastic leukemia: effect of leukemia immunophenotypic subgroups.  Pediatr Hematol Oncol. 2000;  17 667-672
    CrossrefPubMedGoogle Scholar
  • 25 Uszynski M, Osinska M, Zekanowska E, Ziolkowska E. Children with acute lymphoblastic leukemia: is there any subgroup of children without elevated thrombin generation? A preliminary study utilizing measurements of thrombin-antithrombin III complexes.  Med Sci Monit. 2000;  6 108-111
    PubMedGoogle Scholar
  • 26 Sifontes M T, Nuss R, Hunger S P, Wilimas J, Jacobson L J, Manco-Johnson M J. The factor V Leiden mutation in children with cancer and thrombosis.  Br J Haematol. 1997;  96 484-489
    CrossrefPubMedGoogle Scholar
  • 27 Athale U H, Siciliano S A, Crowther M, Barr R D, Chan A K. Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of disease.  Br J Haematol. 2005;  129 803-810
    CrossrefPubMedGoogle Scholar
  • 28 Silverman L B, Gelber R D, Dalton V K et al.. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.  Blood. 2001;  97 1211-1218
    CrossrefPubMedGoogle Scholar
  • 29 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
    CrossrefPubMedGoogle Scholar
  • 30 Massicotte P, Mitchell L. Thromboprophylaxis of central venous lines in children with cancer: the first steps taken on the long road ahead.  Acta Paediatr. 2006;  95 1049-1052
    CrossrefPubMedGoogle Scholar
  • 31 Levine M, Kakkar A K. Catheter-associated thrombosis: thromboprophylaxis or not?.  J Clin Oncol. 2005;  23 4006-4008
    CrossrefPubMedGoogle Scholar
  • 32 Verso M, Agnelli G, Bertoglio S et al.. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.  J Clin Oncol. 2005;  23 4057-4062
    CrossrefPubMedGoogle Scholar
  • 33 Caers J, Fontaine C, Vinh-Hung V et al.. Catheter tip position as a risk factor for thrombosis associated with the use of subcutaneous infusion ports.  Support Care Cancer. 2005;  13 325-331
    CrossrefPubMedGoogle Scholar
  • 34 Lee A Y, Levine M N, Butler G et al.. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer.  J Clin Oncol. 2006;  24 1404-1408
    CrossrefPubMedGoogle Scholar
  • 35 Fratino G, Molinari A C, 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
    CrossrefPubMedGoogle Scholar
  • 36 McLean T W, Fisher C J, Snively B M, Chauvenet A R. Central venous lines in children with lesser risk acute lymphoblastic leukemia: optimal type and timing of placement.  J Clin Oncol. 2005;  23 3024-3029
    CrossrefPubMedGoogle Scholar
  • 37 Male C, Julian J A, Massicotte P, Gent M, Mitchell L. Significant association with location of central venous line placement and risk of venous thrombosis in children.  Thromb Haemost. 2005;  94 516-521
    PubMedGoogle Scholar
  • 38 Sutherland D E, Weitz I C, Liebman H A. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment.  Am J Hematol. 2003;  72 43-52
    CrossrefPubMedGoogle Scholar
  • 39 Lee A Y, Levine M N. The thrombophilic state induced by therapeutic agents in the cancer patient.  Semin Thromb Hemost. 1999;  25 137-145
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Haddad T C, Greeno E W. Chemotherapy-induced thrombosis.  Thromb Res. 2006;  118 555-568
    CrossrefPubMedGoogle Scholar
  • 41 Mills P J, Parker B, Jones V et al.. The effects of standard anthracycline-based chemotherapy on soluble ICAM-1 and vascular endothelial growth factor levels in breast cancer.  Clin Cancer Res. 2004;  10 4998-5003
    CrossrefPubMedGoogle Scholar
  • 42 Togna G I, Togna A R, Franconi M, Caprino L. Cisplatin triggers platelet activation.  Thromb Res. 2000;  99 503-509
    CrossrefPubMedGoogle Scholar
  • 43 Walsh J, Wheeler H R, Geczy C L. Modulation of tissue factor on human monocytes by cisplatin and adriamycin.  Br J Haematol. 1992;  81 480-488
    PubMedGoogle Scholar
  • 44 Wang J, Weiss I, Svoboda K, Kwaan H C. Thrombogenic role of cells undergoing apoptosis.  Br J Haematol. 2001;  115 382-391
    CrossrefPubMedGoogle Scholar
  • 45 Morel O, Toti F, Hugel B et al.. Procoagulant microparticles: disrupting the vascular homeostasis equation?.  Arterioscler Thromb Vasc Biol. 2006;  26 2594-2604
    CrossrefPubMedGoogle Scholar
  • 46 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
  • 47 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
  • 48 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
    CrossrefPubMedGoogle Scholar
  • 49 Muller H J, Boos J. Use of L-asparaginase in childhood ALL.  Crit Rev Oncol Hematol. 1998;  28 97-113
    PubMedGoogle Scholar
  • 50 Ozturk G, Ozsoylu S, Gursel T. Effects of methylprednisolone on FVIII:C and vWF levels.  Eur J Haematol. 1994;  53 119-120
    PubMedGoogle Scholar
  • 51 Sartori T M, Maurizio P G, 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
  • 52 Patrassi G M, Sartori M T, Rigotti P et al.. Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment.  Transplantation. 1995;  59 1416-1420
    CrossrefPubMedGoogle Scholar
  • 53 Patrassi G M, 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
  • 54 Patrassi G M, Sartori M T, Viero M L, 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
    CrossrefPubMedGoogle Scholar
  • 55 Sartori M T, Patrassi G M, Rigotti P et al.. Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients.  Transplantation. 2000;  69 2116-2121
    CrossrefPubMedGoogle Scholar
  • 56 Sartori M T, 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
  • 57 Patrassi G M, Sartori M T, Livi U et al.. Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation.  Transplantation. 1997;  64 1610-1614
    PubMedGoogle Scholar
  • 58 van Giezen J J, Jansen J W. Inhibition of fibrinolytic activity in-vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation.  Thromb Haemost. 1992;  68 69-73
    PubMedGoogle Scholar
  • 59 van Giezen J J, Brakkee J G, Dreteler G H, Bouma B N, Jansen J W. Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis.  Blood Coagul Fibrinolysis. 1994;  5 249-255
    PubMedGoogle Scholar
  • 60 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
    CrossrefPubMedGoogle Scholar
  • 61 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
    CrossrefPubMedGoogle Scholar
  • 62 Raad I I, Luna M, Khalil S A, Costerton J W, Lam C, Bodey G P. The relationship between the thrombotic and infectious complications of central venous catheters.  JAMA. 1994;  271 1014-1016
    CrossrefPubMedGoogle Scholar
  • 63 van Rooden C J, Schippers E F, Barge R M et al.. Infectious complications of central venous catheters increase the risk of catheter-related thrombosis in hematology patients: a prospective study.  J Clin Oncol. 2005;  23 2655-2660
    PubMedGoogle Scholar
  • 64 Bick R L. Cancer-associated thrombosis.  N Engl J Med. 2003;  349 109-111
    CrossrefPubMedGoogle Scholar
  • 65 Hack C E. Tissue factor pathway of coagulation in sepsis.  Crit Care Med. 2000;  28 S25-S30
    PubMedGoogle Scholar
  • 66 Esmon C. The protein C pathway.  Crit Care Med. 2000;  28 S44-S48
    CrossrefPubMedGoogle Scholar
  • 67 Elhasid R, Lanir N, Sharon R et al.. Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia.  Blood Coagul Fibrinolysis. 2001;  12 367-370
    CrossrefPubMedGoogle Scholar
  • 68 Kishi S, Griener J, Cheng C et al.. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia.  J Clin Oncol. 2003;  21 3084-3091
    CrossrefPubMedGoogle Scholar
  • 69 Mitchell L G, 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
    CrossrefPubMedGoogle Scholar
  • 70 Ruud E, Holmstrom H, Brosstad F, Wesenberg F. Children with acute lymphoblastic leukaemia have high plasma levels of total homocysteine at time of diagnosis.  Scand J Clin Lab Invest. 2006;  66 67-78
    PubMedGoogle Scholar
  • 71 Stiakaki E, Germanakis I, Sfyridaki C, Katzilakis N, Danilatou V, Kalmanti M. Prevalence of factor V Leiden and other thrombophilic traits among Cretan children with malignancy.  Pediatr Blood Cancer. 2005;  44 386-389
    CrossrefPubMedGoogle Scholar
  • 72 Randolph A G, Cook D J, Gonzales C A, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials.  Chest. 1998;  113 165-171
    CrossrefPubMedGoogle Scholar
  • 73 Couban S, Goodyear M, Burnell M et al.. Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer.  J Clin Oncol. 2005;  23 4063-4069
    CrossrefPubMedGoogle Scholar
  • 74 Agnelli G, Verso M. Is antithrombotic prophylaxis required in cancer patients with central venous catheters? No.  J Thromb Haemost. 2006;  4 14-15
    CrossrefPubMedGoogle Scholar
  • 75 Massicotte P, Julian J A, Gent M et al.. An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial.  Thromb Res. 2003;  109 101-108
    CrossrefPubMedGoogle Scholar
  • 76 Murphy M S, John P R, Mayer A D, Buckels J A, Kelly D A. Heparin therapy and bone fractures.  Lancet. 1992;  340 1098
    PubMedGoogle Scholar
  • 77 Avioli L V. Heparin-induced osteopenia: an appraisal.  Adv Exp Med Biol. 1975;  52 375-387
    PubMedGoogle Scholar
  • 78 Sackler J P, Liu L. Heparin-induced osteoporosis.  Br J Radiol. 1973;  46 548-550
    CrossrefPubMedGoogle Scholar
  • 79 Roebuck D J. Skeletal complications in pediatric oncology patients.  Radiographics. 1999;  19 873-885
    PubMedGoogle Scholar
  • 80 Halton J M, Atkinson S A, Fraher L et al.. Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia.  J Bone Miner Res. 1996;  11 1774-1783
    PubMedGoogle Scholar
  • 81 Arikoski P, Komulainen J, Riikonen P et al.. Impaired development of bone mineral density during chemotherapy: a prospective analysis of 46 children newly diagnosed with cancer.  J Bone Miner Res. 1999;  14 2002-2009
    CrossrefPubMedGoogle Scholar
  • 82 Dolovich L R, Ginsberg J S, Douketis J D, Holbrook A M, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency.  Arch Intern Med. 2000;  160 181-188
    CrossrefPubMedGoogle Scholar
  • 83 van Den Belt A G, Prins M H, Lensing A W et al.. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism.  Cochrane Database Syst Rev. 2000;  CD001100
    PubMedGoogle Scholar
  • 84 Gould M K, Dembitzer A D, Doyle R L, Hastie T J, Garber A M. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.  Ann Intern Med. 1999;  130 800-809
    CrossrefPubMedGoogle Scholar
  • 85 Massicotte P, Adams M, Marzinotto V, Brooker L A, Andrew M. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.  J Pediatr. 1996;  128 313-318
    CrossrefPubMedGoogle Scholar
  • 86 Albisetti M, Andrew M. Low molecular weight heparin in children.  Eur J Pediatr. 2002;  161 71-77
    CrossrefPubMedGoogle Scholar
  • 87 Dix D, Andrew M, Marzinotto V et al.. The use of low molecular weight heparin in pediatric patients: a prospective cohort study.  J Pediatr. 2000;  136 439-445
    CrossrefPubMedGoogle Scholar
  • 88 Nohe N, Flemmer A, Rumler R, Praun M, Auberger K. The low molecular weight heparin dalteparin for prophylaxis and therapy of thrombosis in childhood: a report on 48 cases.  Eur J Pediatr. 1999;  158(suppl 3) S134-S139
    CrossrefPubMedGoogle Scholar
  • 89 Lee A Y, Levine M N, Baker R I et al.. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.  N Engl J Med. 2003;  349 146-153
    CrossrefPubMedGoogle Scholar
  • 90 Massicotte P, Julian J A, 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
    CrossrefPubMedGoogle Scholar
  • 91 Linkins L A, Weitz J I. New anticoagulants.  Semin Thromb Hemost. 2003;  29 619-631
    Article in Thieme ConnectPubMedGoogle Scholar
  • 92 Deitcher S R, Topoulos A P, Bartholomew J R, Kichuk-Chrisant M R. Lepirudin anticoagulation for heparin-induced thrombocytopenia.  J Pediatr. 2002;  140 264-266
    CrossrefPubMedGoogle Scholar
  • 93 Nowak-Gottl U, Rath B, Binder M et al.. Inefficacy of fresh frozen plasma in the treatment of L-asparaginase-induced coagulation factor deficiencies during ALL induction therapy.  Haematologica. 1995;  80 451-453
    PubMedGoogle Scholar
  • 94 Halton J M, Mitchell L G, Vegh P, Eves M, Andrew M E. Fresh frozen plasma has no beneficial effect on the hemostatic system in children receiving L-asparaginase.  Am J Hematol. 1994;  47 157-161
    CrossrefPubMedGoogle Scholar
  • 95 Gugliotta L, D'Angelo A, Mattioli Belmonte M et al.. Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo.  Br J Haematol. 1990;  74 465-470
    PubMedGoogle Scholar
  • 96 Zaunschirm A, Muntean W. Correction of hemostatic imbalances induced by L-asparaginase therapy in children with acute lymphoblastic leukemia.  Pediatr Hematol Oncol. 1986;  3 19-25
    CrossrefPubMedGoogle Scholar
  • 97 Nowak-Gottl U, Kuhn N, Wolff J E et al.. Inhibition of hypercoagulation by antithrombin substitution in E. coli L-asparaginase-treated children.  Eur J Haematol. 1996;  56 35-38
    PubMedGoogle Scholar
  • 98 Wiernikowski J T, Crowther M, Clase C M, Ingram A, Andrew M, Chan A K. Stability and sterility of recombinant tissue plasminogen activator at -30 degrees C.  Lancet. 2000;  355 2221-2222
    CrossrefPubMedGoogle Scholar
  • 99 Choi M, Massicotte M P, Marzinotto V, Chan A K, Holmes J L, Andrew M. The use of alteplase to restore patency of central venous lines in pediatric patients: a cohort study.  J Pediatr. 2001;  139 152-156
    CrossrefPubMedGoogle Scholar
  • 100 Wiernikowski J T, Athale U H. Thromboembolic complications in children with cancer.  Thromb Res. 2006;  118 137-152
    CrossrefPubMedGoogle Scholar
  • 101 Levine M, Gent M, Hirsh J et al.. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.  N Engl J Med. 1996;  334 677-681
    CrossrefPubMedGoogle Scholar
  • 102 Koopman M M, Prandoni P, Piovella F et al.. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group.  N Engl J Med. 1996;  334 682-687
    CrossrefPubMedGoogle Scholar
  • 103 Revel-Vilk S, Chan A K. Anticoagulation therapy in children.  Semin Thromb Hemost. 2003;  29 425-432
    Article in Thieme ConnectPubMedGoogle Scholar
  • 104 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
  • 105 Managle T, Chan A KC, de Veder G, Massicotte M P. Vitamin K antagonist warfarin and acenocoumarol therapy. In: Andrew's Pediatric Thromboembolism and Stroke. 3rd ed. Hamilton, Canada; BC Decker 2006: 104-115
    Google Scholar
  • 106 Buck M L. Anticoagulation with warfarin in infants and children.  Ann Pharmacother. 1996;  30 1316-1322
    PubMedGoogle Scholar

Anthony K.C Chan

3N27D, McMaster University

1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5

Email: akchan@mcmaster.ca

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