Download PDF
Thromb Haemost 2014; 111(06): 1015-1021
DOI: 10.1160/TH13-10-0827
Review Article
Schattauer GmbH

Epidemiology of venous thrombosis in children with cancer

Dana Piovesan
1   Murdoch Childrens Research Institute, Royal Children’s Hospital, Victoria, Australia
,
Chantal Attard
1   Murdoch Childrens Research Institute, Royal Children’s Hospital, Victoria, Australia
2   Department of Paediatrics, The University of Melbourne, Royal Children’s Hospital, Victoria, Australia
,
Paul Monagle
1   Murdoch Childrens Research Institute, Royal Children’s Hospital, Victoria, Australia
2   Department of Paediatrics, The University of Melbourne, Royal Children’s Hospital, Victoria, Australia
3   Department of Clinical Haematology, Royal Children’s Hospital, Victoria, Australia
,
Vera Ignjatovic
1   Murdoch Childrens Research Institute, Royal Children’s Hospital, Victoria, Australia
2   Department of Paediatrics, The University of Melbourne, Royal Children’s Hospital, Victoria, Australia
› Author Affiliations
Further Information

Publication History

Received: 08 October 2013

Accepted after major revision: 12 January 2014

Publication Date:
02 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

There has been an extensive body of research focusing on the epidemiology of thrombosis in adult cancer populations; however, there is significantly less knowledge about thrombosis in paediatric cancer populations. Thrombosis is diagnosed with increasing frequency in children being treated for cancer, and there is an urgent need to increase our understanding of the epidemiology of thrombosis in this population. Currently, there are no guidelines for identification of high-risk groups, prophylaxis or management of thrombotic complications in paediatric cancer patients. We reviewed the available literature regarding the epidemiology, mechanisms, risk factors, prophylaxis and outcomes of thrombosis in children with cancer and identified areas that require further research. The reported incidence of symptomatic venous thromboembolism (VTE) in children with cancer ranges between 2.1% and 16%, while the incidence of asymptomatic events is approximately 40%. Approximately 30% of VTE in this population is associated with central venous lines (CVL). The most common location of VTE is upper and lower extremity deep venous thrombosis (43 to 50% of events, respectively), while 50% of events in ALL patients occur in the central nervous system. Key characteristics that increase the risk of thrombosis include the type of cancer, age of the patient, the presence of a CVL, presence of pulmonary/intra thoracic disease, as well as the type of chemotherapy. Outcomes for paediatric cancer patients with VTE include post-thrombotic syndrome, pulmonary embolism, recurrent thromboembolism, destruction of upper venous system and death. Prospective studies aimed at enabling risk stratification of patients are required to facilitate development of paediatric specific recommendations related to thromboprophylaxis in this population.

Keywords

Cancer - child - epidemiology - incidence - thrombosis - paediatrics
 

  • References

  • 1 Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer 2010; 102 (Suppl. 01) S2-9.
    CrossrefPubMedSearch in Google Scholar
  • 2 Andrew M. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994; 83: 1251-1257.
    CrossrefPubMedSearch in Google Scholar
  • 3 Sandoval JA. et al. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg 2008; 47: 837-843.
    CrossrefPubMedSearch in Google Scholar
  • 4 van Ommen CH. et al. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr 2001; 139: 676-681.
    CrossrefPubMedSearch in Google Scholar
  • 5 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995; 96: 939-943.
    CrossrefPubMedSearch in Google Scholar
  • 6 O’Brien SH. et al. Venous thromboembolism and adolescent and young adult oncology inpatients in US children’s hospitals, 2001 to 2008. J Pediatr 2011; 159: 133-137.
    CrossrefPubMedSearch in Google Scholar
  • 7 Lipay NV. et al. Epidemiology of venous thromboembolism in children with malignant diseases: a single-center study of the Belarusian Center for Pediatric Oncology and Hematology. Thromb Res 2011; 128: 130-134.
    CrossrefPubMedSearch in Google Scholar
  • 8 Athale U. et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer 2008; 51: 792-797.
    CrossrefPubMedSearch in Google Scholar
  • 9 Halton J. et al. Do children with central venous line (CVL) dysfunction have increased risk of symptomatic thromboembolism compared to those without CVL-dysfunction, while on cancer therapy?. BMC Cancer 2012; 12: 314.
    CrossrefPubMedSearch in Google Scholar
  • 10 Massicotte MP. et al. Central venous catheter related thrombosis in children: analysis of the Canadian Registry of Venous Thromboembolic Complications. J Pediatr 1998; 133: 770-776.
    CrossrefPubMedSearch in Google Scholar
  • 11 Deitcher SR. et al. Clinically evident venous thromboembolic events in children with brain tumors. J Pediatr 2004; 145: 848-850.
    CrossrefPubMedSearch in Google Scholar
  • 12 Wiernikowski JT, Athale UH. Thromboembolic complications in children with cancer. Thromb Res 2006; 118: 137-152.
    CrossrefPubMedSearch in Google Scholar
  • 13 Mitchell LG. 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.
    CrossrefPubMedSearch in Google Scholar
  • 14 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.
    CrossrefPubMedSearch in Google Scholar
  • 15 Wermes C. et al. Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters. Eur J Pediatr 1999; 158 (Suppl. 03) S143-146.
    CrossrefPubMedSearch in Google Scholar
  • 16 Caruso V. 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.
    CrossrefPubMedSearch in Google Scholar
  • 17 Athale UH, Chan AK. Thromboembolic complications in pediatric hematologic malignancies. Semin Thromb Hemost 2007; 33: 416-426.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Athale UH. et al. Thromboembolism in children with lymphoma. Thromb Res 2008; 122: 459-465.
    CrossrefPubMedSearch in Google Scholar
  • 19 Ruggiero A. et al. Groshong catheter-related complications in children with cancer. Pediatr Blood Cancer 2010; 54: 947-951.
    CrossrefPubMedSearch in Google Scholar
  • 20 Schiavetti A. et al. Venous thrombosis in children with solid tumors. J Pediatr Hematol Oncol 2008; 30: 148-152.
    CrossrefPubMedSearch in Google Scholar
  • 21 Athale U. et al. Thromboembolism in children with sarcoma. Pediatr Blood Cancer 2007; 49: 171-176.
    CrossrefPubMedSearch in Google Scholar
  • 22 Knofler R. et al. Clinical importance of prothrombotic risk factors in pediatric patients with malignancy--impact of central venous lines. Eur J Pediatr 1999; 158 (Suppl. 03) S147-150.
    CrossrefPubMedSearch in Google Scholar
  • 23 Revel-Vilk S. et al. Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer. Cancer 2010; 116: 4197-4205.
    CrossrefPubMedSearch in Google Scholar
  • 24 Glaser DW. et al. Catheter-related thrombosis in children with cancer. J Pediatr 2001; 138: 255-259.
    CrossrefPubMedSearch in Google Scholar
  • 25 Journeycake JM, Buchanan GR. Catheter-related deep venous thrombosis and other catheter complications in children with cancer. J Clin Oncol 2006; 24: 4575-4580.
    CrossrefPubMedSearch in Google Scholar
  • 26 Appel IM. et al. L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia. Thromb Haemost 2008; 100: 330-337.
    Thieme ConnectPubMedSearch in Google Scholar
  • 27 Al-Aridi C. et al. Thrombosis in children with acute lymphoblastic leukemia treated at a tertiary care center in Lebanon: revisiting the role of predictive models. Pediatr Hematol Oncol 2011; 28: 676-681.
    CrossrefPubMedSearch in Google Scholar
  • 28 Giordano P. et al. Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. Am J Hematol 2010; 85: 325-330.
    PubMedSearch in Google Scholar
  • 29 Mitchell L. et al. 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.
    CrossrefPubMedSearch in Google Scholar
  • 30 Nowak-Gottl U. et al. Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment. Best Pract Res Clin Haematol 2009; 22: 103-114.
    CrossrefPubMedSearch in Google Scholar
  • 31 Stanley A, Young A. Primary prevention of venous thromboembolism in medical and surgical oncology patients. Br J Cancer 2010; 102 (Suppl. 01) S10-16.
    CrossrefPubMedSearch in Google Scholar
  • 32 Ruud E. et al. Prevalence of thrombophilia and central venous catheter-associated neck vein thrombosis in 41 children with cancer--a prospective study. Med Pediatr Oncol 2002; 38: 405-410.
    CrossrefPubMedSearch in Google Scholar
  • 33 Stiakaki E. et al. Prevalence of Factor V Leiden and other thrombophilic traits among Cretan children with malignancy. Pediatr Blood Cancer 2005; 44: 386-389.
    CrossrefPubMedSearch in Google Scholar
  • 34 Nowak-Gottl U. 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.
    CrossrefPubMedSearch in Google Scholar
  • 35 Harlev D. et al. Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. Thromb Res 2010; 126: 93-97.
    CrossrefPubMedSearch in Google Scholar
  • 36 Mauz-Korholz C. et al. 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.
    PubMedSearch in Google Scholar
  • 37 Elhasid R. et al. Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia. Blood Coagul Fibrinolysis 2001; 12: 367-370.
    CrossrefPubMedSearch in Google Scholar
  • 38 Mitchell LG. et al. Hemostasis in childhood acute lymphoblastic leukemia: coagulopathy induced by disease and treatment. Semin Thromb Hemost 1995; 21: 390-401.
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Male C. et al. Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase. Thromb Haemost 2002; 87: 593-598.
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Massicotte P. 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.
    CrossrefPubMedSearch in Google Scholar
  • 41 Nowak-Gottl U. et al. Intraoperative clotting factor dilution and activated hemostasis in children with Ewing’s sarcoma or osteosarcoma: a prospective longitudinal study. Haematologica 1995; 80: 311-317.
    PubMedSearch in Google Scholar
  • 42 Silverman LB. et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001; 97: 1211-1218.
    CrossrefPubMedSearch in Google Scholar