Skip to main content
Log in

Evaluation of thrombotic children with malignancy

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The purpose of this study was to evaluate inherited and acquired prothrombotic risk factors among children with malignancies who have thrombosis and emphasize the importance of inherited prothrombotic risk factors. Thirty-seven consecutive children with thrombosis and malignancy were included in this study. The patients were evaluated separately for time of development of thrombosis, insertion of a central venous line (CVL), history of l-asparaginase usage, and recent infections. Prothrombotic risk factors such as factor V G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy. Thrombosis was detected in 9 patients at the time of diagnosis, during maintenance therapy in 25 patients, and after the discontinuation of treatment in 3 patients. One or two additional prothrombotic risk factors other than l-asparaginase therapy and insertion of central venous lines were present in 20 of these patients (54%). It was found that eight patients had the factor V G1691A mutation in the heterozygote state. One of them had the factor V G1691A mutation associated with a history of infection and one patient had the factor V G1691A mutation associated with factor VIII elevation. One had the the prothrombin G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation, two had factor VIII elevation, one had a decreased protein S level, one had a decreased protein C level, one had antiphospholipid positivity, and two had histories of infection. Malignancy is an important risk factor for the development of childhood thrombosis. However, the risk of thrombosis increases when accompanied by additional prothrombotic risk factors. For this reason, especially children with malignancy and at high risk for the development of thrombosis, such as those who have received l-asparaginase or a replaced CVL during their therapy, might be screened for additional prothrombotic risk factors and appropriate measures might be taken to prevent the development of thrombosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sutherland DE, Weitz IC, Liebman HA (2003) Thromboembolic complications of cancer epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol 72:43–52

    Article  PubMed  Google Scholar 

  2. Lee AY, Levine MN (2003) Venous thromboembolism and cancer: risks and outcomes. Circulation 17:117–121

    Google Scholar 

  3. Rodger LB (2003) Thrombosis and thrombophilia: diagnosis and management. Hematol Oncol Clin North Am 17:9–37

    Google Scholar 

  4. Falanga A, Rickles FR (1999) Pathophysiology of the thrombophilic state in the cancer patient. Semin Thromb Hemost 25:173–181

    Google Scholar 

  5. Gouın I, Samama M (1999) Laboratory diagnosis of the thrombophilic state in cancer patients. Semin Thromb Hemost 25:167–172

    Google Scholar 

  6. Bick RL (2003) Cancer-associated thrombosis. N Engl J Med 349:109–111

    Google Scholar 

  7. Bell RW (1996) The fibrinolytic system in neoplasia. Semin Thromb Hemost 22:459–478

    Google Scholar 

  8. Guarini A, Mussoni A, Gugliatta L, Chetti L, Niewiarowski T, Catani L, Macchi S, Donati MB, Tura S (1987) Depressed fibrinolysis in patients with acute leukemia. Br J Haematol 66:327–330

    Google Scholar 

  9. Goldschmidt B, Koos R (1984) Metabolism of fibrinogen in children with acute lymphoblastic leukemia. Eur J Pediatr 143:140–144

    Google Scholar 

  10. Semeraro N, Montemurro P, Giardona P, Schettini F, Santoro N, Mattia D, Giordano D, Ronese M, Colucci M (1990) Unbalanced coagulation fibrinolysis potential during l-asparaginase therapy in children with acute lymphoblastic leukemia. Thromb Haemost 64:38–40

    Google Scholar 

  11. Nowak-Göttl U, Heineche A, Von Kries R, Nürnberger W, Münchow N, Junker R (2001) Thrombotic events revisited in children with acute lymphoblastic leukemia: impact of concomitant Escherichia coli asparaginase/prednisone administration. Thromb Res 103:165–172

    Google Scholar 

  12. Wilimas JA, Hudson M, Rao B, Luo X, Lott L, Kaste SC (1998) Late vascular occlusion of central lines in pediatric malignancies. Pediatrics 101:1–5

    Google Scholar 

  13. Bona DR (1999) Thrombotic complication of central venous catheters in cancer patients. Semin Thromb Hemost 25:147–155

    Google Scholar 

  14. Ehrenforth S, Junker R, Koch HG, Kreuz W, Münchow N, Scharrer I, Nowak-Göttl U (1999) Multicentre evaluation of combined prothrombotic defects associated with thrombophilia in childhood. Eur J Pediatr 158:97–104

    Google Scholar 

  15. Nowak-Göttl U, Wermes C, Junker R, Koch HG, Schobess R, Fleischhack, Schwabe D, Ehrenforth S (1999) Prospective evaluation of the thrombotic risk in children with acute leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. Blood 93:1595–1599

    Google Scholar 

  16. Nowak-Göttl U, Dübbers A, Kececioglu D, Koch GH, Kotthoff S, Runde J, Vielhaber H (1997) Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a prospective study. J Pediatr 131:608–612

    Google Scholar 

  17. Wermes C, Prondzinski D, Lichtinghagen R, Barthels M, Welte K, Sykora KW (1999) Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters. Eur J Pediatr 158:143–146

    Google Scholar 

  18. Knofler R, Siegert E, Lauterbach I, Taut-Sack H, Siegert G, Gehrisch S, Müller D, Rupprecht E, Kabus M (1999) Clinical importance of prothrombotic risk factors in pediatric patients with malignancy—impact of central venous lines. Eur J Pediatr 158 [Suppl 3]:S147–S150

    Google Scholar 

  19. Sifontes MT, Nuss R, Hunger SP, Williams J, Jacobson LS, Manco-Johnson MJ (1997) The factor V Leiden mutation in children with cancer and thrombosis. Br J Haematol 96:484–498

    Google Scholar 

  20. Gurgey A, Buyukpamukcu M, Baykurt C, Yalcın B, Gogus S (1997) Portal vein thrombosis in association with factor V Leiden mutation in a patient with hepatocellular carcinoma. Med Pediatr Oncol 56:189–190

    Google Scholar 

  21. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67

    Article  CAS  PubMed  Google Scholar 

  22. Poort SR, Rosendaal FR, Reistma PH, Bertina RM (1996) A common genetic variation in the 3-prime-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703

    CAS  PubMed  Google Scholar 

  23. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343:1846–1850

    Article  CAS  PubMed  Google Scholar 

  24. Gurgey A, Mesci L (1997) The prevalence of factor V Leiden (1691 G–A) mutation in Turkey. Turk J Pediatr 39:313–315

    Google Scholar 

  25. Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D et al (1994) Venous thromboembolic complications (VTE) in children: first analyses of the Canadian registry of VTE. Blood 83:1251–1257

    CAS  PubMed  Google Scholar 

  26. Nowak-Göttl U, Junker R, Hartmaier H, Koch HG, Münchow N, Assmann G, Von Eckardstein A (1999) Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. Circulation 100:743–748

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aytemiz Gürgey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ünal, S., Varan, A., Yalçın, B. et al. Evaluation of thrombotic children with malignancy. Ann Hematol 84, 395–399 (2005). https://doi.org/10.1007/s00277-005-1004-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-005-1004-x

Keywords

Navigation