Skip to main content
SpringerLink
Log in

The importance of cardiovascular risk factors for thrombosis prediction in patients with essential thrombocythemia

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The current widely accepted stratification defined by age and previous thrombosis in patients with essential thrombocythemia (ET) probably deserves deeper analysis. The aim of our study was to identify additional factors at the time of diagnosis, which have an impact on the thrombosis prediction. We conducted a study of 244 consecutive ET patients with median follow-up of 83 months. We analyzed the influence of age, gender, laboratory parameters, history of previous thrombosis, spleen size, JAK2 mutation as well as cardiovascular (CV) risk factors including arterial hypertension, diabetes, active tobacco use and hyperlipidemia in the terms of thrombosis. The most important predictors of thrombosis in multivariate Cox regression model were the presence of CV risk factors (p = 0.004) and previous thrombosis (p = 0.038). Accordingly, we assigned risk scores based on multivariable analysis–derived hazard ratios (HR) to the presence of 1 CV risk factor (HR = 3.5; 1 point), >1 CV risk factors (HR = 8.3; 2 points) and previous thrombosis (HR = 2.0; 1 point). A final three-tiered prognostic model for thrombosis prediction was developed as low (score 0), intermediate (score 1 or 2) and high risk (score 3) (p < 0.001). The hazard of thrombosis was 3.8 % in low-risk group, 16.7 % in the intermediate-risk group and 60 % in the high-risk group (p < 0.001). Patients with thrombotic complications during the follow-up had a significantly shorter survival (p = 0.018). The new score based on CV risk factors and previous thrombotic events allows a better patient selection within prognostic-risk groups and improved identification of the high-risk patients for thrombosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110(4):1092–7.

    Article  PubMed  CAS  Google Scholar 

  2. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 2006;32:171–3.

    Article  PubMed  Google Scholar 

  3. Passamonti F, Rumi E, Arcaini L, Boveri E, Elena C, Pietra D, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica. 2008;93(11):1645–51.

    Article  PubMed  Google Scholar 

  4. Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia. 2008;22(5):905–14.

    Article  PubMed  CAS  Google Scholar 

  5. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93.

    Article  PubMed  Google Scholar 

  6. Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.

    Article  PubMed  Google Scholar 

  7. Vannucchi AM, Guglielmelli P, Pieri L, Antonioli E, Bosi A. Treatment options for essential thrombocythemia and polycythemia vera. Expert Rev Hematol. 2009;2(1):41–55.

    Article  PubMed  Google Scholar 

  8. Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N. Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol. 2011;90(6):933–8.

    Article  PubMed  Google Scholar 

  9. Girodon F, Dutrillaux F, Broseus J, Mounier M, Goussot V, Bardonnaud P, et al. Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients. Leukemia. 2010;24(4):900–3.

    Article  PubMed  CAS  Google Scholar 

  10. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization- essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33.

    Article  PubMed  CAS  Google Scholar 

  11. Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117(22):5857–9.

    Article  PubMed  CAS  Google Scholar 

  12. Montanaro M, Latagliata R, Cedrone M, Spadea A, Rago A, Di Giandomenico J, et al. Thrombosis and survival in essential thrombocythemia: a regional study of 1,144 patients. Am J Hematol. 2014;89(5):542–6.

    Article  PubMed  Google Scholar 

  13. Alvarez-Larran A, Cervantes F, Bellosillo B, Giralt M, Julia A, Hernandez-Boluda JC, et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia. 2007;21:1218–23.

    Article  PubMed  CAS  Google Scholar 

  14. Wolansky AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81:159–66.

    Article  Google Scholar 

  15. Ruggeri M, Finazzi G, Tosetto A, Riva S, Rodeghiero F, Barbui T. No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol. 1998;103:772–7.

    Article  PubMed  CAS  Google Scholar 

  16. Besses C, Cervantes F, Pereira A, Florensa L, Sole F, Hernandez-Boluda JC, et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia. 1999;13:150–4.

    Article  PubMed  CAS  Google Scholar 

  17. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110:840–6.

    Article  PubMed  CAS  Google Scholar 

  18. Palandri F, Catani L, Testoni N, Ottaviani E, Polverelli N, Fiacchini M, et al. Long-term follow-up of 386 consecutive patients with essential thrombocythemia: safety of cytoreductive therapy. Am J Hematol. 2009;84:215–20.

    Article  PubMed  Google Scholar 

  19. Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia. 2008;22:1494–502.

    Article  PubMed  CAS  Google Scholar 

  20. Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88(6):507–16.

    Article  PubMed  CAS  Google Scholar 

  21. Lowe GDO. Common risk factors for both arterial and venous thrombosis. Br J Haematol. 2008;140:488–95.

    Article  PubMed  Google Scholar 

  22. Prandoni P. Venous thromboembolism and atherosclerosis: is there a link? J Thromb Haemost. 2007;5(Suppl 1):270–5.

    Article  PubMed  CAS  Google Scholar 

  23. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9–16.

    PubMed  Google Scholar 

  24. Jerjes-Sanchez C. Venous and arterial thrombosis: a continous spectrum of the same disease? Eur Heart J. 2005;26:3–4.

    Article  PubMed  Google Scholar 

  25. Prandoni P, Bilora F, Marchioli A, Bernardi E, Petrobelli F, Lensing AWA, et al. An association between atherosclerosis and venous thromboembolism. N Engl J Med. 2003;348:1435–41.

    Article  PubMed  Google Scholar 

  26. Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation. 2008;117(1):93–102.

    Article  PubMed  Google Scholar 

  27. Prandoni P. Links between arterial and venous disease. J Intern Med. 2007;262:341–50.

    Article  PubMed  CAS  Google Scholar 

  28. Bova C, Marchiori A, Noto A, Rossi V, Daniele F, Santoro C, et al. Incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism. A retrospective cohort study. Thromb Haemost. 2006;96:132–6.

    PubMed  CAS  Google Scholar 

  29. Di Minno MN, Tufano A, Ageno W, Prandoni P, Di Minno G. Identifying high-risk individuals for cardiovascular disease: similarities between venous and arterial thrombosis in perspective. A 2011 update. Intern Emerg Med. 2012;7(1):9–13.

    Article  PubMed  Google Scholar 

  30. Landolfi R, Di Gennaro L. Prevention of thrombosis in polycythemia vera and essential thrombocythemia. Haematologica. 2008;93:331–5.

    Article  PubMed  CAS  Google Scholar 

  31. Masciulli A, Barbui T, Marfisi RM, Cavazzina R, Finazzi G, Lunghi M, et al. How epidemiology of polycythemia vera has changed in the last 10 years: results from the whole prospective cohort of patients in CYTO-PV trial as compared with ECLAP prospective cohort. ASH Annual Meeting Abstracts. 2012;120:1748.

    Google Scholar 

  32. Delluc A, Malécot JM, Kerspern H, Nowak E, Carre JL, Mottier D, Le Gal G, et al. Lipid parameters, lipid lowering drugs and the risk of venous thromboembolism. Atherosclerosis. 2012;220(1):184–8.

    Article  PubMed  CAS  Google Scholar 

  33. Doggen CJ, Smith NL, Lemaitre RN, Heckbert SR, Roosendaal FR, Psaty BM. Serum lipid levels and the risk of venous thrombosis. Arterioscler Thromb Vasc Biol. 2004;24:1970–5.

    Article  PubMed  CAS  Google Scholar 

  34. Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851–61.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Ramcharan AS, Van Stralen KJ, Snoep JD, Mantel-Teeuwisse AK, Rosendaal FR, Doggen CJ. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis. J Thromb Haemost. 2009;7:514–20.

    Article  PubMed  CAS  Google Scholar 

  36. Poredos P, Jezovnik MK. Dyslipidemia, statins, and venous thromboembolisam. Semin Thromb Hemost. 2011;37(8):897–902.

    Article  PubMed  CAS  Google Scholar 

  37. Squizzato A, Romualdi E, Middeldorp S. Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. Cochrane Database Syst Rev. 2008;4:CD006503.

    Google Scholar 

  38. Tefferi A, Barbui T. Personalized management of essential thrombocythemia—application of recent evidence to clinical practice. Leukemia. 2013;27:1617–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by Ministry of education, science and technological development of the Republic of Serbia (175053).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Clinic for Hematology, Clinical Center of Serbia, Koste Todorovica 2, 11 000, Belgrade, Serbia

    Danijela Lekovic, Mirjana Gotic, Predrag Miljic, Mirjana Mitrovic & Ivo Elezovic

  2. Medical Faculty, University of Belgrade, Belgrade, Serbia

    Mirjana Gotic, Natasa Milic, Predrag Miljic & Ivo Elezovic

  3. Institute for Medical Statistics, University of Belgrade, Belgrade, Serbia

    Natasa Milic

  4. Institute for Medical Research, University of Belgrade, Belgrade, Serbia

    Vladan Cokic

Authors
  1. Danijela Lekovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mirjana Gotic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Natasa Milic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Predrag Miljic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mirjana Mitrovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vladan Cokic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ivo Elezovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Danijela Lekovic.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lekovic, D., Gotic, M., Milic, N. et al. The importance of cardiovascular risk factors for thrombosis prediction in patients with essential thrombocythemia. Med Oncol 31, 231 (2014). https://doi.org/10.1007/s12032-014-0231-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0231-1

Keywords

Search

Navigation