Internal and Emergency Medicine

, Volume 7, Issue 6, pp 509–515 | Cite as

Polycythemia vera: gender-related phenotypic differences

  • Raffaele Landolfi
  • Leonardo Di Gennaro
  • Maria Anna Nicolazzi
  • Igor Giarretta
  • RosaMaria Marfisi
  • Roberto Marchioli


In polycythemia vera, gender has recently been shown to influence the JAK2V617F allele burden, but its effect on the disease phenotype is unknown. This issue was investigated using the database of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study. The ECLAP Study recruited 1,638 polycythemic subjects and followed for 2.7 ± 1.3 years. At study entry, men, compared to women, had a higher prevalence of myocardial infarction (11.3 vs. 5.8%; P < 0.0001) and peripheral arterial disease (6.1 vs. 2.9%; P < 0.05) while a history of venous thrombosis was more common in women (11.4 vs. 7.9%, P = 0.016). Among 234 venous thrombosis, there were 39 splanchnic vein thromboses (33 extra-hepatic portal vein thromboses and 6 Budd-Chiari syndromes). Most of these events occurred as an early disease presentation in young female subjects. Women, compared to men, had higher platelet counts (average value 430 ± 213 vs. 375 ± 201 × 109/L; P < 0.0001) and lower hematocrits (0.46 ± 0.06 vs. 0.48 ± 0.06 l/l; P < 0.0001). Cholesterol plasma level, available in 995 subjects (61%), was lower in male patients (180.8 ± 43.1vs. 196 ± 46.6 mg/dl; P < 0.0001). During follow-up there were 205 major thromboses confirming an high incidence of myocardial infarction in men although not statistically significant (1.2 vs. 0.6 cases per 100 person-years; P > 0.05). These data show several gender-related differences both in the thrombotic diathesis and in the prevalence of vascular risk factors of PV patients.


Myeloproliferative neoplasms Polycythemia vera Thrombosis Gender 



The contribution of TizianoBarbui, Raimondo De Cristofaro and Luca Miele to data interpretation and discussion is gratefully acknowledged.

Conflict of interest



  1. 1.
    Landolfi R, Nicolazzi MA, Porfidia A, Di Gennaro L (2010) Polycythemia vera. Intern Emerg Med 5:375–384PubMedCrossRefGoogle Scholar
  2. 2.
    Vannucchi AM (2010) Insights into the pathogenesis and management of thrombosis in polycythemiavera and essential thrombocythemia. Intern Emerg Med 5:177–184PubMedCrossRefGoogle Scholar
  3. 3.
    Landolfi R, Di Gennaro L, Falanga A (2008) Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia 22:2020–2028PubMedCrossRefGoogle Scholar
  4. 4.
    Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T, European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators (2004) Efficacy and safety of low dose aspirin in polycythemiavera. N Engl J Med 350:114–124PubMedCrossRefGoogle Scholar
  5. 5.
    Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi RM, Tognoni G, Marchioli R, European Collaboration on Low-Dose Aspirin in Polycythemia Vera (2007) Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 109:2446–2452PubMedCrossRefGoogle Scholar
  6. 6.
    Akhter N, Milford-Beland S, Roe MT, Piana RN, Kao J, Shroff A (2009) Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR). Am Heart J 157:141–148PubMedCrossRefGoogle Scholar
  7. 7.
    Adams KF Jr, Sueta CA, Gheorghiade M, O’Connor CM, Schwartz TA, Koch GG, Uretsky B, Swedberg K, McKenna W, Soler-Soler J, Califf RM (1999) Gender differences in survival in advanced heart failure Insights from the FIRST study. Circulation 99:1816–1821PubMedCrossRefGoogle Scholar
  8. 8.
    Capodanno D, Angiolillo DJ (2010) Impact of race and gender on antithrombotic therapy. Thromb Haemost 104:471–484PubMedCrossRefGoogle Scholar
  9. 9.
    Berger U, Maywald O, Pfirrmann M, Lahaye T, Hochhaus A, Reiter A, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Queisser W, Hehlmann R, German CML-Study Group (2005) Genderaspects in chronic myeloid leukemia: long-term results from randomized studies. Leukemia 19:984–989PubMedCrossRefGoogle Scholar
  10. 10.
    Bauersachs RM, Riess H, Hach-Wunderle V, Gerlach H, Carnarius H, Eberle S, Rabe E, Schellong SM (2010) Impact of gender on the clinical presentation and diagnosis of deep-vein thrombosis. Thromb Haemost 103:710–717PubMedCrossRefGoogle Scholar
  11. 11.
    Davis MD, O’Fallon WM, Rogers RS, Rooke TW (2000) Natural history of erythromelalgia: presentation and outcome in 168 patients. Arch Dermatol 136:330–336PubMedCrossRefGoogle Scholar
  12. 12.
    Brière JB (2006) Budd-Chiari syndrome and portal vein thrombosis associated with myeloproliferative disorders: diagnosis and management. Semin Thromb Hemost 32:208–218PubMedCrossRefGoogle Scholar
  13. 13.
    Stein B, Williams D, Wang NY, Rogers O, Isaacs MA, Pemmaraju N, Spivak J, Moliterno A (2010) Sex differences in the JAK2V617F allele burden in the chronic myeloproliferative disorders. Haematologica 95:1090–1097PubMedCrossRefGoogle Scholar
  14. 14.
    Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, Marilus R, Tognoni G, Barbui T (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23:2224–2232PubMedCrossRefGoogle Scholar
  15. 15.
    National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 106:3143–3421Google Scholar
  16. 16.
    Lichtman MA, Rowe JM (2004) The relationship of patient age to the pathobiology of the clonal myeloid diseases. Semin Oncol 31:185–197PubMedCrossRefGoogle Scholar
  17. 17.
    Chait Y, Condat B, Casalz-Hatem D, Rufat P, Atmani S, Chaoui D, Guilmin F, Kiladjian JJ, Plessier A, Denninger MH, Casadevall N, Valla D, Brière JB (2005) Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic thrombosis. Br J Hematol 129:553–560CrossRefGoogle Scholar
  18. 18.
    Tondeur S, Boutruche S, Biron-Andréani C, Schved JF (2009) Prevalence of the JAK2 V617F mutation associated with splanchnic vein thrombosis. A 10-year retrospective study. Thromb Haemost 101:787–789PubMedGoogle Scholar
  19. 19.
    Bittencourt PL, Couto CA, Ribeiro DD (2009) Portal vein thrombosis and Budd-Chiari syndrome. Clin Liver Dis 13:127–144PubMedCrossRefGoogle Scholar
  20. 20.
    Gangat N, Wolanskhyj AP, Tefferi A (2006) Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates and prognostic implications. Eur J Hematol 77:327–333CrossRefGoogle Scholar
  21. 21.
    De Stefano V, Martinelli I (2010) Splanchnic vein thrombosis: clinical presentation, risk factors and treatment. Intern Emerg Med 5:487–494PubMedCrossRefGoogle Scholar
  22. 22.
    Spanoudakis E, Bazdiara I, Kotsianidis I, Margaritis D, Goutzouvelidis A, Christoforidou A, Tsatalas C, Bourikas G (2009) Hydroxyurea is effective in reducing JAK2V617F mutated clone size in the peripheral blood of essential thrombocythemia and polycythemiavera patients. Ann Hematol 88:629–632PubMedCrossRefGoogle Scholar
  23. 23.
    Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R et al (2007) Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 110:840–846PubMedCrossRefGoogle Scholar
  24. 24.
    Tefferi A, Strand JJ, Lasho TL, Knudson RA, Finke CM, Gangat N, Pardanani A, Hanson CA, Ketterling RP (2007) Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia 21:2074–2075PubMedCrossRefGoogle Scholar
  25. 25.
    Finazzi G, Rambaldi A, Guerini V, Carobbio A, Barbui T (2007) Risk of thrombosis in patients with essential thrombocythemia and polycythemiavera according to JAK2 V617F mutation status. Haematologica 92:135–136PubMedCrossRefGoogle Scholar
  26. 26.
    Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Dellacasa CM, Salmoiraghi S, Delaini F, Rambaldi A, Barbui T (2009) JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemiavera. Exp Hematol 37:1016–1021PubMedCrossRefGoogle Scholar
  27. 27.
    Boissinot M, Lippert E, Girodon F, Dobo I, Fouassier M, Masliah C, Praloran V, Hermouet S (2006) Latent myeloproliferative disorder revealed by the JAK2-V617F mutation and endogenous megakaryocytic colonies in patients with splanchnic vein thrombosis. Blood 108:3223–3224PubMedCrossRefGoogle Scholar
  28. 28.
    Martinelli I, De Stefano V (2010) Rare thromboses of cerebral, splanchnic and upper-extremity veins. A narrative review. Thromb Haemost 103:1136–1144PubMedCrossRefGoogle Scholar
  29. 29.
    Gilbert HS, Ginsberg H, Fagerstrom R, Brown WV (1981) Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity. Am J Med 71:595–602PubMedCrossRefGoogle Scholar
  30. 30.
    Spanos GA, Bajaj K, Rosner F (1981) Hypocholesterolemia in myeloproliferative disorders. Arch Intern Med 141:137–138PubMedCrossRefGoogle Scholar

Copyright information

© SIMI 2011

Authors and Affiliations

  • Raffaele Landolfi
    • 1
  • Leonardo Di Gennaro
    • 1
  • Maria Anna Nicolazzi
    • 1
  • Igor Giarretta
    • 1
  • RosaMaria Marfisi
    • 2
  • Roberto Marchioli
    • 2
  1. 1.Institute of Internal Medicine and Geriatrics, Haemostasis Research CenterCatholic University School of MedicineRomeItaly
  2. 2.Laboratory of Clinical Epidemiology of Cardiovascular DiseaseSanta Maria ImbaroItaly

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