Polycythemia vera

Last updated: June 29, 2022

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Polycythemia vera is a chronic myeloproliferative neoplasm most commonly caused by a gain of function mutation in the JAK2 gene, leading to erythrocytosis with or without increases in granulocytes and platelets. The elevated blood cell mass results in hyperviscosity, which may manifest with fatigue, facial flushing, pruritus, erythromelalgia, headaches, dizziness, and, in severe cases, thromboembolic events (e.g., stroke, Budd-Chiari syndrome). Diagnosis is confirmed if other causes of polycythemia are ruled out (e.g., relative polycythemia, hypoxia-induced polycythemia, autonomous EPO production) and diagnostic criteria for polycythemia vera are met. Management of polycythemia vera focuses on preventing thrombotic and bleeding events and treating associated symptoms (e.g., pruritus, gout). Therapeutic phlebotomy and aspirin are indicated in all patients. Additionally, patients with high-risk polycythemia vera require cytoreductive therapies and, possibly, anticoagulation. Patients should be monitored carefully for the development of complications and transformation of polycythemia vera to another hematologic malignancy, e.g., post-PV myelofibrosis, myelodysplasia, or acute myelogenous leukemia (AML).

Epidemiological data refers to the US, unless otherwise specified.


Patients with polycythemia vera are at increased risk of thrombosis and bleeding.

Approach [3][9][10][11]

Erythrocytosis associated with normal oxygen saturation and decreased serum EPO levels is strongly suggestive of polycythemia vera. Erythrocytosis associated with elevated serum EPO or decreased oxygen saturation suggests secondary polycythemia caused by chronic hypoxia.

The first presentation in patients with polycythemia vera may be a thrombotic event, in particular, hepatic vein thrombosis. Maintain a low threshold for working up older patients with new thrombosis. [13]

Diagnostic criteria

Diagnostic criteria for polycythemia vera [9][10]

Findings
Major criteria
Minor criterion

Diagnostic confirmation

  • All three major criteria are present

  • OR JAK2 mutation is not detected but two major criteria PLUS minor criterion are met

Hemoglobin levels may be normal in the prepolycythemic (masked) phase of polycythemia vera, elevated during the overt polycythemic phase, and then decreased in post-PV myelofibrosis (the spent phase). [13][14]

Bone marrow biopsy may not be routinely required in patients with extremely elevated Hgb and Hct (i.e., : Hgb > 18.5 g/dL, Hct 55.5%; : Hgb > 16.5 g/dL, Hct 49.5%). [3][9][10]

Findings on routine laboratory studies [3]

Confirmatory laboratory studies are detailed in “Diagnostic criteria for polycythemia vera.” Additional findings on routine laboratory studies for polycythemia include: [10][15]

Polycythemia vera may manifest with erythrocytosis alone or, in > 50% of patients, erythrocytosis in combination with leukocytosis and/or thrombocytosis. [9]

In patients with polycythemia vera and iron deficiency, microscopic findings of iron deficiency anemia (i.e., microcytic hypochromic anemia) are seen on peripheral blood smear, but with elevated rather than decreased hemoglobin levels. [13][17]

Microcytic erythrocytosis is only associated with polycythemia vera, beta-thalassemia trait, and hypoxic erythrocytosis. [13][17]

Causes of polycythemia [17]
Definition Characteristic features Underlying conditions

Primary polycythemia

Secondary polycythemia Physiologically appropriate secondary polycythemia
  • RBC mass: ↑
  • EPO:
  • SaO2: ↓ or normal
  • Expected plasma volume: normal
Physiologically inappropriate secondary polycythemia
Medication-induced polycythemia
Relative polycythemia
  • An increase in RBCs in a set blood volume caused by a decreased plasma volume
  • RBC mass: normal or minimally ↑
  • EPO: normal
  • SaO2: normal
  • Expected plasma volume: ↓

An elevated EPO suggests secondary polycythemia. [17]

The differential diagnoses listed here are not exhaustive.

Approach [3][11][15][24]

The management of polycythemia vera focuses on decreasing the risk of thromboembolic events, which are the most common cause of mortality in patients with polycythemia vera. [3]

Hemopoietic stem cell transplant is not used in the management of polycythemia vera but may be considered in post-PV myelofibrosis. [13][24]

Reduction of blood cell counts [9][11][15][28]

Regular therapeutic phlebotomy

  • Indications: all patients [3][9][11]
  • Procedure: removal of blood (e.g., 250–500 mL) via venipuncture at scheduled intervals
  • Frequency: based on the patient's response to treatment . [3]

Cytoreductive therapy [3][11][24][26]

JAK2 inhibitors are highly effective at treating symptomatic splenomegaly; splenectomy is now rarely required in patients with polycythemia vera. [17]
Do not treat iron deficiency in patients with polycythemia vera; maintaining iron deficiency prevents rapid reexpansion of RBC mass after phlebotomy. [17]

Further prevention of thromboembolic events [11][15][24]

Smoking cessation is associated with a decreased risk of thrombosis. [3]

Patients with extreme thrombocytosis may develop acquired von Willebrand disease. If platelet count is > 1 million/μL, perform a ristocetin cofactor assay and consider stopping aspirin if ristocetin cofactor activity is < 20%. [15]

Symptomatic management [11][17]

Polycythemia vera is a potentially life-threatening disease because of the numerous complications associated with it.

Thrombotic complications [5][30]

Hemorrhagic complications [5]

Gout [5]

Late stages [5]

We list the most important complications. The selection is not exhaustive.

  • Without treatment: mortality within 2 years of diagnosis (typically due to thrombotic complications)
  • With treatment: median survival of 13.5 years; 24 years in those diagnosed before 60 years of age
  • Progression to post-PV myelofibrosis: 6–15% of patients over 15 years
  • Progression to AML or myelodysplastic syndrome: 5–18% of patients over 15 years
  1. Khattak SA, Ahmed S, Anwar J, Bozdar M. Frequency of Janus associated kinase 2 (V617F) mutation in patients of polycythemia vera.. J Coll Physicians Surg Pak. 2012; 22 (2): p.80-3.
  2. Raedler LA. Diagnosis and Management of Polycythemia Vera: Proceedings from a Multidisciplinary Roundtable. Am Health Drug Benefits. 2014; 7 (7 Suppl 3): p.S36-47.
  3. Jackson N, Burt D, Crocker J, Boughton B. Skin mast cells in polycythaemia vera relationship to the pathogenesis and treatment of pruritus. Br J Dermatol. 1987; 116 (1): p.21–29. doi: 10.1111/j.1365-2133.1987.tb05787.x . | Open in Read by QxMD
  4. Saini KS, Patnaik MM, Tefferi A. Polycythemia vera-associated pruritus and its management. Eur J Clin Invest. 2010; 40 (9): p.828-834. doi: 10.1111/j.1365-2362.2010.02334.x . | Open in Read by QxMD
  5. Wollina U. Burning feet in polycythemia vera – peripheral sensorimotor axonal neuropathy with erythromelalgia. International Journal of General Medicine. 2015 : p.69. doi: 10.2147/ijgm.s78848 . | Open in Read by QxMD
  6. Vannucchi AM, Guglielmelli P. What are the current treatment approaches for patients with polycythemia vera and essential thrombocythemia?. Hematology Am Soc Hematol Educ Program. 2017; 2017 (1): p.480-488. doi: 10.1182/asheducation-2017.1.480 . | Open in Read by QxMD
  7. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127 (20): p.2391-2405. doi: 10.1182/blood-2016-03-643544 . | Open in Read by QxMD
  8. Fox S, Griffin L, Robinson Harris D. Polycythemia Vera: Rapid Evidence Review. Am Fam Physician. 2021; 103 (11): p.680-687.
  9. Tefferi A, Vannucchi AM, Barbui T. Polycythemia vera treatment algorithm 2018. Blood Cancer J. 2018; 8 (1). doi: 10.1038/s41408-017-0042-7 . | Open in Read by QxMD
  10. Szybinski J, Meyer SC. Genetics of Myeloproliferative Neoplasms. Hematol Oncol Clin North Am. 2021; 35 (2): p.217-236. doi: 10.1016/j.hoc.2020.12.002 . | Open in Read by QxMD
  11. Caligiuri M, Levi MM, Kaushansky K, et al. Williams Hematology, 9E. McGraw-Hill Education / Medical ; 2015
  12. Maslah N, Soret J, Dosquet C, et al. Masked polycythemia vera: analysis of a single center cohort of 2480 red cell masses. Haematologica. 2019; 105 (3): p.e95-e97. doi: 10.3324/haematol.2018.215582 . | Open in Read by QxMD
  13. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management. Am J Hematol. 2020; 95 (12): p.1599-1613. doi: 10.1002/ajh.26008 . | Open in Read by QxMD
  14. Nersesjan V, Zervides KA, Sørensen AL, Kjær L, Skov V, Hasselbalch HC. The red blood cell count and the erythrocyte sedimentation rate in the diagnosis of polycythaemia vera. Eur J Haematol. 2019; 104 (1): p.46-54. doi: 10.1111/ejh.13334 . | Open in Read by QxMD
  15. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  16. Ginzburg YZ, Feola M, Zimran E, Varkonyi J, Ganz T, Hoffman R. Dysregulated iron metabolism in polycythemia vera: etiology and consequences. Leukemia. 2018; 32 (10): p.2105-2116. doi: 10.1038/s41375-018-0207-9 . | Open in Read by QxMD
  17. McMullin MF. Diagnosis and management of congenital and idiopathic erythrocytosis. Ther Adv Hematol. 2012; 3 (6): p.391-398. doi: 10.1177/2040620712458947 . | Open in Read by QxMD
  18. Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014; 69 (6): p.725-35. doi: 10.1093/gerona/glt154 . | Open in Read by QxMD
  19. Lundby C, Thomsen JJ, Boushel R, et al. Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J Physiol. 2006; 578 (1): p.309-314. doi: 10.1113/jphysiol.2006.122689 . | Open in Read by QxMD
  20. Al-Sharefi A, Mohammed A, Abdalaziz A, Jayasena CN. Androgens and Anemia: Current Trends and Future Prospects. Front Endocrinol (Lausanne). 2019; 10 . doi: 10.3389/fendo.2019.00754 . | Open in Read by QxMD
  21. J Kelly Smith. Gaisbock's Syndrome: A Case Study. Clin Med Rev Case Rep. 2017; 4 (7). doi: 10.23937/2378-3656/1410175 . | Open in Read by QxMD
  22. Spivak JL. Myeloproliferative Neoplasms. N Engl J Med. 2017; 376 (22): p.2168-2181. doi: 10.1056/nejmra1406186 . | Open in Read by QxMD
  23. Padmanabhan A, Connelly‐Smith L, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019; 34 (3): p.171-354. doi: 10.1002/jca.21705 . | Open in Read by QxMD
  24. Tefferi A, Vannucchi AM, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia. 2021; 35 (12): p.3339-3351. doi: 10.1038/s41375-021-01401-3 . | Open in Read by QxMD
  25. Iurlo A, Cattaneo D, Bucelli C, Baldini L. New Perspectives on Polycythemia Vera: From Diagnosis to Therapy. Int J Mol Sci. 2020; 21 (16): p.5805. doi: 10.3390/ijms21165805 . | Open in Read by QxMD
  26. Vannucchi AM, Harrison CN. Emerging treatments for classical myeloproliferative neoplasms. Blood. 2017; 129 (6): p.693-703. doi: 10.1182/blood-2016-10-695965 . | Open in Read by QxMD
  27. Tham SW, Giles M. Current pain management strategies for patients with erythromelalgia: a critical review. J Pain Res. 2018; Volume 11 : p.1689-1698. doi: 10.2147/jpr.s154462 . | Open in Read by QxMD
  28. Titmarsh GJ, Duncombe AS, McMullin MF, et al. How common are myeloproliferative neoplasms? A systematic review and meta-analysis. Am J Hematol. 2014; 89 (6): p.581-7. doi: 10.1002/ajh.23690 . | Open in Read by QxMD
  29. Polycythemia vera. https://rarediseases.org/rare-diseases/polycythemia-vera/. Updated: October 8, 2018. Accessed: June 24, 2022.
  30. Griesshammer M, Kiladjian JJ, Besses C. Thromboembolic events in polycythemia vera. Ann Hematol. 2019; 98 (5): p.1071-1082. doi: 10.1007/s00277-019-03625-x . | Open in Read by QxMD
  31. Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014; 124 (16): p.2507-13; quiz 2615. doi: 10.1182/blood-2014-05-579136 . | Open in Read by QxMD

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