Diagnostic Considerations

Polycythemia is characterized by increased cell counts in all cell lines in the myeloid series (ie, red blood cells, white blood cells [preferentially granulocytes], and platelets). Thus, conditions that involve individual cell lines, such as the following, must be excluded:

Erythrocytosis - Causes include secondary polycythemia (an increase in red blood cell [RBC] counts, typically due to chronic hypoxemia), familial erythrocythemia, and relative polycythemia (a benign condition in which RBC numbers are normal but plasma volume is contracted, due to dehydration or to reduced venous compliance).
Granulocytosis from infections or mobilization by secondary causes, as in leukemoid reactions
Thrombocytosis from bleeding and iron deficiency

Diagnostic laboratory tests have been developed to increase the ability to identify primary myeloproliferative diseases (MPDs) and to differentiate them from reactive conditions associated with increased blood cell levels, which can mimic MPDs. Once an MPD (Philadelphia chromosome negative [Ph–]) is documented, it must be differentiated from the following conditions, which have manifestations that overlap with polycythemia vera (PV):

Differential Diagnoses

Workup

National Cancer Institute. PDQ® Chronic Myeloproliferative Neoplasms Treatment. National Cancer Institute. Available at http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#link/_5. November 4, 2020; Accessed: September 16, 2021.
Tefferi A, Vannucchi AM, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia. 2021 Sep 3. 12(4):339-51. [QxMD MEDLINE Link].
Lu X, Chang R. Polycythemia Vera. 2021 Jan. 5(5):327-31. [QxMD MEDLINE Link]. [Full Text].
Streiff MB, Smith B, Spivak JL. The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood. 2002 Feb 15. 99(4):1144-9. [QxMD MEDLINE Link]. [Full Text].
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19. 127 (20):2391-405. [QxMD MEDLINE Link]. [Full Text].
James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28. 434(7037):1144-8. [QxMD MEDLINE Link].
Kralovics R, Teo SS, Buser AS, et al. Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. Blood. 2005 Nov 15. 106(10):3374-6. [QxMD MEDLINE Link]. [Full Text].
Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005 Apr. 7(4):387-97. [QxMD MEDLINE Link]. [Full Text].
Guglielmelli P, Barosi G, Pieri L, et al. JAK2V617F mutational status and allele burden have little influence on clinical phenotype and prognosis in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis. Haematologica. 2009 Jan. 94(1):144-6. [QxMD MEDLINE Link]. [Full Text].
Mustjoki S, Borze I, Lasho TL, et al. JAK2V617F mutation and spontaneous megakaryocytic or erythroid colony formation in patients with essential thrombocythaemia (ET) or polycythaemia vera (PV). Leuk Res. 2009 Jan. 33(1):54-9. [QxMD MEDLINE Link].
Vannucchi AM. From leeches to personalized medicine: evolving concepts in the management of polycythemia vera. Haematologica. 2017 Jan. 102 (1):18-29. [QxMD MEDLINE Link]. [Full Text].
Palandri F, Mora B, Gangat N, Catani L. Is there a gender effect in polycythemia vera?. Ann Hematol. 2021 Jan. 100 (1):11-25. [QxMD MEDLINE Link]. [Full Text].
Rusak T, Ciborowski M, Uchimiak-Owieczko A, Piszcz J, Radziwon P, Tomasiak M. Evaluation of hemostatic balance in blood from patients with polycythemia vera by means of thromboelastography: The effect of isovolemic erythrocytapheresis. Platelets. 2011 Nov 18. [QxMD MEDLINE Link].
Spivak JL, Considine M, Williams DM, Talbot CC Jr, Rogers O, Moliterno AR, et al. Two clinical phenotypes in polycythemia vera. N Engl J Med. 2014 Aug 28. 371(9):808-17. [QxMD MEDLINE Link].
Cabagnols X, Favale F, Pasquier F, Messaoudi K, Defour JP, Ianotto JC, et al. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients. Blood. 2016 Jan 21. 127 (3):333-42. [QxMD MEDLINE Link].
Tefferi A, Barbui T. Essential Thrombocythemia and Polycythemia Vera: Focus on Clinical Practice. Mayo Clin Proc. 2015 Sep. 90 (9):1283-93. [QxMD MEDLINE Link].
Barbui T, Thiele J, Gisslinger H, Finazzi G, Carobbio A, Rumi E, et al. Masked polycythemia vera (mPV): results of an international study. Am J Hematol. 2014 Jan. 89 (1):52-4. [QxMD MEDLINE Link]. [Full Text].
Wang JC, Shi G, Baptiste S, Yarotska M, Sindhu H, Wong C, et al. Quantification of IGF-1 Receptor May Be Useful in Diagnosing Polycythemia Vera-Suggestion to Be Added to Be One of the Minor Criterion. PLoS One. 2016 Nov 3. 11 (11):e0165299. [QxMD MEDLINE Link]. [Full Text].
Bose P, Verstovsek S. JAK2 inhibitors for myeloproliferative neoplasms: what is next?. Blood. 2017 Jul 13. 130 (2):115-125. [QxMD MEDLINE Link].
McMullin MF, Wilkins BS, Harrison CN. Management of polycythaemia vera: a critical review of current data. Br J Haematol. 2015 Oct 22. [QxMD MEDLINE Link].
FDA Approves Treatment for Rare Blood Disease. U.S. Food & Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-blood-disease. November 12, 2021; Accessed: November 20, 2021.
Squizzato A, Romualdi E, Passamonti F, Middeldorp S. Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. Cochrane Database Syst Rev. 2013 Apr 30. 4:CD006503. [QxMD MEDLINE Link].
Alvarez-Larrán A, Martínez-Avilés L, Hernández-Boluda JC, Ferrer-Marín F, Antelo ML, Burgaleta C, et al. Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea. Ann Hematol. 2014 Jul 2. [QxMD MEDLINE Link].
Alvarez-Larrán A, Kerguelen A, Hernández-Boluda JC, et al. Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br J Haematol. 2016 Mar. 172 (5):786-93. [QxMD MEDLINE Link].
Barbui T, Masciulli A, Marfisi MR, Tognoni G, Finazzi G, Rambaldi A, et al. White blood cell counts and thrombosis in polycythemia vera: a subanalysis of the CYTO-PV study. Blood. 2015 Jul 23. 126 (4):560-1. [QxMD MEDLINE Link]. [Full Text].
Bewersdorf JP, Giri S, Wang R, Podoltsev N, Williams RT, Tallman MS, et al. Interferon alpha therapy in essential thrombocythemia and polycythemia vera-a systematic review and meta-analysis. Leukemia. 2021 Jun. 35 (6):1643-1660. [QxMD MEDLINE Link]. [Full Text].
Abu-Zeinah G, Krichevsky S, Cruz T, Hoberman G, Jaber D, Savage N, et al. Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival. Leukemia. 2021 Sep. 35 (9):2592-2601. [QxMD MEDLINE Link].
Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar. 7 (3):e196-e208. [QxMD MEDLINE Link].
Besremi. European Medicines Agency. Available at https://www.ema.europa.eu/en/medicines/human/EPAR/besremi. February 22, 2021; Accessed: September 20, 2021.
Marchioli R, et al; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3. 368 (1):22-33. [QxMD MEDLINE Link].
Berk PD, Goldberg JD, Donovan PB, et al. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol. 1986 Apr. 23(2):132-43. [QxMD MEDLINE Link].
Weinfeld A, Swolin B, Westin J. Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications. Eur J Haematol. 1994 Mar. 52(3):134-9. [QxMD MEDLINE Link].
Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety: a Polycythemia Vera Study Group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997 Jan. 34(1):17-23. [QxMD MEDLINE Link].
Huang BT, Zeng QC, Zhao WH, Li BS, Chen RL. Interferon a-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation. Leuk Res. 2014 Jul 15. [QxMD MEDLINE Link].
Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8. 350(2):114-24. [QxMD MEDLINE Link]. [Full Text].
Vannucchi AM. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Apr 23. 372 (17):1670-1. [QxMD MEDLINE Link]. [Full Text].
Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, et al. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2015 Aug. 1 (5):643-51. [QxMD MEDLINE Link].
Slakey DP, Klein AS, Venbrux AC, Cameron JL. Budd-Chiari syndrome: current management options. Ann Surg. 2001 Apr. 233(4):522-7. [QxMD MEDLINE Link]. [Full Text].
Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2017 Jan. 92 (1):94-108. [QxMD MEDLINE Link].
Khanal N, Giri S, Upadhyay S, Shostrom VK, Pathak R, Bhatt VR. Risk of second primary malignancies and survival of adult patients with polycythemia vera: A United States population-based retrospective study. Leuk Lymphoma. 2016. 57 (1):129-33. [QxMD MEDLINE Link].
Nelson R. FDA Approves Fedratinib for the Treatment of Myelofibrosis. Medscape Medical News. Available at https://www.medscape.com/viewarticle/916928. August 16, 2019; Accessed: August 16, 2019.
Abdulkarim K, Girodon F, Johansson P, et al. AML transformation in 56 patients with Ph- MPD in two well defined populations. Eur J Haematol. 2009 Feb. 82(2):106-11. [QxMD MEDLINE Link].
Siebolts U, Breuhahn K, Hennecke A, Schultze JL, Wickenhauser C. Imbalance of DNA-dependent protein kinase subunits in polycythemia vera peripheral blood stem cells. Int J Cancer. 2009 Feb 1. 124(3):600-7. [QxMD MEDLINE Link].
Gotlib J, Kiladjian JJ, Vannucchi A, Rambaldi A, Reiter A, Shomali W, et al. A Phase 2 Study of Pemigatinib (FIGHT-203; INCB054828) in Patients with Myeloid/Lymphoid Neoplasms (MLNs) with Fibroblast Growth Factor Receptor 1 (FGFR1) Rearrangement (MLN FGFR1). Blood. 2021 Nov 23(138(suppl 1): 385. Presented at the 64th American Society of Hematology Virtual Meeting 2021. [Full Text].

Media Gallery

Bone marrow film at 100X magnification demonstrating hypercellularity and increased number of megakaryocytes. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Blood film at 400X magnification demonstrating polyglobulia and thrombocytosis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Bone marrow film at 400X magnification demonstrating dominance of erythropoiesis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
This blood film at 10,000X magnification shows a giant platelet and an eosinophil. Erythrocytes show signs of hypochromia as a result of repeated phlebotomies. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

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Author

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Coauthor(s)

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Sara J Grethlein, MD, MBA, FACP Executive Medical Director and Medical Oncologist, Swedish Cancer Institute

Sara J Grethlein, MD, MBA, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Women's Association, American Society of Clinical Oncology, American Society of Hematology, Gold Humanism Honor Society, Leukemia and Lymphoma Society

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Sections Polycythemia Vera
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Polycythemia Vera Differential Diagnoses

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Differential Diagnoses

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