Other presentations
While generally a disease of middle-aged and older people, polycythemia vera (PV) can occur in all age groups, including children (although extremely rare).[9]Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 2006 Apr;32(3):171-3.
http://www.ncbi.nlm.nih.gov/pubmed/16673273?tool=bestpractice.com
[10]Cario H, McMullin MF, Pahl HL. Clinical and hematological presentation of children and adolescents with polycythemia vera. Ann Hematol. 2009 Aug;88(8):713-9.
http://www.ncbi.nlm.nih.gov/pubmed/19468728?tool=bestpractice.com
[11]Verstovsek S, Yu J, Scherber RM, et al. Changes in the incidence and overall survival of patients with myeloproliferative neoplasms between 2002 and 2016 in the United States. Leuk Lymphoma. 2022 Mar;63(3):694-702.
https://www.tandfonline.com/doi/full/10.1080/10428194.2021.1992756
http://www.ncbi.nlm.nih.gov/pubmed/34689695?tool=bestpractice.com
PV is slightly more common in men.[11]Verstovsek S, Yu J, Scherber RM, et al. Changes in the incidence and overall survival of patients with myeloproliferative neoplasms between 2002 and 2016 in the United States. Leuk Lymphoma. 2022 Mar;63(3):694-702.
https://www.tandfonline.com/doi/full/10.1080/10428194.2021.1992756
http://www.ncbi.nlm.nih.gov/pubmed/34689695?tool=bestpractice.com
At initial presentation, it is reported that 12% to 39% of patients have major thrombosis, and 1.7% to 20% have major bleeding.[2]Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005 Feb;128(3):275-90.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2004.05277.x
http://www.ncbi.nlm.nih.gov/pubmed/15667529?tool=bestpractice.com
[12]Grunwald MR, Stein BL, Boccia RV, et al. Clinical and disease characteristics from REVEAL at time of enrollment (baseline): prospective observational study of patients with polycythemia vera in the United States. Clin Lymphoma Myeloma Leuk. 2018 Dec;18(12):788-95.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148982
http://www.ncbi.nlm.nih.gov/pubmed/30245100?tool=bestpractice.com
The skin and mucous membranes are common sites of bleeding; gastrointestinal bleeding is less frequent, but can be severe.[2]Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005 Feb;128(3):275-90.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2004.05277.x
http://www.ncbi.nlm.nih.gov/pubmed/15667529?tool=bestpractice.com
Classic symptoms of PV include headache, generalized weakness/fatigue, pruritus, paresthesias, tinnitus, blurry vision, arthralgia, abdominal discomfort, hyperhidrosis, plethora, and ruddy cyanosis; however, it is unusual for patients to present with all these symptoms.[13]Vannucchi AM. How I treat polycythemia vera. Blood. 2014 Nov 20;124(22):3212-20.
http://www.bloodjournal.org/content/124/22/3212.long
http://www.ncbi.nlm.nih.gov/pubmed/25278584?tool=bestpractice.com
A palpable spleen is reported in approximately one third of patients.[14]Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013 Sep;27(9):1874-81.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768558
http://www.ncbi.nlm.nih.gov/pubmed/23739289?tool=bestpractice.com
Additionally, a significant proportion of patients (predominantly young women) who present with idiopathic Budd-Chiari syndrome, whose blood counts may be normal, will eventually develop a PV phenotype.[15]Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari Syndrome. Gastroenterology. 2006 Jun;130(7):2031-8.
http://www.ncbi.nlm.nih.gov/pubmed/16762626?tool=bestpractice.com
Some patients may have pathologically and molecularly proven PV, without overt elevations in hemoglobin or hematocrit.[16]Barbui T, Thiele J, Carobbio A, et al. Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol. 2014;89:199-202.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23617/full
http://www.ncbi.nlm.nih.gov/pubmed/24166817?tool=bestpractice.com
This is known as “masked PV” as the diagnosis is not obvious from the patient’s hemoglobin/hematocrit. Masked PV patients are more frequently male, and tend to present with higher platelet counts and increased reticulin fibrosis in the bone marrow.[16]Barbui T, Thiele J, Carobbio A, et al. Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol. 2014;89:199-202.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23617/full
http://www.ncbi.nlm.nih.gov/pubmed/24166817?tool=bestpractice.com
Patients experience the same spectrum of complications as with overt PV. However, they have worse survival (particularly among those ages >65 years and those with leukocytosis) and higher rates of progression to myelofibrosis and acute leukemia.[16]Barbui T, Thiele J, Carobbio A, et al. Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol. 2014;89:199-202.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23617/full
http://www.ncbi.nlm.nih.gov/pubmed/24166817?tool=bestpractice.com
[17]Barbui T, Thiele J, Gisslinger H, et al. Masked polycythemia vera (mPV): results of an international study. Am J Hematol. 2014 Jan;89(1):52-4.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23585/abstract
http://www.ncbi.nlm.nih.gov/pubmed/23996471?tool=bestpractice.com
Masked PV requires careful pathologic distinction from essential thrombocythemia when accompanied by thrombocytosis.[18]Barbui T, Thiele J, Carobbio A, et al. Discriminating between essential thrombocythemia and masked polycythemia vera in JAK2 mutated patients. Am J Hematol. 2014 Jun;89(6):588-90.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23694/full
http://www.ncbi.nlm.nih.gov/pubmed/24535932?tool=bestpractice.com
Delayed/missed recognition and a lower intensity of treatment of masked PV may contribute to worse outcomes.[19]Lussana F, Carobbio A, Randi ML, et al. A lower intensity of treatment may underlie the increased risk of thrombosis in young patients with masked polycythaemia vera. Br J Haematol. 2014 Nov;167(4):541-6.
https://www.doi.org/10.1111/bjh.13080
http://www.ncbi.nlm.nih.gov/pubmed/25130523?tool=bestpractice.com
High clinical vigilance for a possible PV diagnosis is essential in the presence of suggestive symptoms or complications (e.g., otherwise unexplained thrombosis).[18]Barbui T, Thiele J, Carobbio A, et al. Discriminating between essential thrombocythemia and masked polycythemia vera in JAK2 mutated patients. Am J Hematol. 2014 Jun;89(6):588-90.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.23694/full
http://www.ncbi.nlm.nih.gov/pubmed/24535932?tool=bestpractice.com