Polycythemia vera

In oncology, polycythemia vera (PV) is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells.<ref name=britannica.com/> Approximately 98%<ref name="auto12">Template:Cite journal</ref><ref name="auto10">Template:Cite web</ref> of PV patients have a JAK2 gene mutation in their blood-forming cells<ref name="auto15">Template:Cite journal</ref><ref name="auto11">Most commonly resulting in a single amino acid change in its protein product from valine to phenylalanine at position 617.Template:Cite journal</ref> (compared with 0.1-0.2% of the general population).<ref name="auto9">Template:Cite journal</ref><ref name="auto14">Template:Cite journal</ref>

Most of the health concerns associated with PV, such as thrombosis, are caused by the blood being thicker as a result of the increased red blood cells.

PV may be asymptomatic. Possible symptoms, if any do occur, include fatigue, itching (pruritus), particularly after exposure to warm water, and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin.

Treatment consists primarily of blood withdrawals (phlebotomy) and oral meds.

PV is more common in the elderly.

Classification

PV is code 2A20.4 in the ICD-11.<ref>Template:Cite web</ref> It is a myeloproliferative neoplasm (MPN).<ref>Template:Cite web</ref> It is a primary form of polycythemia.

Pathophysiology

Approximately 98%<ref name="auto12"/><ref name="auto10"/> of PV patients have a mutation in a tyrosine kinase–encoding gene, JAK2, in their blood-forming cells<ref name="auto15"/><ref name="auto11"/> (compared with 0.1-0.2% of the general population).<ref name="auto9"/><ref name="auto14"/>

This acts in signaling pathways of the EPO receptor, making those cells proliferate independently from EPO. PV is associated with a low serum level of the hormone erythropoietin (EPO), in contrast to secondary polycythemias.<ref>Template:Cite book</ref>Template:Page number needed

While the mutation is a JAK2 V617F in 95% of patients, JAK2 exon 12 mutations have also been observed.<ref name="auto"/>

Signs and symptoms

Symptoms

People with PV can be asymptomatic.<ref>[Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York</ref>

Possible symptoms of PV<ref name="auto7">Template:Cite web</ref><ref name="auto6">Template:Cite web</ref> that may aid identification include;

• pruritus (itching), particularly after exposure to warm water (such as when taking a bath),<ref>Template:Cite journal</ref> which may be due to abnormal histamine release<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> or prostaglandin production.<ref>Template:Cite journal</ref> Such itching is present in 40%-55% of patients with PV.<ref name="pvsg"/><ref name="auto5">Template:Cite journal</ref>
• erythromelalgia,<ref>Template:Cite journal</ref> a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Other possible symptoms of PV include night sweats and fatigue.<ref name="auto7"/><ref name="auto6"/>

No symptoms are required for diagnosis.

Other diseases that may be present with PV

Other diseases that may be present with PV include;

• An enlarged spleen, a manageable condition, may occur<ref name="auto18">Template:Cite web</ref> and may cause the spleen to be palpable in some patients. This may be associated with both the V617F mutation and the development of myelofibrosis.<ref>Template:Cite journal</ref>
• Swollen joints (Gout)<ref name="auto18"/>
• Peptic ulcers.<ref name="auto18"/>

Diagnosis

Diagnostic criteria

WHO 2016

Diagnostic criteria for polycythemia vera were modified by the World Health Organization in 2016.<ref name="pmid27069254">Template:Cite journal The WHO criteria for polycythemia vera are specifically outlined in Table 4.</ref>

There are 3 major criteria for PV diagnosis:

1. A very high red blood cell count, which is usually identified by elevated levels of hemoglobin or hematocrit;
2. A bone marrow biopsy that shows hypercellularity and abnormalities in megakaryocytes; and
3. The presence of a mutation in the Janus kinase 2 (JAK2) gene.

A minor diagnostic feature is that patients usually have a very low level of erythropoietin (EPO), a growth factor that increases the production of red blood cells.<ref name="auto2">Template:Cite web</ref><ref name="auto">Template:Cite journal</ref> This is used to detect cases which are negative for JAK2 mutation.<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC7326849/</ref>

Reviews 2023-25

As of 2025, reviews state diagnosis can be based on

• the presence of a JAK2 mutation and
• hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women.

Bone marrow morphologic confirmation is advised but not mandated.<ref>Template:Cite journal</ref><ref name="auto3">Template:Cite book</ref>

Outlook and prognosis

Prognosis

PV may remain stable for many years, with no effect on life expectancy, particularly if managed effectively.<ref name="auto1">Template:Cite web</ref> Studies show the median survival rate of controlled PV ranges from 10 to 20 years but most observations are of people diagnosed in their 60s. Patients live close to a normal life expectancy,<ref name="auto"/> but overall survival in PV is below that of age- and sex-matched general population.<ref name="auto4">Template:Cite journal</ref> Factors predicting this may include age and detailed genetic differences.<ref name="auto4"/>

Possible complications and developments

PV may cause blood clotting complications (thrombosis),<ref>Template:Cite web</ref> with the two main risk factors being a previous clot or clots, and age (60 years or older).<ref name="auto13">Template:Cite web</ref> If PV is untreated, there is a substantial risk of Budd-Chiari syndrome (a hepatic vein thrombosis).<ref name="pmid16827884">Template:Cite journal</ref>

PV may develop into myelofibrosis (a rare bone marrow cancer) or acute myeloid leukemia.<ref name="auto1"/><ref name="auto8">Template:Cite web</ref><ref name="auto3"/>

Bleeding is a possible PV complication, although major bleeds are rare.<ref name="auto3"/>

Treatment and management

Overview

As of 2024 a cure for PV has not been found.<ref name="auto4"/><ref name="auto3"/>

The treatment goal is to prevent thrombosis.

The "backbone" of treatment, regardless of risk category, if there are no contraindications, is;

• Periodic blood withdrawals (phlebotomy), to keep hematocrit level below 45%, and
• daily (or twice daily) aspirin (81 mg).<ref name="auto4"/><ref name="auto3"/>

Additional management, depending on risks appraisal,<ref name="auto4"/><ref name="auto3"/> may include meds.<ref name="auto17">Template:Cite web</ref>

A secondary treatment goal is to alleviate symptoms, for instance of pruritus (itching).<ref name="auto4"/><ref name="auto3"/>

Blood withdrawals

Blood withdrawal, sometimes called phlebotomy or venesection, is a process similar to donating blood<ref>Template:Cite web</ref> and helps to keep haematocrit levels low. This might be done weekly initially, and less often over time.<ref name="auto17"/>

Meds

Aspirin may be taken, to reduce thrombosis risk, regardless of risk category.<ref name="auto4"/>

Other medications may be used;

• Hydroxyurea reduces adverse cell development. Side effects include a small increase in the risk of developing a leukaemia. Ruxolitinib (brand name Jakafi), a JAK2 inhibitor, and Busulfan may be used as alternatives.<ref>Template:Cite journal</ref>
• Ropeginterferon alfa-2b (Besremi) reduces the rate of blood cell production,<ref name="Besremi EPAR">Template:Cite web</ref><ref name="FDA PR 20211112">Template:Cite press release Template:PD-notice</ref><ref name="PharmaEssentia PR">Template:Cite press release</ref> and can be used regardless of treatment history.<ref name="FDA PR 20211112" /> Interferon alfa-2b is also used.<ref name=":0">Template:Cite web</ref>
• Anagrelide with other cytoreductive drugs may be used to manage platelet levels.<ref name="auto17"/><ref>Template:Cite web</ref>

Erlotinib may be an additional treatment option for those with certain genetic markers.<ref>Template:Cite journal</ref>

Allopurinol may be used to manage gout.<ref name="auto17"/>

Lifestyle

A healthy lifestyle, including no smoking and avoidance of excessive weight, is also recommended.<ref name="auto17" />

Specialist care

A hematologist may be involved in the care of patients with PV.<ref name="auto3"/>

Managing itching, if present

Ideas for managing itching include trying cooler showers and baths.<ref name="auto13"/><ref>Template:Cite web</ref>

Managing emotional and practical effects

Patient education and patient forums can help patients practically and emotionally manage a PV diagnosis, symptoms and other practical considerations.<ref name="auto8"/><ref>Template:Cite web</ref>

Epidemiology

Polycythemia vera occurs in all age groups,<ref>Template:Cite journal</ref> although the incidence increases with age. One study found the median age at diagnosis to be 60 years,<ref name="pvsg">Template:Cite journal</ref> and another that the highest incidence was in people aged 70–79 years.<ref name="olmsted">Template:Cite journal</ref> 10% of PV patients are below age 40 years.<ref name="auto4"/>

Overall incidences in population studies have been 1.9/100,000 person-years in a Minnesota study,<ref name="olmsted"/> and 1.48/100,000 person-years in an age-standardized Swedish study (n = 6281).<ref name="auto4"/> PV can impact all ethnic groups. There are slightly more cases in men than women.<ref name="auto3"/><ref name="olmsted"/>

A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008.<ref name="NEPennsylvania">Template:Cite journal</ref>

While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of JAK2 has been associated with its development.<ref name="auto5"/><ref>Template:Cite journal</ref>

Notable cases

Notable people living with PV include:

• Juan Alderete
• Will Self

Few notable deaths have been attributed to PV. Instances (all aged 56 or older) are

• Alessandro Di Fiore (1965-2021), Italian entrepreneur.
• Phyllis George (1949–2020), American sportscaster and former First Lady of Kentucky<ref>Template:Cite news</ref>
• Chet Lemon (1955-2025), American baseball player<ref name="Detroit Free Press">Template:Cite news</ref>
• Ron Miles (1963–2022), American jazz trumpeter<ref name=Harrington>Template:Cite news</ref>
• Nell Rankin (1924–2005), American mezzo-soprano<ref name="NYT">Template:Cite news</ref>

History

Figures in the discovery of and development of treatment for PV include William Osler and Louis Henri Vaquez.<ref>Template:Cite journal</ref> Historically PV was called Osler–Vaquez disease.

External links

• Polycythemia Vera at the National Heart, Lung, and Blood Institute
• Template:MerckManual