Polycythemia vera

"Erythremia" redirects here. For similar-sounding medical terms, see arrythmia and erythema.
Polycythemia vera
Other namesPolycythaemia vera (PV, PCV), erythremia, primary polycythemia, Vaquez disease, Osler-Vaquez disease, polycythemia rubra vera[1]
Blood smear from a patient with polycythemia vera
SpecialtyOncology, hematology

In oncology, polycythemia vera (PV) is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells.[1] The majority of cases[2] are caused by mutations in the JAK2 gene, most commonly resulting in a single amino acid change in its protein product from valine to phenylalanine at position 617.[3]

Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the increased red blood cells. It is more common in the elderly and may be symptomatic or asymptomatic. Common signs and symptoms include itching (pruritus), and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin. Patients with polycythemia vera are more likely to have gouty arthritis. Treatment consists primarily of phlebotomy as well as oral chemotherapy and emerging treatments like long-acting interferon formulations.

Signs and symptoms

Erythromelalgia is a rare symptom of PV, here present in a patient with longstanding polycythemia vera. Note reddish limbs and swelling.

People with polycythemia vera can be asymptomatic.[4] Clinical symptoms of polycythemia vera are mostly due to hyperviscosity of blood. A classic symptom of polycythemia vera is pruritus or itching, particularly after exposure to warm water (such as when taking a bath),[5] which may be due to abnormal histamine release[6][7] or prostaglandin production.[8] Such itching is present in approximately 40% of patients with polycythemia vera.[9] Gouty arthritis may be present in up to 20% of patients.[9] Peptic ulcer disease is also common in patients with polycythemia vera; most likely due to increased histamine from mast cells, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium H. pylori.[10]

A classic symptom of polycythemia vera (and the related myeloproliferative disease essential thrombocythemia) is erythromelalgia.[11] This is 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.[12][13] Splenomegaly may cause the spleen to be palpable in some patients, which has been reported by Lee et al. (2022) to be associated with both the V617F mutation and the development of myelofibrosis.[14]

Pathophysiology

Polycythemia vera (PV), being a primary polycythemia (increase in the fraction of volume occupied by red cells in the blood), is caused by neoplastic proliferation and maturation of erythroid, megakaryocytic and granulocytic elements to produce what is referred to as panmyelosis. In contrast to secondary polycythemias, PV is associated with a low serum level of the hormone erythropoietin (EPO). Instead, PV cells often carry activating mutation in a tyrosine kinase–encoding gene, JAK2, which acts in signaling pathways of the EPO receptor, making those cells proliferate independently from EPO.[15][page needed]

Diagnosis

Diagnostic criteria for polycythemia vera were modified by the World Health Organization in 2016.[16] The WHO criteria for polycythemia vera are specifically outlined in Table 4, and emphasis is given to accurate histological observations as proven predictors in the prognosis of the disease.

As summarized by Verstovek following the 2016 European Hematology Association Congress,[17] there are 3 major criteria for PV diagnosis:

  1. The first is 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.

Patients usually have a very low level of erythropoietin, a growth factor that increases the production of red blood cells, which may be considered a minor diagnostic feature.

A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera.[18][19] While it is a JAK2 V617F mutation in 95% of patients, JAK2 exon 12 mutations have also been observed.[20] The V617F mutation is not inherited, but develops as a somatic mutation in the erythroid progenitor cells.[21] Some patients may lose the normal allele in the diseased cells entirely together with the short arm of chromosome 9 (9p), likely due to mitotic recombination causing copy-neutral loss of heterozygosity.[22] While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of JAK2 has been associated with its development.[23][24]

People with untreated polycythemia vera have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis).[25]

Treatment

Untreated, polycythemia vera can be fatal, with the median survival in patients being 1.5-3 years.[26][27][28] Data on the effect of life-span of an individual with treated polycythemia vera is inconclusive due to the rarity of the disease. Studies show the median survival rate of controlled Polycythemia Vera ranges from 10 to 20 years; however, most observations are of people diagnosed in their 60s. Patients live close to a normal life expectancy.[29]

Frequent blood withdrawals (phlebotomy) are one form of treatment, which often may be combined with other therapies. The removal of blood from the body induces iron deficiency, thereby decreasing the hemoglobin / hematocrit level, and reducing the risk of blood clots. Phlebotomy is typically performed to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women.[30] It has been observed that phlebotomy also reduces cognitive impairment.[31]

Medications are also used which reduce the number of red blood cells. These include hydroxyurea and interferon therapy, among others.[32] The tendency of some practitioners to avoid chemotherapy if possible, especially in young patients, is a result of research indicating possible increased risk of transformation to acute myelogenous leukemia (AML). While hydroxyurea is considered a safer chemotherapy in this aspect, there is still some debate about its long-term safety.[33]

There are indications that the lung cancer drug erlotinib may be an additional treatment option for those with certain genetic markers.[34]

Ruxolitinib (brand name Jakafi), a Janus kinase 2 (JAK2) inhibitor, is also used to treat polycythemia.[35]

Ropeginterferon alfa-2b (Besremi) was approved for medical use in the European Union in February 2019,[36] and in the United States in November 2021.[37][38] Ropeginterferon alfa-2b is the first medication approved by the U.S. Food and Drug Administration (FDA) to treat polycythemia vera that peo

Epidemiology

Polycythemia vera occurs in all age groups,[39] although the incidence increases with age. One study found the median age at diagnosis to be 60 years,[9] while a Mayo Clinic study in Olmsted County, Minnesota found that the highest incidence was in people aged 70–79 years.[40] The overall incidence in the Minnesota population was 1.9 per 100,000 person-years, and the disease was more common in men than women.[40] A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008.[41]

Notable deaths

References

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  2. ^ Tefferi A, Lasho TL, Guglielmelli P, Finke CM, Rotunno G, Elala Y, et al. (2016). "Targeted deep sequencing in polycythemia vera and essential thrombocytopenia". Blood Advances. 1 (1): 21–30. doi:10.1182/bloodadvances.2016000216. PMC 5744051. PMID 29296692.
  3. ^ Regimbeau M, Mary R, Hermetet F, Girodon F (2022). "Genetic Background of Polycythemia Vera". Genes. 13 (4). doi:10.3390/genes13040637. PMC 9027017. PMID 35456443. Art. No. 637.
  4. ^ [Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York
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  38. ^ "U.S. FDA Approves Besremi (ropeginterferon alfa-2b-njft) as the Only Interferon for Adults With Polycythemia Vera" (Press release). PharmaEssentia. 12 November 2021. Retrieved 14 November 2021 – via Business Wire.
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Elongated front teeth of certain mammal species For other uses, see Tusk (disambiguation). An African elephant in Tanzania, with visible tusks Tusks are elongated, continuously growing front teeth that protrude well beyond the mouth of certain mammal species. They are most commonly canine teeth, as with narwhals, chevrotains, musk deer, water deer, muntjac, pigs, peccaries, hippopotamuses and walruses, or, in the case of elephants, elongated incisors. Tusks share common features such as extra...

 

 

Madeley, Staffordshire

For other places with the same name, see Madeley. Human settlement in EnglandMadeleyMadeley Mill and PoolMadeleyLocation within StaffordshirePopulation4,222 (2011)OS grid referenceSJ773443DistrictNewcastle-under-LymeShire countyStaffordshireRegionWest MidlandsCountryEnglandSovereign stateUnited KingdomPost townCrewePostcode districtCW3Dialling code01782PoliceStaffordshireFireStaffordshireAmbulanceWest Midlands UK ParliamentStone List of places UK Englan...

 

 

Dogs with Jobs

Canadian documentary television series Dogs with JobsGenreDocumentaryDeveloped by Merrily Weisbord Kim Kachanoff Written by Sara Gilbert Maura Kealey Shelley Tepperman Jon Kalina Directed by Serge Marcil Susan Mawhood Eli Gorn Ole Gjerstad Ramelle Mair Narrated by Jon Kalina John Ralston Theme music composer Lance Neveu Mathieu Vanasse Country of originCanadaNo. of seasons5No. of episodes65ProductionExecutive producers Glen Salzman David York Katherine Buck Andre Barro Producers Maura Kealey ...

2012–13 Barangay Ginebra San Miguel season

This article's lead section may be too short to adequately summarize the key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (September 2012) Basketball team season2012–13 Barangay Ginebra San Miguel seasonHead coachSiot Tanquincen (September–December 2012)Alfrancis Chua (January–July 2013)Ato Agustin (July 2013–present)Owner(s)Ginebra San Miguel, Inc. (a San Miguel Corporation subsidiary)Philippine Cup re...

 

 

2009 en Lorraine

Chronologies Données clés 2006 2007 2008  2009  2010 2011 2012Décennies :1970 1980 1990  2000  2010 2020 2030Siècles :XIXe XXe  XXIe  XXIIe XXIIIeMillénaires :Ier IIe  IIIe  Chronologies géographiques Afrique Afrique du Sud, Algérie, Angola, Bénin, Botswana, Burkina Faso, Burundi, Cameroun, Cap-Vert, Centrafrique, Comores, République du Congo, République démocratique du Congo, Côte d'Ivoire, Djibouti, Égypte, Érythrée, Éth...

 

 

Strategi Solo vs Squad di Free Fire: Cara Menang Mudah!