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a disorder characterized by an abnormal increase in the number of red blood cells in the blood

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/06 19:00:24」(JST)

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Polycythemia vera (PV, PCV) (also known as erythremia, primary polycythemia and polycythemia rubra vera)^[1] is a myeloproliferative blood disorder in which the bone marrow makes too many red blood cells.^[1] It may also result in the overproduction of white blood cells and platelets.

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.

Epidemiology[edit source | edit]

Polycythemia vera occurs in all age groups,^[2] although the incidence increases with age. One study found the median age at diagnosis to be 60 years,^[3] while a Mayo Clinic study in Olmsted County, Minnesota found that the highest incidence was in people aged 70–79 years.^[4] 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.^[4] A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008. ^[5]

Pathophysiology[edit source | edit]

Polycythemia vera (PCV), being a primary polycythemia, 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, PCV is associated with a low serum level of the hormone erythropoietin (EPO). Instead, PCV cells have a mutation in the tyrosine kinase (JAK2), which acts in signaling pathways of the EPO-receptor, rendering those cells hypersensitive to EPO.^[6]

Symptoms[edit source | edit]

Erythromelalgia in a patient with longstanding polycythemia vera

Patients with polycythemia vera can be asymptomatic.^[7] A classic symptom of polycythemia vera is pruritus or itching, particularly after exposure to warm water (such as when taking a bath),^[8] which may be due to abnormal histamine release^[9]^[10] or prostaglandin production.^[11] Such itching is present in approximately 40% of patients with polycythemia vera.^[3] Gouty arthritis may be present in up to 20% of patients.^[3] 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.^[12] Another possible mechanism for the development for peptic ulcer is increased histamine release and gastric hyperacidity related with polycythemia vera.

A rare but classic symptom of polycythemia vera (and the related myeloproliferative disease essential thrombocythemia) is erythromelalgia.^[13] This is a sudden, severe 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.^[14]^[15]

Patients with polycythemia vera are prone to the development of blood clots (thrombosis). A major thrombotic complication (e.g. heart attack, stroke, deep venous thrombosis, or Budd-Chiari syndrome) may sometimes be the first symptom or indication that a person has polycythemia vera.

Headaches, lack of concentration and fatigue are common symptoms that occur in patients with polycythemia vera as well.

Diagnosis[edit source | edit]

Physical exam findings are non-specific, but may include enlarged liver or spleen, plethora, or gouty nodules. The diagnosis is often suspected on the basis of laboratory tests. Common findings include an elevated hemoglobin level or hematocrit, reflecting the increased number of red blood cells; the platelet count or white blood cell count may also be increased. The erythrocyte sedimentation rate (ESR) is decreased due to an increase in zeta potential. Because polycythemia vera results from an essential increase in erythrocyte production, patients have a low erythropoietin (EPO) level.

In primary polycythemia, there may be 8 to 9 million and occasionally 11 million erythrocytes per cubic millimeter of blood (a normal range for adults is 4-6), and the hematocrit may be as high as 70 to 80%. In addition, the total blood volume sometimes increases to as much as twice normal. The entire vascular system can become markedly engorged with blood, and circulation times for blood throughout the body can increase up to twice the normal value. The increased numbers of erythrocytes can cause the viscosity of the blood to increase as much as five times normal. Capillaries can become plugged by the very viscous blood, and the flow of blood through the vessels tends to be extremely sluggish.

As a consequence of the above, people with untreated polycythemia vera are at a risk of various thrombotic events (deep venous thrombosis, pulmonary embolism), heart attack and stroke, and have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis),^[16] or myelofibrosis. The condition is considered chronic; no cure exists. Symptomatic treatment (see below) can normalize the blood count and most patients can live a normal life for years.

The disease appears more common in Jews of European extraction than in most non-Jewish populations. Some familial forms of polycythemia vera are noted, but the mode of inheritance is not clear.

Recently, in 2005, a mutation in the JAK2 kinase (V617F) was found by multiple research groups ^[17]^[18] to be strongly associated with polycythemia vera. JAK2 is a member of the Janus kinase family and makes the erythroid precursors hypersensitive to erythropoietin (EPO). This mutation may be helpful in making a diagnosis or as a target for future therapy.

Treatment[edit source | edit]

Untreated, polycythemia vera can be fatal.^[19]^[20] Research has found that the "1.5-3 years of median survival in the absence of therapy has been extended to at least 10-20 years because of new therapeutic tools."^[21]

As the condition cannot be cured, treatment focuses on treating symptoms and reducing thrombotic complications by reducing the erythrocyte levels.

Bloodletting (called venesection or phlebotomy) is one form of treatment, which often may be combined with other therapies. The removal of blood from the body reduces the blood volume and brings down the hematocrit levels; in patients with polycythemia vera, this reduces the risk of blood clots. Venesection is typically performed in people with polycythemia vera to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women.^[22] It has been observed that phlebotomy also improves cognitive impairment.^[23]

Low dose aspirin (75–81 mg daily) is often prescribed. Research has shown that aspirin reduces the risk for various thrombotic complications.

Chemotherapy for polycythemia may be used, either for maintenance, or when the rate of bloodlettings required to maintain normal hematocrit is not acceptable, or when there is significant thrombocytosis or intractable pruritus. This is usually with a "cytoreductive agent" (hydroxyurea, also known as hydroxycarbamide).

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 safer in this aspect, there is still some debate about its long-term safety.

In the past, injection of radioactive isotopes (principally phosphorus-32) was used as another means to suppress the bone marrow. Such treatment is now avoided due to a high rate of AML transformation.

Other therapies include interferon injections, and in cases where secondary thrombocytosis (high platelet count) is present, anagrelide may be prescribed.

Bone marrow transplants are rarely undertaken in polycythemia patients; since this condition is non-fatal if treated and monitored, the benefits rarely outweigh the risks involved in such a procedure.

There are indications that with certain genetic markers, erlotinib may be an additional treatment option for this condition.^[24]

Selective JAK2 inhibitors are being investigated in vitro and in clinical trials.^[25]^[26]^[27]^[28]

References[edit source | edit]

^ ^a ^b "polycythemia vera." at Encyclopædia Britannica. 2010. Encyclopædia Britannica Online. 21 Sep. 2010
^ Passamonti F, Malabarba L, Orlandi E, Baratè C, Canevari A, Brusamolino E, Bonfichi M, Arcaini L, Caberlon S, Pascutto C, Lazzarino M (2003). "Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia". Haematologica 88 (1): 13–8. PMID 12551821.
^ ^a ^b ^c Berlin NI (1975). "Diagnosis and classification of polycythemias". Semin Hematol 12: 339.
^ ^a ^b Anía B, Suman V, Sobell J, Codd M, Silverstein M, Melton L (1994). "Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989". Am J Hematol 47 (2): 89–93. doi:10.1002/ajh.2830470205. PMID 8092146.
^ MICHAEL RUBINKAM (2008). "Cancer cluster confirmed in northeast Pennsylvania". Associated Press. ^{[dead link]}
^ Kumar, et al.: Robbin's Basic Pathology, 8th edition, Saunders, 2007
^ [Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York
^ Saini KS, Patnaik MM, Tefferi A (2010). "Polycythemia vera-associated pruritus and its management". Eur J Clin Invest 40 (9): 828–34. doi:10.1111/j.1365-2362.2010.02334.x. PMID 20597963.
^ Steinman H, Kobza-Black A, Lotti T, Brunetti L, Panconesi E, Greaves M (1987). "Polycythaemia rubra vera and water-induced pruritus: blood histamine levels and cutaneous fibrinolytic activity before and after water challenge". Br J Dermatol 116 (3): 329–33. doi:10.1111/j.1365-2133.1987.tb05846.x. PMID 3567071.
^ Jackson N, Burt D, Crocker J, Boughton B (1987). "Skin mast cells in polycythaemia vera: relationship to the pathogenesis and treatment of pruritus". Br J Dermatol 116 (1): 21–9. doi:10.1111/j.1365-2133.1987.tb05787.x. PMID 3814512.
^ Fjellner B, Hägermark O (1979). "Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement". Acta Derm Venereol 59 (6): 505–12. PMID 94209.
^ Torgano G, Mandelli C, Massaro P, Abbiati C, Ponzetto A, Bertinieri G, Bogetto S, Terruzzi E, de Franchis R (2002). "Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori". Br J Haematol 117 (1): 198–202. doi:10.1046/j.1365-2141.2002.03380.x. PMID 11918555.
^ van Genderen P, Michiels J (1997). "Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera". Semin Thromb Hemost 23 (4): 357–63. doi:10.1055/s-2007-996109. PMID 9263352.
^ Michiels J (1997). "Erythromelalgia and vascular complications in polycythemia vera". Semin Thromb Hemost 23 (5): 441–54. doi:10.1055/s-2007-996121. PMID 9387203.
^ Landolfi R, Ciabattoni G, Patrignani P, Castellana M, Pogliani E, Bizzi B, Patrono C (1992). "Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo". Blood 80 (8): 1965–71. PMID 1327286.
^ Thurmes PJ, Steensma DP (July 2006). "Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis". Eur. J. Haematol. 77 (1): 57–60. doi:10.1111/j.1600-0609.2006.00667.x. PMID 16827884.
^ Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101.
^ Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005). "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis". Cancer Cell 7 (4): 387–97. doi:10.1016/j.ccr.2005.03.023. PMID 15837627.
^ Mayo Clinic staff. "Polycythemia vera - MayoClinic.com". Polycythemia vera: Definition. Mayo Clinic. Retrieved 2011-09-03.
^ "What Is Polycythemia Vera?". What Is Polycythemia Vera?. National Heart, Lung and Blood Institute. Retrieved 2011-09-03.
^ "Polycythemia Vera Follow-up". Polycythemia Vera Follow-up. Retrieved 2011-09-03.
^ Streiff MB, Smith B, Spivak JL (2002). "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 99 (4): 1144–9. doi:10.1182/blood.V99.4.1144. PMID 11830459.
^ Di Pollina L, Mulligan R, Juillerat Van der Linden A, Michel JP, Gold G (2000). "Cognitive impairment in polycythemia vera: partial reversibility upon lowering of the hematocrit". Eur. Neurol. 44 (1): 57–9. PMID 10894997.
^ Li Z, Xu M, Xing S, Ho W, Ishii T, Li Q, Fu X, Zhao Z (2007). "Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth". J Biol Chem 282 (6): 3428–32. doi:10.1074/jbc.C600277200. PMC 2096634. PMID 17178722.
^ Open Label INCB018424 in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis. ClinicalTrials.gov.
^ Verstovsek S, Manshouri T, Quintás-Cardama A, et al. (February 2008). "WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation". Clin. Cancer Res. 14 (3): 788–96. doi:10.1158/1078-0432.CCR-07-0524. PMID 18245540.
^ Wernig G, Kharas MG, Okabe R, et al. (April 2008). "Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera". Cancer Cell 13 (4): 311–20. doi:10.1016/j.ccr.2008.02.009. PMID 18394554.
^ Geron I, Abrahamsson AE, Barroga CF, et al. (April 2008). "Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors". Cancer Cell 13 (4): 321–30. doi:10.1016/j.ccr.2008.02.017. PMID 18394555.

External links[edit source | edit]

Myeloproliferative Disease Support
Myeloproliferative Disorders (CMPD Education Foundation)
MPN Research Foundation - Advancing Research, Empowering Patients
Myelo-Proliferative Disease Research Consortium
11-141d. at Merck Manual of Diagnosis and Therapy Professional Edition

UpToDate Contents

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1. 真性多血症が疑われる患者に対する診断的アプローチ diagnostic approach to the patient with suspected polycythemia vera
2. 真性多血症の予後および治療 prognosis and treatment of polycythemia vera
3. 先天性赤血球増多症および真性多血症の分子学的病因 molecular pathogenesis of congenital polycythemic disorders and polycythemia vera
4. 骨髄増殖性腫瘍の概要 overview of the myeloproliferative neoplasms
5. 赤血球増加症患者に対する診断的アプローチ diagnostic approach to the patient with polycythemia

English Journal

Nitric oxide scavenging by cell-free hemoglobin may be a primary factor determining hypertension in polycythemic patients.

Rusak T, Misztal T, Piszcz J, Tomasiak M.Author information Department of Physical Chemistry, Medical University of Bialystok , Bialystok , Poland.AbstractAbstract We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NOx) in the plasma of 73 PV patients and 38 healthy controls. The effect of isovolemic erythrocytapheresis (ECP) on the considered parameters was also studied. From the whole group of PV patients a subset of subjects with normal (normotensive patients, n = 16) and elevated MAP (hypertensive patients, n = 57) can be subtracted. It was found that in comparison with healthy controls, PV patients have significantly (p ≤ 0.01) elevated Hct (0.567 vs. 0.422), blood viscosity (5.45 vs. 3.56 cP), MAP (106.8 vs. 93.8 mmHg), plasma fHb (9.7 vs. 2.8 mg/dL), and NOx levels (34.1 vs. 27.5 μM). Compared with normotensive patients, hypertensive PV patients demonstrated a higher rise in fHb (10.2 vs. 8.0) and plasma NOx levels (35.8 vs. 31.0). In PV patients, fHb positively correlates with MAP (r = 0.489), NOx levels (r = 0.461), hematocrit (r = 0.428), and viscosity (r = 0.393). Blood viscosity positively correlated with hematocrit (r = 0.894), but not with other considered parameters. In PV patients MAP poorly correlated with hematocrit, whereas the correlation between MAP and NOx altered from - 0.325 (healthy control) to + 0.268 (PV patients). ECP procedure was associated with a significant (p < 0.01) reduction of hematocrit, fHb, blood viscosity, and MAP. In the normotensive subgroup of PV patients the ECP procedure did not affect MAP. It can be concluded that accelerated scavenging of nitric oxide by fHb rather than high Hct may be a key factor determining the development of hypertension in PV patients.
Free radical research.Free Radic Res.2014 Feb;48(2):230-8. doi: 10.3109/10715762.2013.860225. Epub 2013 Nov 25.
Abstract We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NOx) in the
PMID 24180690

Chronic myeloproliferative diseases.

de Lacerda JF1, Oliveira SN2, Ferro JM3.Author information 1Department of Hematology and Bone Marrow Transplantation, Hospital de Santa Maria, Lisbon, Portugal.2Department of Neurology, Hospital da Luz, Lisbon, Portugal.3Neurology Service, Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal. Electronic address: jmferro@fm.ul.pt.AbstractThe chronic myeloproliferative disorders are a group of diseases in which there is an increased proliferation of one or more subtypes of myeloid cells; they include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). In ET and PV the main neurologic manifestations are headaches, dizziness and macro- and microvascular, both venous and arterial, thrombosis and intracranial hemorrhages. Paresthesias and chorea also occur in PV. In PMF neurologic complications are very rare and consist predominantly of spinal cord compression by extramedullary hematopoiesis tissue.
Handbook of clinical neurology.Handb Clin Neurol.2014;120:1073-81. doi: 10.1016/B978-0-7020-4087-0.00072-3.
The chronic myeloproliferative disorders are a group of diseases in which there is an increased proliferation of one or more subtypes of myeloid cells; they include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). In ET and PV the main neurologic manifestation
PMID 24365372

Coexistence of renal artery stenosis, primary antiphospholipid syndrome and polycythaemia vera: an exceptional association.

Ha-Ou-Nou FZ, Boumzebra D, Essaadouni L.Author information Department of Internal Medicine, Department of Cardiovascular Surgery, University Hospital Mohammed VI, Marrakech, Morocco.AbstractRenal artery stenosis is the narrowing of the renal artery which causes hypertension and atrophy of the affected kidney, ultimately leading to renal failure if not treated and most often caused by atherosclerosis or fibromuscular dysplasia. Recently, renal artery stenosis has also been documented in patients with the antiphospholipid syndrome and in very few cases with myeloproliferative disease. In this paper, we describe a 31-year-old female with a history of gangrene affecting the toes with severe hypertension (200/110 mmHg), whose investigations revealed a combination of renal artery stenosis, primary antiphospholipid syndrome and polycythaemia vera.
Lupus.Lupus.2014;23(1):84-7. doi: 10.1177/0961203313512010. Epub 2013 Nov 6.
Renal artery stenosis is the narrowing of the renal artery which causes hypertension and atrophy of the affected kidney, ultimately leading to renal failure if not treated and most often caused by atherosclerosis or fibromuscular dysplasia. Recently, renal artery stenosis has also been documented in
PMID 24197551

Japanese Journal

Polycythemia Vera Terminating in Refractory Ascites

Toyama Kohtaro,Mitsui Takeki,Yokohama Akihiko [他]
北関東医学 62(2), 159-162, 2012-05
… A 64-year-old woman,with more than a 20 year history of polycythemia vera(PV),developed portalhypertension,myelofibrosis and extramedullary hematopoiesis accompanied by massive ascites. …
NAID 40019329479

真性赤血球増加症の病態と治療 (造血器腫瘍学 : 基礎と臨床の最新研究動向) -- (骨髄系腫瘍の臨床)

小松規夫
日本臨床 70 (1018 増刊2), 314-320, 2012-04
NAID 40019281854

Related Pictures

★リンクテーブル★

リンク元	「真性多血症」「深部静脈血栓症」「オスラー病」「赤血病」「PCV」

「真性多血症」

Polycythemia vera
	Classification and external resources
	; Blood smear from a patient with polycythemia vera
ICD-10	D45
ICD-9	238.4
ICD-O:	M9950/3
MedlinePlus	000589
MeSH	D011087

　　[★]

poly(多) + cyt(細胞) + mia(血症) vera(真性？)
ラ: polycythemia vera PCV PV
同: 真性赤血球増加症、真性赤血球増多症; オスラー病 Osler disease，オスラー・ワーケ病オスラー-ヴァケー病 Osler-Vaquez disease，ヴァケー病 Vaquez disease
関: 骨髄増殖性疾患(MPD)

概念

慢性骨髄増殖性疾患の一つ。
多能性血液幹細胞の腫瘍性増殖により、赤血球数の絶対的増加と循環赤血球量の増加を呈する。
赤血球の他に、白血球、血小板も増加するが、リンパ球は増加しない。

病因

多能性幹細胞の異常により、血球が腫瘍性に増殖することが原因とされる。

疫学

新患発生数：100万人対2人/年
50-60歳に多い。

症状

循環赤血球量の増加　→　循環血液量の増加＋血液粘稠度の亢進：循環障害による頭痛、めまい、耳鳴り、倦怠感、知覚異常、呼吸困難など　→　高血圧、狭心症・心筋梗塞、間欠性跛行
血球の増加：脾腫(70%の症例)、赤ら顔(口唇、頬部、鼻尖、耳)　→肝臓や脾臓の腫大は髄外造血による
骨髄

ヒスタミンの放出：皮膚の掻痒感、消化性潰瘍
尿酸の放出増加：高尿酸血症　→　痛風

代謝亢進：発汗、体重減少

検査

血算

赤血球：増加
白血球：増加
血小板：増加
リンパ球：正常

血液生化学

血清尿酸：高値
血清ヒスタミン：高値
血清ビタミンB12：高値　　→　顆粒球増加
エリスロポエチン：低値　　→　二次性ではない
血清鉄：低値
血清フェリチン：低値
好中球アルカリホスファターゼ染色(NAPスコア)：上昇　⇔　慢性骨髄性白血病：低下
SpO2 ：正常

遺伝子検査

JAK2 V617F遺伝子変異解析：骨髄増殖性腫瘍である真性多血症・本態性血小板血症・原発性骨髄線維症の患者においてみられるJAK2遺伝子の変異を検出する。JAK2遺伝子のV617F変異は、骨髄増殖性腫瘍のうち真性多血症の患者の97%、原発性骨髄線維症の患者の50-60%、本態性血小板血症の患者の55-65%にみられる変異である。

特殊検査

循環赤血球量：増加(男性36 mL/kg以上、女性32 mL/kg以上)　←　RIを使うはず

骨髄穿刺

過形成
NAP score：増加

骨髄生検

過形成

鉄代謝

PIDT 1/2：低下　　←　　血漿中から骨髄へのFe移動が亢進
%RCU：上昇　　←　　投与された鉄はほとんどが赤血球に分布

診断

循環赤血球量の増加、動脈酸素飽和度が正常であること、脾腫の存在
血小板数の増加、白血球数の増加、白血球アルカリホスファターゼ値の上昇、血清ビタミンB12の高値
血中、尿中のエリスロポエチン値はむしろ低下
受容体の質的異常・量的異常が認められない

インスリン様成長因子Iに対する感受性の亢進、Bcl-2ファミリーに属するBcl-XLの発現亢進、エリスロポエチン受容体の発現パターンの異常、トロンボポエチン受容体の発現低下、チロシンホスファターゼの発現異常、エリスロポエチン受容体遺伝子の異常

診断基準

http://www.med.osaka-cu.ac.jp/labmed/page080.html

2008年WHOによる真性多血症診断基準
大基準	1.　Hb>18.5g/dl(男性）、>16.5/dl（女性）もしくは　年齢、性別、住居している緯度から換算したHbかHtが9.9％以上増加しているもしくは　Hb>17g/dl(男性）、>15g/dl（女性）で鉄欠乏性貧血などの改善以外にHbが本人の基準値よりも2g/dl以上持続上昇しているもしくは　赤血球数が予想値の25％を超えて上昇している
	2. Jak2V617Fかもしくは同様の変異が存在する
小基準	1.　骨髄の3系統が増生を示す
	2.　血清エリスロポイエチンがおおよそ正常値を示す
	3.　内因性の赤芽球コロニー形成を認める

鑑別診断

治療

治療目標：生命予後は良好であり、10年生存率は50%異常が期待できる。合併症となる血栓症の予防が主眼となる。

瀉血：Ht 42-47%　←　血管閉塞症の頻度が低下する

血圧や脈拍の経過を見ながら月1-2回、1回200-400ml程度で行う。

高齢者や心血管障害を有する例では1回100-200ml頻回の瀉血が望ましい

抗血栓療法：血栓症の既往、もしくはリスクが高いときには抗血小板薬を処方。
抗癌薬投与：ヒドロキシウレアが第一選択で、不応例や不耐例の場合はルキソリチニブ。以前は40歳以上ではブスルファンとされていた。
放射性同位体：32P
高尿酸血症を有する場合にはフェブリクやアロプリノールを処方。

血栓症リスク

Barbui T, et al.（J Clin Oncol. 2011 ; 29 : 761）

リスク分類	予後因子
低リスク	年齢＜60歳、かつ血栓症の既往なし
高リスク	年齢≧60歳、または血栓症の既往がある

予後

生存は平均6-10年。5年生存率約75%, 10年生存率約55%
主な死因は、消化管出血や脳血管障害

長期生存

25%の症例で骨髄線維症へ移行
まれに急性白血病を発症。32Pによる治療を受けた患者に多い

USMLE

Q book p.245 32
first aid step1 2006 p.278

国試

101A033

参考

総論 - 造血器腫瘍診療ガイドライン - 造血器腫瘍診療ガイドライン

http://www.jshem.or.jp/gui-hemali/1_4.html#soron

PV瀉血療法後のHt目標値を45％にすることは勧められるか

http://www.jshem.or.jp/gui-hemali/1_4.html#cq7

真性多血症の治療ガイド - ノバルティスファーマ株式会社

http://product.novartis.co.jp/jak/tool/JAK00193GG0002.pdf

「深部静脈血栓症」

　　[★]

英: deep venous thrombosis DVT, deep vein thrombosis
同: 深部静脈血栓、静脈血栓症
関: 末梢静脈疾患、下肢深部静脈血栓症

概念

深部静脈(特に下肢)に血栓が生じる
静脈血栓により生じた肺塞栓は静脈血栓塞栓症(venous thromboembolism VTE)とよばれる

リスクファクター

リスク評価はWells scoreを使う。

PHD.366

血流うっ滞

安静：手術、乗り物(飛行機、車)
四肢の固定：following bone fraction
心不全：全身性静脈うっ血
hyperviscosity syndrome：polycythemia vera

血液凝固亢進

遺伝性凝固障害

resistance to activated protein C(factor V Leiden)
変異プロトロンビン遺伝子(PT G20210A)
antithrombin III deficiency
deficiency of protein C/deficiency of protein S

抗リン脂質抗体、ループスアンチコアグラント
悪性腫瘍
妊娠/経口避妊薬　→　late pregnancy and early pospartum period：胎児がIVCを圧迫。エストロゲンによる凝固傾向。
MPD
喫煙

血管損傷

外傷
instrumentation

SAN.378

1. 基礎疾患・素因

血栓性素因
静脈血栓症の既往
肺塞栓症の既往
年齢(60歳以上)
長期臥床(4日以上)
肥満(肥満度BMI25以上)
悪性腫瘍

下肢静脈瘤

下肢、骨盤骨折

多発外傷

骨盤部腫瘤の合併
片麻痺、四肢麻痺

2. 手術因子

全身麻酔
3時間以上の手術
開腹術
人工股関節置換術、膝関節置換術
気腹手術、開腹下骨盤手術
静脈還流を阻害する体位(骨盤低位、側臥位など)

3. その他の因子

妊娠
経口避妊薬服用
副腎皮質ホルモン服用

血栓性素因：後天性抗リン脂質抗体症候群、先天性アンチトロンビン欠損、プロテインC欠損、プロテインS欠損、第V因子異常、プラスミノゲン以上、異常フィブリノゲン血症、第XII因子欠損、組織プラスミノゲン活性化因子インヒビタ増加、トロンボモジュリン異常など

参考2

疾患別に見るとDVTでもPTEでも卵巣癌が最多で、子宮体癌がこれに次ぐ。術前発症では卵巣癌が最多である。卵巣癌の術前にDVTがおおいのは多量腹水による脱水、自宅での安静、腫瘍細胞数が非常に多い、腫瘍細胞が放出する組織因子が多いなどによる。卵巣後の術後では、根治術では手術時間が長く、侵襲度が高い、リンパ節郭清を要する、多量の輸血が必要なことが多い、また長期にわたる化学療法を要するなどによる。

リスク評価

ＤＶＴの検査前確率

＞大項目

活動性の癌
麻痺、足が動かない
ベット上臥床(＞3日)、または大手術(＜4週)
静脈に沿い限局した疼痛
大腿/腓腹筋の腫脹
無症状側と比較して＞3cmの腓腹筋腫脹
ＤＶＴの家族歴(第一度近親者で≧2人)

＞小項目

60日以内の症状ある足への外傷
有症状の下肢における圧痕性浮腫
有症状の下肢のみの表在静脈拡張
最近6ヶ月以内の入院
紅斑

高確率85%

大項目≧3+他の診断なし
大項目≧2+小項目≧2+他の診断なし

中等度の確率33%

確率が高くも低くもない

低確率5%

大項目１＋小項目≧２＋他の診断あり
大項目１＋小項目≧１＋他の診断なし
大項目０＋小項目≧３＋他の診断あり
大項目０＋小項目≧２＋他の診断なし

身体所見

evidence-based physical diagnosis 3rd edition p.473

予防

産婦人科

参考2

早期離床、ベッド上での下肢挙上・膝の屈伸・足の背屈運動、弾性ストッキング着用、間欠的空気圧迫法、脱水予防
未分画ヘパリン5,000単位を術後6～12時間以内に(止血を確認できたら術直後からでも可)1日2回皮下注/静注、3-5日投与

ガイドライン

肺血栓塞栓症および深部静脈血栓症の診断、治療、予防に関するガイドライン（2009年改訂版）

http://www.j-circ.or.jp/guideline/pdf/JCS2009_andoh_h.pdf

参考

産婦人科

1. 学際領域の診療 Interdisciplinary Practice 肺血栓塞栓症・深部静脈血栓症 - 日産婦誌

http://www.jsog.or.jp/PDF/56/5610-382.pdf

2. E．婦人科疾患の診断・治療・管理 10．10）深部静脈血栓症・肺塞栓症 - 日産婦誌61巻11号

http://www.jsog.or.jp/PDF/61/6111-591.pdf

「オスラー病」

　　[★]

英: Osler's disease, Osler disease
同: Osler病、telangiectasis hereditaria haemorrhagica
関: 遺伝性出血性毛細血管拡張症、遺伝性出血性毛細血管拡張、Osler hemorrhagic telangiectasia syndrome

同: Osler病、真性多血症 polycythemia vera

「赤血病」

　　[★]

英: erythremia
同: ディ・グリエルモ病 Di Guglielmo disease、赤血病性骨髄症 erythremic myelosis
関: 真性多血症 polycythemia vera

、赤白血病

赤芽球の異常増殖

「PCV」

　　[★]

圧制御換気 pressure-controlled ventilation
フェノキシメチルペニシリン phenoxymethylpenicillin = ペニシリン V penicillin V
真性多血症 polycythemia vera

[britannica.com-1] "polycythemia vera." at Encyclopædia Britannica. 2010. Encyclopædia Britannica Online. 21 Sep. 2010

[2] Passamonti F, Malabarba L, Orlandi E, Baratè C, Canevari A, Brusamolino E, Bonfichi M, Arcaini L, Caberlon S, Pascutto C, Lazzarino M (2003). "Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia". Haematologica 88 (1): 13–8. PMID 12551821.

[pvsg-3] Berlin NI (1975). "Diagnosis and classification of polycythemias". Semin Hematol 12: 339.

[olmsted-4] Anía B, Suman V, Sobell J, Codd M, Silverstein M, Melton L (1994). "Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989". Am J Hematol 47 (2): 89–93. doi:10.1002/ajh.2830470205. PMID 8092146.

[NEPennsylvania-5] MICHAEL RUBINKAM (2008). "Cancer cluster confirmed in northeast Pennsylvania". Associated Press. ^{[dead link]}

[6] Kumar, et al.: Robbin's Basic Pathology, 8th edition, Saunders, 2007

[7] [Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York

[8] Saini KS, Patnaik MM, Tefferi A (2010). "Polycythemia vera-associated pruritus and its management". Eur J Clin Invest 40 (9): 828–34. doi:10.1111/j.1365-2362.2010.02334.x. PMID 20597963.

[9] Steinman H, Kobza-Black A, Lotti T, Brunetti L, Panconesi E, Greaves M (1987). "Polycythaemia rubra vera and water-induced pruritus: blood histamine levels and cutaneous fibrinolytic activity before and after water challenge". Br J Dermatol 116 (3): 329–33. doi:10.1111/j.1365-2133.1987.tb05846.x. PMID 3567071.

[10] Jackson N, Burt D, Crocker J, Boughton B (1987). "Skin mast cells in polycythaemia vera: relationship to the pathogenesis and treatment of pruritus". Br J Dermatol 116 (1): 21–9. doi:10.1111/j.1365-2133.1987.tb05787.x. PMID 3814512.

[11] Fjellner B, Hägermark O (1979). "Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement". Acta Derm Venereol 59 (6): 505–12. PMID 94209.

[12] Torgano G, Mandelli C, Massaro P, Abbiati C, Ponzetto A, Bertinieri G, Bogetto S, Terruzzi E, de Franchis R (2002). "Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori". Br J Haematol 117 (1): 198–202. doi:10.1046/j.1365-2141.2002.03380.x. PMID 11918555.

[13] van Genderen P, Michiels J (1997). "Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera". Semin Thromb Hemost 23 (4): 357–63. doi:10.1055/s-2007-996109. PMID 9263352.

[14] Michiels J (1997). "Erythromelalgia and vascular complications in polycythemia vera". Semin Thromb Hemost 23 (5): 441–54. doi:10.1055/s-2007-996121. PMID 9387203.

[15] Landolfi R, Ciabattoni G, Patrignani P, Castellana M, Pogliani E, Bizzi B, Patrono C (1992). "Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo". Blood 80 (8): 1965–71. PMID 1327286.

[pmid16827884-16] Thurmes PJ, Steensma DP (July 2006). "Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis". Eur. J. Haematol. 77 (1): 57–60. doi:10.1111/j.1600-0609.2006.00667.x. PMID 16827884.

[17] Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101.

[18] Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005). "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis". Cancer Cell 7 (4): 387–97. doi:10.1016/j.ccr.2005.03.023. PMID 15837627.

[19] Mayo Clinic staff. "Polycythemia vera - MayoClinic.com". Polycythemia vera: Definition. Mayo Clinic. Retrieved 2011-09-03.

[20] "What Is Polycythemia Vera?". What Is Polycythemia Vera?. National Heart, Lung and Blood Institute. Retrieved 2011-09-03.

[21] "Polycythemia Vera Follow-up". Polycythemia Vera Follow-up. Retrieved 2011-09-03.

[22] Streiff MB, Smith B, Spivak JL (2002). "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 99 (4): 1144–9. doi:10.1182/blood.V99.4.1144. PMID 11830459.

[23] Di Pollina L, Mulligan R, Juillerat Van der Linden A, Michel JP, Gold G (2000). "Cognitive impairment in polycythemia vera: partial reversibility upon lowering of the hematocrit". Eur. Neurol. 44 (1): 57–9. PMID 10894997.

[24] Li Z, Xu M, Xing S, Ho W, Ishii T, Li Q, Fu X, Zhao Z (2007). "Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth". J Biol Chem 282 (6): 3428–32. doi:10.1074/jbc.C600277200. PMC 2096634. PMID 17178722.

[25] Open Label INCB018424 in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis. ClinicalTrials.gov.

[pmid18245540-26] Verstovsek S, Manshouri T, Quintás-Cardama A, et al. (February 2008). "WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation". Clin. Cancer Res. 14 (3): 788–96. doi:10.1158/1078-0432.CCR-07-0524. PMID 18245540.

[pmid18394554-27] Wernig G, Kharas MG, Okabe R, et al. (April 2008). "Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera". Cancer Cell 13 (4): 311–20. doi:10.1016/j.ccr.2008.02.009. PMID 18394554.

[pmid18394555-28] Geron I, Abrahamsson AE, Barroga CF, et al. (April 2008). "Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors". Cancer Cell 13 (4): 321–30. doi:10.1016/j.ccr.2008.02.017. PMID 18394555.

Polycythemia vera
Classification and external resources
Blood smear from a patient with polycythemia vera
ICD-10	D45
ICD-9	238.4
ICD-O:	M9950/3
MedlinePlus	000589
MeSH	D011087

匿名

検索

案内

polycythemia vera

WordNet

Wikipedia preview

wiki en

Contents

Epidemiology[edit source | edit]

Pathophysiology[edit source | edit]

Symptoms[edit source | edit]

Diagnosis[edit source | edit]

Treatment[edit source | edit]

See also[edit source | edit]

References[edit source | edit]

External links[edit source | edit]

UpToDate Contents

English Journal

Japanese Journal

Related Links

Related Pictures

★リンクテーブル★

「真性多血症」

概念

病因

疫学

症状

検査

血算

血液生化学

遺伝子検査

特殊検査

骨髄穿刺

骨髄生検

鉄代謝

診断

診断基準

鑑別診断

治療

血栓症リスク

予後

長期生存

USMLE

国試

参考

「深部静脈血栓症」

概念

リスクファクター

PHD.366

SAN.378

リスク評価

ＤＶＴの検査前確率

高確率85%

中等度の確率33%

低確率5%

身体所見

予防

産婦人科

ガイドライン

参考

産婦人科

「オスラー病」

「赤血病」

「PCV」