An increase in red cell mass is the primary feature of polycythemia vera (PV) [4] [8] [10]. Bone marrow analysis, however, shows a proliferation of all three myeloid lines: erythrocytes, granulocytes and platelets. The onset of polycythemia vera is often insidious. Early symptoms are related to blood hyperviscosity due to polycythemia. Decreased blood flow and thrombosis result in hypoxia [8] [10] [11]. Patients often present with either arterial or venous vascular occlusive events [10].

Presenting non-specific symptoms of polycythemia vera are related to hypoxia and include [10]:

• Headache
• Dizziness
• Visual impairment
• Tinnitus
• Angina pectoris

The signs and symptoms found in individuals diagnosed with polycythemia vera include [9] [10]:

• Elevated red blood cell mass >25%
• Erythrocytosis, hematocrit >60 males, >56 females
• Leukocytosis >10.9/ml
• Thrombocytosis, platelet count >400,000/ml
• Splenomegaly and splenic infract
• Thrombotic and hemorrhagic complications
• Vasomotor disturbances
• Pruritus
• Elevated Vitamin B12 level
• Plethora, a ruddy complexion of face, palms, nail beds, mucosa, and conjunctiva, due to the increased total red blood cell count.

Thrombosis and bleeding are frequent in persons with polycythemia vera. These complications are the result of the increased red blood cell count and elevated platelet count [9] [10] [19]. Bleeding is seen in approximately 1% of patients, epistaxis, gum bleeding, ecchymoses, and gastrointestinal (GI) bleeding [8] [10]. Peptic ulcer disease occurs with polycythemia vera due to increased histamine levels and resulting gastric acidity. This causes abdominal pain, abnormal feeling of fullness, and anorexia. Weight loss may result [9].

Erythromelalgia is a syndrome specific to polycythemia vera. It increases the risk of thrombosis. The symptoms are burning pain in the feet, hands, toes and fingers, sometimes associated with pallor, erythema, or cyanosis. Occasionally, it progresses to gangrene. This can be treated with aspirin (50-300 mg/d) and dipyridamole (75 mg orally 3 times a day) [11] [15].

Pruritus also results from increased histamine levels due to increased basophils and mast cells. This occurs in up to 40% of patients with polycythemia vera [9]. Splenomegaly is present in 75% of patients at the time of diagnosis, hepatomegaly in approximately 30% of patients [10] [16].

• Splenomegaly

  Splenomegaly Massive splenomegaly is the most difficult complication of polycythemia vera to manage, since it is usually refractory to chemotherapy and not durably alleviated by irradiation. [cancertherapyadvisor.com]

  During multivariable analysis, leukocytosis ⩾15 × 10 9 /l, palpable splenomegaly and ⩾grade 1 BM reticulin fibrosis remained significant. [ncbi.nlm.nih.gov]

  Patient demographics, laboratory data, and the presence of splenomegaly by disease feature including known HU use, known phlebotomy requirements, and the presence of splenomegaly were thoroughly assessed. [medpagetoday.com]

• Palpable Spleen

  A ≥50% palpable spleen length reduction was observed at any time during therapy in 20/32 evaluable patients. [ncbi.nlm.nih.gov]

  Polycythemia Vera Signs and symptoms Symptoms related to expanded blood volume and increased viscosity Headache, tinnitus, dizziness, blurred vision, TIAs, and fatigue Generalized pruritus (aquagenic) Engorged retinal veins Palpable spleen (75%) Thrombosis [slideshare.net]

  spleen N (%) 16 (55) 14 (42) 0.316 Cardiovascular risk factors N (%) 16 (53) 20 (57) 0.758 Previous thrombosis N (%) 5 (17) 9 (26) 0.376 Globally, 87% of the patients treated with peg-INF responded (26/30), with a CR rate of 70% (21/30). [jhoonline.biomedcentral.com]

  spleen length by the same time. [targetedonc.com]

• Pain

  […] feet chest pain sweating increased cough coughing up blood Cardiopulmonary problem symptoms dizziness headaches pressure in the head shortness of breath weakness and fatigue pain in hands or feet visual disturbances Irritated skin symptoms itching, especially [uihc.org]

  […] walking, pain relief with resting and reproduce with walking in a same distance. [medicaljoyworks.com]

  Blood clots in the liver and spleen can cause sudden, intense pain. Slowed blood flow also prevents enough oxygen-rich blood from reaching your organs. This can lead to angina (chest pain or discomfort) and heart failure. [hoacny.com]

  This case provides additional evidence to the data for HBO2 use in ischemic pain management. [ncbi.nlm.nih.gov]

  […] to enlarged spleen) Headache Itchiness, especially after a warm bath Red skin coloring, especially of the face Shortness of breath Symptoms of blood clots in veins near the skin surface (phlebitis) Vision problems Ringing in the ears (tinnitus) Joint pain [mountsinai.org]

• Fatigue

  Symptoms include lack of energy (fatigue) or weakness, headaches, dizziness, shortness of breath, visual disturbances, nose bleeds, bleeding gums, heavy menstrual periods, and bruising. [hopkinsmedicine.org]

  […] or swelling in arms or legs shortness of breath ruddy color in the face, hands, and feet chest pain sweating increased cough coughing up blood Cardiopulmonary problem symptoms dizziness headaches pressure in the head shortness of breath weakness and fatigue [uihc.org]

  Moreover, he has felt chronically fatigued and has lost 10 pounds without dieting or changing his appetite. He currently takes metformin and his most recent hemoglobin A1c was 6.5%. [step1.medbullets.com]

  Patients on the MPN-10 TSS validation study were slightly older than those on the fatigue survey (mean [deviation {SD}], 61.8 [12.7] years v 59.7 [11.3] years; P = .003), and a higher proportion of patients on the validation study than on the fatigue [jco.ascopubs.org]

• Weakness

  Headache, weakness, sweating, itching after a warm bath, and dizziness are all symptoms. How Is The Diagnosis Of Polycythemia Vera Made? Diagnosis may be made from a combination of a physical exam, certain blood tests, and a bone marrow biopsy. [illinoiscancercare.com]

  Symptoms include lack of energy (fatigue) or weakness, headaches, dizziness, shortness of breath, visual disturbances, nose bleeds, bleeding gums, heavy menstrual periods, and bruising. [hopkinsmedicine.org]

  Weak recommendations use "consider" or "suggested" phrasing. Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. [dynamed.com]

  […] or legs pain or swelling in arms or legs shortness of breath ruddy color in the face, hands, and feet chest pain sweating increased cough coughing up blood Cardiopulmonary problem symptoms dizziness headaches pressure in the head shortness of breath weakness [uihc.org]

• Weight Loss

  Palpable splenomegaly is one of the worst offenders since it contributes to early satiety, bloating, pain, portal hypertension, weight loss, and exacerbation of cytopenia. [medpagetoday.com]

  This is especially true for cytokine-driven items (night sweats, bone pain, weight loss) and abdominal-related complaints (abdominal discomfort, weight loss) in patients in the PV-HU subgroup. [jco.ascopubs.org]

  Hydroxycarbamide If your platelet count is high or you have other symptoms such as weight loss or sweats, you may be given tablets called hydroxycarbamide (or hydroxyurea) to take. [bloodwise.org.uk]

  Headaches Double vision or seeing dark or blind spots that come and go Itching all over the body, especially after being in warm or hot water Reddened face that looks like a blush or sunburn Weakness Dizziness Weight loss for no known reason [seattlecca.org]

  […] of phlebotomy/cytoreduction treatment for erythrocytosis Leukoerythroblastic blood smear Increasing splenomegaly Development of >1 of following constitutional symptoms >10% weight loss in 6 months Night sweats Unexplained fever Dita Gratzinger MD PhD [surgpathcriteria.stanford.edu]

• Plethora

  PV is also associated with a plethora of symptoms that are poorly controlled by conventional therapy. This article summarizes my approach to the management of PV in daily clinical practice. [ncbi.nlm.nih.gov]

  […] warm bath/shower venous thrombosis e.g. acute superior mesenteric venous thrombosis, dural venous sinus thrombosis, Budd-Chiari syndrome arterial thrombosis e.g. splenic infarction, ischemic stroke, myocardial infarction conjunctival injection facial plethora [radiopaedia.org]

  Physical examination reveals plethora and engorged retinal veins. The spleen is palpable in 75% of cases but is nearly always enlarged when imaged. [accessmedicine.mhmedical.com]

  /erythema -67%, Conjunctival plethora-59%, Engorged vessels in the optic fluid- 46%, Systolic BP>140 mm Hg- 72%, Diastolic BP>90 mm Hg- 32% CAUSES : unknown DIFFERENTIAL DIAGNOSIS Secondary polycythemias Hemoglobinopathy Spurious polycythemia LABORATORY [enotes.tripod.com]

  […] is not well described in the Brazilian population, being reported worldwide as close to 2 cases per 100 thousand inhabitants/year.1,2 The disease is described as polysymptomatic and its typical manifestations consist of headache, dizziness, weakness, plethora [htct.com.br]

• Easy Bruising

  Some patients with PV will not demonstrate any symptoms at all, but many will experience easy bruising or bleeding with little or no injury. Also, the blood may be thick and gummy, causing it to clot in tiny blood vessels. [uihc.org]

  Case 2 25 years old, male patient was referred to hematology clinic with complaints of weakness, headache, itching and easy bruising on areas open for trauma. Patient had no history of chronic diseases, drug using and smoking. [oatext.com]

  Individuals, who demonstrate signs and symptoms, have the following: Trouble breathing, feeling weak and tired Easy bruising and bleeding Severe, throbbing headache Skin appears red, or skin color changes due to lack of oxygen (blue) Visual problems, [dovemed.com]

  Prevent bleeding and bruising. PV or blood thinners used to manage it can increase your risk for heavy bleeding and easy bruising. Use an electric razor and soft toothbrush. Floss your teeth gently. Do not play contact sports, such as football. [drugs.com]

• Dyspnea

  Three patients experienced serious AEs (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9%) patients (4 PV, 3 ET). TRIAL REGISTRATION: ClinicalTrials.gov NCT01998828. Copyright © 2017 The Authors. [ncbi.nlm.nih.gov]

  Symptoms and Signs of Polycythemia Vera Polycythemia vera itself is often asymptomatic, but eventually the increased red cell volume and viscosity cause weakness, headache, light-headedness, visual disturbances, fatigue, and dyspnea. [msdmanuals.com]

  Predominant sex: Male > Female (slightly) SIGNS AND SYMPTOMS: Early stages may produce no symptoms Symptoms flushing, headache, dizziness, tinnitus, visual disturbances, pruritus, dyspnea, lassitude, or weakness. [enotes.tripod.com]

  Clinically there is dyspnea. relative polycythemia apparent polycythemia resulting from loss of plasma and the hemoconcentration that follows. Called also spurious polycythemia. polycythemia vera see primary polycythemia (above). [medical-dictionary.thefreedictionary.com]

  Symptoms and Signs Polycythemia vera itself is often asymptomatic, but eventually the increased red cell volume and viscosity cause weakness, headache, light-headedness, visual disturbances, fatigue, and dyspnea. [merck.com]

• Hepatomegaly

  Nonspecific neurological symptoms : dizziness, headache, visual disturbances, tinnitus Hypertension Splenomegaly : associated with early satiety and abdominal discomfort; less commonly hepatomegaly Peptic ulcer disease Symptoms of thrombotic and hemorrhagic [amboss.com]

  Less common symptoms associated with polycythemia vera include a tendency to bruise easily, frequent nosebleeds or bleeding from the gums, enlargement of the liver (hepatomegaly), and erythromelalgia, a condition characterized by a reddened or purplish [rarediseases.org]

  Hepatomegaly is common, and splenomegaly is present in 75% of cases. One-third of patients is hypertensive. Hypermetabolism can cause low-grade fevers and weight loss and suggests disease progression. Investigations: Raised Hb. Raised red cell mass. [askhematologist.com]

  […] per dL (180 g per L) in white men, > 16 g per dL (160 g per L) in blacks and women) Plethora Pruritus after bathing Splenomegaly Weight loss Weakness Sweating Less Common Bruising/epistaxis Budd-Chiari syndrome Erythromelalgia Gout Hemorrhagic events Hepatomegaly [aafp.org]

• Hepatosplenomegaly

  Myelofibrosis can develop in the bone marrow, leading to progressive hepatosplenomegaly. [unboundmedicine.com]

  Physical examination reveals multiple bruises on the bilateral upper and lower extremities and hepatosplenomegaly. Fundoscopic examination demonstrates enlarged retinal veins. Multiple laboratory tests are pending. [step1.medbullets.com]

  Transition of Polycythemia Vera to Chronic Neutrophilic Leukemia Abstract Chronic Neutrophilic Leukemia (CNL) is a rare myeloproliferative disorder characterized by a persistent increase of mature peripheral neutrophils, myeloid hyperplasia in bone marrow, hepatosplenomegaly [kjim.org]

  No lymphadenopathy or hepatosplenomegaly can be palpated. Other systems, including the cardiac, respiratory, and nervous systems, are normal. ERYTHROCYTOSIS AND POLYCYTHEMIA VERA 1. [mdedge.com]

  In some patients, however, the myelofibrosis is accompanied by significant extramedullary hematopoiesis, hepatosplenomegaly, and transfusion-dependent anemia. [theoncologyinstitute.com]

• Headache

  One visible symptom of polycythemia vera are headaches, according to this research from the National Institutes of Health. By reducing blood flow to the brain, painful headaches can become quite common. [activebeat.com]

  Headache, weakness, sweating, itching after a warm bath, and dizziness are all symptoms. How Is The Diagnosis Of Polycythemia Vera Made? Diagnosis may be made from a combination of a physical exam, certain blood tests, and a bone marrow biopsy. [illinoiscancercare.com]

  Symptoms include lack of energy (fatigue) or weakness, headaches, dizziness, shortness of breath, visual disturbances, nose bleeds, bleeding gums, heavy menstrual periods, and bruising. [hopkinsmedicine.org]

  […] in speech numbness, tingling, or weakness in arms or legs pain or swelling in arms or legs shortness of breath ruddy color in the face, hands, and feet chest pain sweating increased cough coughing up blood Cardiopulmonary problem symptoms dizziness headaches [uihc.org]

  Thus, the reported case behaved in an atypical manner: the patient presented only headache and splenomegaly of the classic symptoms, in addition to a rare manifestation of organic psychosis. [htct.com.br]

• Stroke

  PV increases the risk of abnormal blood clots, which could lead to a heart attack or stroke. This disease occurs most often in people who are 60 years old or older. [familydoctor.org]

  Polycythemia vera (PV) is a risk factor for systemic thromboses and ischemic stroke. This has been attributed to blood hyperviscosity, the result of increased blood cell production. [ncbi.nlm.nih.gov]

  That makes you less likely to get blood clots, which in turn makes heart attacks or strokes less likely. Most people with polycythemia vera take low-dose aspirin. Medicine to lower blood cells. [webmd.com]

  It can cause blood clots resulting in a heart attack, stroke, or pulmonary embolism. Liver and spleen enlargement are other possible complications. [hopkinsmedicine.org]

• Dizziness

  Headache, weakness, sweating, itching after a warm bath, and dizziness are all symptoms. How Is The Diagnosis Of Polycythemia Vera Made? Diagnosis may be made from a combination of a physical exam, certain blood tests, and a bone marrow biopsy. [illinoiscancercare.com]

  Symptoms include lack of energy (fatigue) or weakness, headaches, dizziness, shortness of breath, visual disturbances, nose bleeds, bleeding gums, heavy menstrual periods, and bruising. [hopkinsmedicine.org]

  […] of the spleen symptoms discomfort or bloating in the abdomen enlargement of the abdomen weight loss backache stomach pain blood in your stools or rectal bleeding Clotting symptoms redness or burning sensation in the fingers, hands, and feet fatigue dizziness [uihc.org]

  The presenting symptoms are frequently vague and consist of fatigue, headaches, dizziness, bleeding, pruritus, dyspepsia, and thrombosis. [medlink.com]

• Vertigo

  The vertigo nature was false or distorted sensations of swaying, rocking, bobbing, or bouncing of oneself (internal non-spinning vertigo). His vertigo was accompanied by severe headache and nausea, which was aggravated by moving his head. [e-rvs.org]

  Headaches Sweating and night sweats Ringing in the ears Blurred vision or blind spots Dizziness or vertigo Skin with red or purple hue Reddened face Unexpected weight loss Bleeding or clotting excessively Feeling full quickly on eating Abnormal discomfort [texasoncology.com]

  Clinical description Symptoms are often insidious at onset and may include headache, dizziness, vertigo, tinnitus, visual disturbances, and pruritus after bathing, a ruddy complexion that manifests in the face, palms, nailbeds, mucosa and conjunctiva. [orpha.net]

• Paresthesia

  Here we report a case of a 70-year-old man with prior stroke and PV who developed Guillain-Barré syndrome, an acute inflammatory demyelinating disorder of peripheral nerves causing ascending paresis, numbness, and paresthesia, who was treated safely with [ncbi.nlm.nih.gov]

  If thrombotic complications occur in central nervous system, patient will have seizures, paralysis and paresthesia like features. [medicaljoyworks.com]

  Many patients have neurologic symptoms such as headaches, dizziness or vertigo, visual problems, and paresthesias at the time of diagnosis. [medlink.com]

  Weight loss Weakness Sweating Less Common Bruising/epistaxis Budd-Chiari syndrome Erythromelalgia Gout Hemorrhagic events Hepatomegaly Ischemic digits Thrombotic events Transient neurologic complaints (headache, tinnitus, dizziness, blurred vision, paresthesias [aafp.org]

  This may be the initial presentation of PV, and is reported in up to 60% of PV patients under the age of 40], Dizziness - 43%, Diaphoresis - 33%, Visual disturbances - 31%, Weight loss - 29%, Paresthesias - 29%, Dyspnea - 26%, Joint symptoms - 26%, Epigastric [enotes.tripod.com]

• Abdominal Pain

  MYTH: The patient's first complaint is usually abdominal pain from an enlarged spleen and liver. [journals.lww.com]

  Case: 58-Year-Old Woman Diagnosed With Polycythemia Vera November 2018 A 58-year old woman presents to PCP complaining of abdominal pain, dizziness and headaches PE: BP 140/85; Splenomegaly ~6 cm below left costal margin PMH: No prior history of thrombosis [targetedonc.com]

  Headaches Blurry vision Red skin on the face, hands, and feet Fatigue High blood pressure Dizziness Abdominal pain Periods of cognitive confusion Gout (inflammation of the joints) Itchy skin Abnormal bleeding and bruising. [news-medical.net]

  As PV progresses, more serious problems can occur, including: bleeding gums bleeding in the digestive tract heavy bleeding from small cuts joint swelling bone pain liver enlargement spleen enlargement blood clots, or thrombosis abdominal pain and fullness [healthline.com]

  Browse recently published Learning/CME Learning/CME View all learning/CME CME Conservative Oxygen Therapy during Mechanical Ventilation in the ICU Case 8-2020: An 89-Year-Old Man with Recurrent Abdominal Pain and Bloody Stools Complications of Unsafe [nejm.org]

• Vomiting

  Epigastric pain/ burning sensation, incresed with meals, nausea, vomiting and regurgitation with or with out blood stained vomitus/ tary colour stools. These patients are at risk of developing peptic ulcers. [medicaljoyworks.com]

  Symptoms varied and included cerebral ischemic attacks, mental concentration disturbances followed by throbbing headaches, nausea, vomiting, syncope or even seizures. [ncbi.nlm.nih.gov]

  Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters. [jakafi.com]

  Other common side effects include fatigue, headache, nausea, vomiting, diarrhea, or fever that seldom cause discontinuation of the drug. [peertechz.com]

  […] aphasia) Sudden blurred, double or decreased vision Sudden dizziness, loss of balance or loss of coordination A sudden, severe headache or an unusual headache, which may or may not be accompanied by a stiff neck, facial pain, pain between your eyes, vomiting [checkorphan.org]

• Early Satiety

  Early satiety Patients can complain early satiety because splenomegaly causes limitation in gastric stretching by taking extra space from the abdomen. [medicaljoyworks.com]

  It’s fatigue, inactivity, abdominal discomfort, early satiety, fevers, night sweats, weight loss, itching, bone pain, trouble concentrating, and that’s about it. So I would advise proactively asking those questions. Transcript edited for clarity. [targetedonc.com]

  Nonspecific neurological symptoms : dizziness, headache, visual disturbances, tinnitus Hypertension Splenomegaly : associated with early satiety and abdominal discomfort; less commonly hepatomegaly Peptic ulcer disease Symptoms of thrombotic and hemorrhagic [amboss.com]

  The MPN-SAF TSS asks about worst fatigue, early satiety, abdominal discomfort, inactivity, problems with concentration, night sweats, pruritus, bone pain, fever, and weight loss. Scoring ranged from 0 (none) to 10 (worst imaginable). [ajmc.com]

  Weight loss may result from early satiety or from the increased myeloproliferative activity of the abnormal clone. [emedicine.medscape.com]

• Nausea

  Epigastric pain/ burning sensation, incresed with meals, nausea, vomiting and regurgitation with or with out blood stained vomitus/ tary colour stools. These patients are at risk of developing peptic ulcers. [medicaljoyworks.com]

  Symptoms varied and included cerebral ischemic attacks, mental concentration disturbances followed by throbbing headaches, nausea, vomiting, syncope or even seizures. [ncbi.nlm.nih.gov]

  autoimmunity, hyperlipidemia Psychiatric disease, cardiovascular disease Radioactive phosphorus ( 32 P) Radiopharmaceutical Anemia, thrombocytopenia, leukopenia, Leukemia may develop after treatment Diarrhea, fever, nausea, emesis — Busulfan (Myleran [aafp.org]

• Loss of Appetite

  Hepatic venous thrombosis will present with abdominal distension(ascites), features of liver insufficiency like nausea, vomiting, loss of appetite, yellowish discoloration of eyes, generalized swelling and gastrointestinal bleeding( either as haemoptysis [medicaljoyworks.com]

  An enlarged spleen may also cause pressure on the stomach causing a feeling of fullness, indigestion and a loss of appetite. In some cases the liver may also be enlarged.This is called hepatomegaly. [leukaemia.org.au]

  Other symptoms may include: extreme tiredness loss of appetite weight loss depression See a GP if you have pain and stiffness for more than a week. They'll try to find out what's causing it. [nhs.uk]

  […] of appetite Unintended weight loss Depression When to see a doctor See your doctor if you have aches, pains or stiffness that: Is new Disrupts your sleep Limits your ability to do your usual activities, such as getting dressed Causes The exact cause [mayoclinic.org]

• Bleeding Gums

  Symptoms include lack of energy (fatigue) or weakness, headaches, dizziness, shortness of breath, visual disturbances, nose bleeds, bleeding gums, heavy menstrual periods, and bruising. [hopkinsmedicine.org]

• Thrombosis

  Features include: hypertension unbearable pruritus, classically after taking a warm bath/shower venous thrombosis e.g. acute superior mesenteric venous thrombosis, dural venous sinus thrombosis, Budd-Chiari syndrome arterial thrombosis e.g. splenic infarction [radiopaedia.org]

  Strokes can be Ischemic (80%), typically resulting... read more, deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. [msdmanuals.com]

  Patients with a history of a prior thrombosis, including an intra-abdominal venous thrombosis, can safely undergo pregnancy by switching from warfarin to low molecular weight heparin with weight-based administration. [cancertherapyadvisor.com]

  […] to estimate the likelihood of recurrent thrombosis. [ncbi.nlm.nih.gov]

• Hypertension

  Abstract In a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years [ncbi.nlm.nih.gov]

  The major symptoms are related to hypertension or to vascular abnormalities caused by the increased red cell mass. The cause is unknown. With currently available treatment, the median survival exceeds 10 years. [icd9data.com]

  Patients with primary PV are sometimes hypertensive, while some patients with essential hypertension may have relative polyglobulia which resolves after blood pressure control. [elsevier.es]

  2018 - New Code 2019 Billable/Specific Code Applicable To Group 5 pulmonary hypertension Pulmonary hypertension with unclear multifactorial mechanisms Pulmonary hypertension due to hematologic disorders Pulmonary hypertension due to metabolic disorders [icd10data.com]

• Chest Pain

  If the spleen becomes too enlarged, it can cause discomfort after eating, difficulty breathing, and chest pain. Every year, there are five new cases of PV per 1,000,000 people. [uihc.org]

  Eg; In cardiac complications, patient will present with chest pain, difficulty in bresthing, dizziness, sweating and other features of myocardial infarction/ angina. [medicaljoyworks.com]

  Blood clots in the liver and spleen can cause sudden, intense pain. Slowed blood flow also prevents enough oxygen-rich blood from reaching your organs. This can lead to angina (chest pain or discomfort) and heart failure. [hoacny.com]

  (Angina is chest pain or discomfort.) Overview Red blood cells carry oxygen to all parts of your body. They also remove carbon dioxide (a waste product) from your body’s cells and carry it to the lungs to be exhaled. [oncologynurseadvisor.com]

  You may have any of the following: Chest pain or discomfort Fatigue, weakness, or weight loss without trying Shortness of breath, or trouble breathing when you lie down Pressure on the left side of your abdomen, abdominal pain, or diarrhea Bulging veins [drugs.com]

• Cyanosis

  ER-ih-THRE-me-ah) Erythrocytosis (eh-RITH-ro-si-TO-sis) megalosplenica (MEG-ah-lo-SPLE-ne-kah) Myelopathic (MY-e-lo-PATH-ik) polycythemia Myeloproliferative (MY-e-lo-pro-LIF-er-ah-tiv) disorder Osler disease Polycythemia rubra vera Polycythemia with chronic cyanosis [hoacny.com]

  Primary polycythemia; Polycythemia rubra vera; Myeloproliferative disorder; Erythremia; Splenomegalic polycythemia; Vaquez's disease; Osler's disease; Polycythemia with chronic cyanosis; Erythrocytosis megalosplenica; Cryptogenic polycythemia Polycythemia [mountsinai.org]

  Alternative Names Primary polycythemia; Polycythemia rubra vera; Myeloproliferative disorder; Erythremia; Splenomegalic polycythemia; Vaquez's disease; Osler's disease; Polycythemia with chronic cyanosis; Erythrocytosis megalosplenica; Cryptogenic polycythemia [ufhealth.org]

  This causes a blue coloration of the skin (cyanosis). [aoporphan.com]

  Primary polycythemia; Polycythemia rubra vera; Myeloproliferative disorder; Erythremia; Splenomegalic polycythemia; Vaquez's disease; Osler's disease; Polycythemia with chronic cyanosis; Erythrocytosis megalosplenica; Cryptogenic polycythemia Kremyanskaya [nlm.nih.gov]

• Blurred Vision

  MIAs were frequently preceded or followed by ocular ischemic events of blurred vision, scotomas, transient flashing of the eyes, and sudden transient partial blindness preceded or followed erythromelalgia in the toes or fingers. [ncbi.nlm.nih.gov]

  Polycythemia Vera Signs and symptoms Symptoms related to expanded blood volume and increased viscosity Headache, tinnitus, dizziness, blurred vision, TIAs, and fatigue Generalized pruritus (aquagenic) Engorged retinal veins Palpable spleen (75%) Thrombosis [slideshare.net]

  The most common symptoms of polycythemia vera are fatigue, dizziness, increased sweating, redness in the face, blurred vision, and itchy skin especially after a hot shower. [osmosis.org]

  Symptoms may include: Lack of energy (fatigue) or weakness Headache Dizziness Shortness of breath and trouble breathing while lying down Vision problems, such as double vision, blurred vision, and blind spots Inability to concentrate Night sweats Face [hopkinsmedicine.org]

  […] and symptoms of PV include: Headaches, dizziness, and weakness Shortness of breath and problems breathing while lying down Feelings of pressure or fullness on the left side of the abdomen due to an enlarged spleen (an organ in the abdomen) Double or blurred [hoacny.com]

• Conjunctival Injection

  injection facial plethora erythromelalgia gout Genetics JAK2 mutations (particularly the V617F mutation) can be found in more than 95% of people with polycythemia vera. [radiopaedia.org]

  On examination, there may be a plethoric complexion, conjunctival injection or palpable splenomegaly, in addition to physical signs as a result of vascular complications. The disease can progress to post-polycythaemic myelofibrosis. [hemonc.mhmedical.com]

  GI discomfort and peptic ulcer disease are common, likely from increased histamine release from basophils and increased viscosity in gastrointestinal blood supply.[13] Patients can display a plethora and flushing of the face and palms, conjunctival injection [statpearls.com]

• Visual Impairment

  impairment Possible complications The most common complications are a result of the high viscosity (resistance to flow) of the blood, which can lead to blood clots (thrombosis). [aoporphan.com]

  Presenting non-specific symptoms of polycythemia vera are related to hypoxia and include: Headache Dizziness Visual impairment Tinnitus Angina pectoris The signs and symptoms found in individuals diagnosed with polycythemia vera include: Elevated red [symptoma.com]

  Microvascular symptoms, such as hearing or visual impairments, paresthesia, or headache, are common. [haematologica.org]

• Tinnitus

  Some people with polycythemia vera have headache, dizziness, tinnitus (tinnitus), impaired vision, or itchy skin. Other complications of polycythemia vera include splenomegaly, stomach ulcers, gout, heart disease and leukemia. [ivami.com]

  Polycythemia Vera Signs and symptoms Symptoms related to expanded blood volume and increased viscosity Headache, tinnitus, dizziness, blurred vision, TIAs, and fatigue Generalized pruritus (aquagenic) Engorged retinal veins Palpable spleen (75%) Thrombosis [slideshare.net]

  […] upper abdomen (due to enlarged spleen) Headache Itchiness, especially after a warm bath Red skin coloring, especially of the face Shortness of breath Symptoms of blood clots in veins near the skin surface (phlebitis) Vision problems Ringing in the ears (tinnitus [mountsinai.org]

  Headache, dizziness, tinnitus, blurred vision, and fatigue are common complaints related to expanded blood volume and increased blood viscosity. [accessmedicine.mhmedical.com]

• Sudden Hearing Loss

  The patient presented with a main complaint of sudden-onset bilateral tinnitus with one-sided hearing loss. The patient was treated medically with hydroxyurea, aspirin, and phlebotomy. [oamjms.eu]

• Pruritus

  Abstract Aquagenic pruritus is one of the main clinical features of polycythemia vera. The aim of this study was to analyse the clinical characteristics of aquagenic pruritus. [ncbi.nlm.nih.gov]

  Christelle Le Gall-Ianotto and Laurent Misery, Pruritus in Hematological Diseases (Including Aquagenic Pruritus), Pruritus, 10.1007/978-3-319-33142-3_36, (271-281), (2016). [doi.org]

• Night Sweats

  The severity of individual symptoms, except those of pruritus and night sweats, was not affected by CHR or the number of blood counts that were controlled. [ajmc.com]

  Our group has been very engaged in trying to quantify the symptom burden in these patients, whether it’s fatigue, night sweats, itching vascular symptoms, etc. [onclive.com]

  Symptoms can include fatigue, abdominal discomfort, early satiety, itching, night sweats, fever, bone pain, unintentional weight loss, inactivity and problems with concentration. [healio.com]

  In 2009, 10 years after the diagnosis, while the patient was still being treated with hydroxyurea and phlebotomies, he noticed worsening of general conditions and fatigue, and the appearance of night sweats; he also reported that his spleen volume had [ncbi.nlm.nih.gov]

  sweats Unexplained fever Dita Gratzinger MD PhD Tracy I George MD Department of Pathology Stanford University School of Medicine Stanford CA 94305-5342 Original posting: 10/23/11 [surgpathcriteria.stanford.edu]

• Flushing

  Clinical features include facial flushing, pruritus, erythromelalgia, headaches, and dizziness. Severe complications such as thrombotic events (e.g., stroke, Budd-Chiari syndrome) may occur. [amboss.com]

  Symptoms of Polycythemia Vera Frequent headaches and a feeling of pressure in the head Dizziness and ringing in the ears (tinnitus) Fatigue Blurred or double vision Flushed or itching skin Night sweats Shortness of breath Itchy or flushed skin Frequent [healthcommunities.com]

  As the disease progresses, symptoms include: Shortness of breath Dizziness Itchy or flushed skin Fatigue Headaches A tingling or burning sensation in the hands and feet What causes polycythemia vera? PV begins in the bone marrow. [familydoctor.org]

  […] of energy (fatigue) or weakness Headache Dizziness Shortness of breath and trouble breathing while lying down Vision problems, such as double vision, blurred vision, and blind spots Inability to concentrate Night sweats Face and becomes red and warm (flushed [hopkinsmedicine.org]

• Erythema

  Erythema, burning, and pain in the extremities, a symptom complex known as erythromelalgia, is another complication of the thrombocytosis of PV. [theoncologyinstitute.com]

  […] age of 40], Dizziness - 43%, Diaphoresis - 33%, Visual disturbances - 31%, Weight loss - 29%, Paresthesias - 29%, Dyspnea - 26%, Joint symptoms - 26%, Epigastric discomfort - 24% Physical Findings Splenomegaly -70%; Hepatomegaly- 40%, Skin plethora/erythema [enotes.tripod.com]

  Other symptoms of PV include headaches, dizziness, ringing in the ears (tinnitus), and impaired vision.[2] The skin may also become itchy (pruritus) or reddened (erythema). [rarediseases.info.nih.gov]

  The symptoms are burning pain in the feet, hands, toes and fingers, sometimes associated with pallor, erythema, or cyanosis. Occasionally, it progresses to gangrene. [symptoma.com]

  Fewer than 5% of patients have erythromelalgia: This is erythema, warmth, pain and even sometimes infarction of the distal extremities. The hands and feet have a painful burning sensation. [patient.info]

• Chronic Urticaria

  Soter, Acute and chronic urticaria and angioedema, Journal of the American Academy of Dermatology, 25, 1, (146), (1991). JULIA A. NEWTON, A.K. SINGH, M.W. GREAVES and C.J.F. [doi.org]

• Bone Pain

  Treatments for Symptoms Aspirin can relieve bone pain and burning feelings in your hands or feet that you may have as a result of PV. Aspirin also thins your blood, so it reduces the risk of blood clots. [hoacny.com]

  Symptoms may include: Abnormal and heavy bleeding due to a cut or a nosebleed Intense and frequent bone pain and/or muscle pain Headaches, lightheadedness or gastrointestinal symptoms Vision problems Ringing in the ears Difficulty or labored breathing [cancer.uvahealth.com]

  It’s fatigue, inactivity, abdominal discomfort, early satiety, fevers, night sweats, weight loss, itching, bone pain, trouble concentrating, and that’s about it. So I would advise proactively asking those questions. Transcript edited for clarity. [targetedonc.com]

  pain Gout attacks Shortness of breath Weakness Bruising excessively Numbness or tingling in feet Prevention PV cannot be prevented. [texasoncology.com]

• Arthralgia

  Hypertension 0000822 Myelodysplasia 0002863 Myelofibrosis 0011974 Splenomegaly Increased spleen size 0001744 Tinnitus Ringing in ears Ringing in the ears [ more ] 0000360 Vertigo Dizzy spell 0002321 Weight loss 0001824 30%-79% of people have these symptoms Arthralgia [rarediseases.info.nih.gov]

• Joint Swelling

  As PV progresses, more serious problems can occur, including: bleeding gums bleeding in the digestive tract heavy bleeding from small cuts joint swelling bone pain liver enlargement spleen enlargement blood clots, or thrombosis abdominal pain and fullness [healthline.com]

  swelling You may also feel pressure or fullness below your ribs on your left side. [webmd.com]

  Common symptoms of polycythemia vera include: Dizziness Generalized fatigue Headaches Difficulty breathing Enlarged abdomen or abdominal fullness due to splenomegaly (large spleen) Itchy skin Painful joint swelling, especially in the large toe Prolonged [verywellhealth.com]

• Epistaxis

  Epistaxis is probably related to engorgement of mucosal blood vessels in combination with abnormal hemostasis. Sixty percent of patients are men, and the median age at presentation is 60 years. [accessmedicine.mhmedical.com]

  Thrombotic complications Venous thrombosis Arterial thrombosis Hemorrhagic complications Petechiae Epistaxis Bleeding gums References:[2][4][10][16] We list the most important complications. The selection is not exhaustive. [amboss.com]

  Bleeding complications occur in ~ 1% of patients with polycythemia vera and include epistaxis, gum bleeding, ecchymoses, and gastrointestinal bleeding. [symptoma.com]

  […] men, > 47 percent (0.47) in blacks and women Hemoglobin level > 18 g per dL (180 g per L) in white men, > 16 g per dL (160 g per L) in blacks and women) Plethora Pruritus after bathing Splenomegaly Weight loss Weakness Sweating Less Common Bruising/epistaxis [aafp.org]

  Digital ischemia, easy bruising, epistaxis, acid-peptic disease, or gastrointestinal hemorrhage may occur due to vascular stasis or thrombocytosis. [theoncologyinstitute.com]

The presence of the Janus kinase-2 (JAK2 V617F) mutation is diagnostic for polycythemia vera [4] [5] [12]. However, 2-3% of patients are negative for this genetic marker [12] [13]. The absence of the Janus kinase-2 mutation combined with a normal or increased serum erythropoietin level, excludes the diagnosis [9]. These patients have secondary erythrocytosis rather than polycythemia vera [5] [12].

Diagnostic criteria for polycythemia vera according to the World Health Organization guidelines require the presence of both major criteria and one minor criterion or the presence of the first major criterion together with two minor criteria [12] [14].

Major criteria [10] [12] [13]:

• Elevated red cell mass >25% or Hemoglobin > 18.5 g/dL (Hematocrit >60) in men and > 16.5 g/dL (Hematocrit >56) in women
• Presence of Janus kinase-2 mutation

Minor criteria [10] [12] [13]:

• Palpable splenomegaly
• Decreased serum erythropoietin level 
• Bone marrow biopsy showing erythroid, granulocytic, and megakaryocytic proliferation 
• Endogenous erythroid colony formation in vitro

Laboratory studies suggested for evaluation of polycythemia vera [2] [4] [12] [13]:

• Janus kinase-2 mutation analysis
• Direct measurement of the red blood cell mass is often not possible
• Complete blood count: Red blood cell counts with hematocrit and hemoglobin levels, Red blood cells are generally normochromic and normocytic, White blood cell count (>12,000/µL) primarily neutrophils with a left shift, Platelet count is elevated to 400,000-800,000/µL

• Serum erythropoietin level 
• Erythroid progenitor cell assay
• Leukocyte alkaline phosphatase (LAP) is elevated (>100 U/L)
• Routine coagulation tests are usually normal, 
• Vitamin B-12 levels elevated to > 900 /mL
• Oxygen saturation (SaO2) and carboxyhemoglobin (COHb) levels
• Iron studies

Imaging 

An enlarged spleen is often palpable and in such cases, imaging studies are not required [12] [13]. Ultrasonography or computed tomography scans may be able to detect splenic enlargement that was not evident on physical examination [12].

The diagnosis of Budd-Chiari syndrome is made using ultrasonography, computed tomography scan and magnetic resonance imaging [18].

Other tests

Bone marrow studies are not necessary to establish the diagnosis of polycythemia vera [2] [4]. They are important in identifying transformation to acute leukemia [4] [5]. Patients should be followed monthly until normalization of blood cell counts and splenomegaly, then every 2 months for complete blood count and blood smear evaluation [5].

• Erythrocytosis

  In patients with only an elevated hematocrit, polycythemia vera may be present, but secondary erythrocytosis Secondary Erythrocytosis Secondary erythrocytosis is erythrocytosis that develops secondary to disorders that cause tissue hypoxia, inappropriately [msdmanuals.com]

  Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. [ncbi.nlm.nih.gov]

  Beware of other conditions that can mimic polycythemia vera: Erythrocytosis Any cause of absolute erythrocytosis can mimic polycythemia. [cancertherapyadvisor.com]

  Increased production confined to the RBC line is termed erythrocytosis; isolated erythrocytosis may occur with polycythemia vera but is more commonly due to other causes (see secondary erythrocytosis ). [merck.com]

• Thrombocytosis

  For example, isolated thrombocytosis, whether associated with a JAK2 mutation or not, can be the presenting manifestation of essential thrombocytosis, primary myelofibrosis, or polycythemia vera, while both essential thrombocytosis and primary myelofibrosis [cancertherapyadvisor.com]

  Therapy for thrombocytosis in polycythemia vera Considerably less uniformity was noted among physicians regarding treatment of thrombocytosis. [doi.org]

  Hydroxyurea (62.8%) and anagrelide (35.4%) were the primary agents used to treat thrombocytosis. [ncbi.nlm.nih.gov]

  thrombocytosis or isolated leukocytosis, or any combination of these. [jhu.pure.elsevier.com]

• Neutrophilia

  Blood film examination showed neutrophilia (8.9 × 10⁹ /L) but immature myeloid cells and nucleated erythroblasts were absent. The spleen was 14 cm below the left costal margin, the liver was at 4 cm below the right costal margin. [ncbi.nlm.nih.gov]

  Splenomegaly ++ ++ +++ ± ± Absent Clinical/Other B symptoms Hypertension, thrombosis, pruritus, ↓EPO B symptoms, bleeding, gout Thrombosis, hemorrhage Anemia Anemia EPO = erythropoietin, * rare p230 BCR-ABL1 isoform can present with thrombocytosis and /or neutrophilia [surgpathcriteria.stanford.edu]

  The increased WBC is the result of neutrophilia; the absolute count of basophils is also often increased. The blood film appears 'packed' as a result of the increased viscosity of the blood (Figure 6.1). [hemonc.mhmedical.com]

  The neutrophilia presented by the patient was considered as a possible sign of infection, initiating an infectious screening of the patient. [htct.com.br]

  Some patients may show at diagnosis palpable splenomegaly, thrombocytosis (platelets above 400 x 109/L), neutrophilia (neutrophils above 10 x 109/L). Endogenous erythroid colonies usually grow in vitro and serum erythropoietin levels are low. [atlasgeneticsoncology.org]

• Hyperglobulinemia

  Chronic polycythemia caused by a genetic mutation affecting hematopoietic stem cells, characterized by increased blood volume, bone marrow hyperplasia, redness of the skin, and splenic enlargement. polycythemia vera polycythemia vera Hyperglobulinemia [medical-dictionary.thefreedictionary.com]

• Vitamin B12 Increased

  Polycythemia Vera Laboratory findings Elevated Hct – often >60% Increased WBCs and platelets Serum EPO levels are low Decreased iron stores (Ferritin) Increased Vitamin B12 Increased uric acid Presence of the JAK2 mutation Hypercellular bone marrow 5. [slideshare.net]

• Plasma Volume Increased

  Review Topic QID: 109194 1 Increased plasma volume, increased RBC mass, decreased EPO, normal SaO2 2 Normal plasma volume, increased RBC mass, increased EPO, normal SaO2 3 Decreased plasma volume, normal RBC mass, normal EPO, normal SaO2 4 Normal plasma [step1.medbullets.com]

• Hypercellular Bone Marrow

  Polycythemia Vera Laboratory findings Elevated Hct – often >60% Increased WBCs and platelets Serum EPO levels are low Decreased iron stores (Ferritin) Increased Vitamin B12 Increased uric acid Presence of the JAK2 mutation Hypercellular bone marrow 5. [slideshare.net]

  Definition Dysregulated expansion of the red blood cell mass Diagnostic Criteria Prodromal, pre-polycythemic diagnosis is difficult to make Borderline to mild erythrocytosis Bone marrow biopsy showing panmyelosis with decreased erythropoietin may be helpful [surgpathcriteria.stanford.edu]

  bone marrow with trilineage growth, and (3) presence of a JAK2 mutation; minor criteria: hypercellular bone marrow with trilineage growth, low serum erythropoietin levels, and endogenous erythroid colony formation). [hindawi.com]

  Hypercellular bone marrow Panmyelosis Mild increase in reticulin fibers Leukoerythroblastosis Fibrosis and erythroid islands Core biopsy with dense fibrosis Core biopsy with extensive fibrosis   Bone marrow core biopsy with leukemic transformation (AML [pathologyoutlines.com]

• Bone Marrow with Hyperplasia

  Bone marrow aspiration (red cell hyperplasia, absent iron stores) and biopsy (fibrosis during spent phase of the disease) Drugs that may alter lab results: Diuretics may cause a spurious polycythemia. [enotes.tripod.com]

• Bone Marrow with Erythroid Hyperplasia

  Marrow Biopsy: Erythroid hyperplasia Cytogenetics: JAK-V617F mutation [targetedonc.com]

The goal of treatment for polycythemia vera is to control myeloproliferation [10] [15] and decrease the risk of arterial and venous thrombotic events, which occur in approximately 20% of patients [2] [9]. The optimum management plan is unclear. Significant differences exist among physicians about the appropriate management of the disease [2]. Consultation with and management by a hematologist is recommended [5].

General guidelines for the management of polycythemia vera include [2] [5] [9] [15]:

• Maintain a hematocrit of 44% or less is the target
• Minimize the risk of transformation to acute leukemia and myelofibrosis
• Manage complications such as thrombosis and hemorrhage

Medical management:

• Phlebotomy alone is the first choice
• A combination of phlebotomy and hydroxyurea
• Hydroxyurea alone, (interferon, 32P or busulfan are used infrequently)
• Low-dose aspirin
• Treatment of thrombocytosis recommended for platelet counts above 400,000

All patients with polycythemia vera require phlebotomy to keep their hematocrit levels below 44% [5] [15]. This treatment removes excess red blood cells and lowers blood viscosity [10]. Patients can be phlebotomized once or twice a week [5] [10]. Elderly patients with cardiovascular or cerebral vascular conditions should have volume replaced with saline solution after each procedure to avoid postural hypotension [10]. Chemotherapy and phlebotomy can decrease the risk for thrombotic events [11].

Patients with this disorder should routinely take low-dose aspirin, 81 mg daily [5]. Low-dose aspirin suppresses thromboxane biosynthesis resulting from increased platelets and essential thrombocythemia [5] [11]. Treatment with aspirin may also reduce the risk of myocardial infarction, stroke, or death from cardiovascular causes, pulmonary embolism, or major venous thrombosis [10] [11]. The incidence of major bleeding episodes was not significantly increased with aspirin [11].

Patient at high risk for thrombosis should have drug therapy to decrease blood cell production. Hydroxyurea at a starting dose of 500 mg twice daily is the most commonly used agent. It is an effective agent for myelosuppression [5]. It reduced the risk of thrombosis when compared with phlebotomy [5]. It should be the drug of choice for patients older than 40 years [6]. However, there are concerns that it may increase the long-term risks of leukemic transformation [6]. 

Interferon-alpha can be used as an alternative [9] [10]. Studies have shown that treatment with this drug was not as effective when compared with hydroxyurea. However, interferon alfa 2b had a lower transformation rate and no severe hematological adverse effects [8].

Busulfan is also an option for patients older than 65 years of age who do not respond to hydroxyurea [10].

Ruxolitinib (Jakafi), a Janus-associated kinase inhibitor, is the first US Food and Drug Administration drug approved specifically for polycythemia vera [1]. It is approved for use in patients with polycythemia vera who cannot tolerate or had an inadequate response to hydroxyurea [1]. Patients who received ruxolitinib had a significant reduction in splenomegaly [12] [13].

Once the patient's red blood cell values are reduced periodic phlebotomies or a myelosuppressive agent should be continued to maintain disease control [5] [10].

Splenectomy should be only considered in patients with painful splenomegaly or splenic infarction [10] [11]. Treatment of Budd-Chiari syndrome includes portal or mesenteric-systemic shunting, catheter-directed thrombolysis, and liver transplantation [18].

Untreated polycythemia has a very poor prognosis. The median survival in untreated patients is 1.5-3 years. Treated this may be extended to at least 10-20 years [1]. Thrombosis is the leading cause of death [10]. Thrombotic complications including stroke and other arterial thromboses occur in ~1% of patients. The risk of thrombosis depends on age of the patient and their past history of thrombosis. Patients older than 60 years or with a previous history of thrombosis are considered at high risk [1] [10].

Bleeding complications occur in ~ 1% of patients with polycythemia vera and include epistaxis, gum bleeding, ecchymoses, and gastrointestinal bleeding [8].

The long-term risks of polycythemia vera include leukemic and fibrotic transformation occurring in 5-10% of patients [8] [9] [15]. Studies have suggested an increased risk for all neoplasms with the use of chemotherapic agents in polycythemia vera.

Vaquez is credited with the initial description of polycythemia vera in 1892. The clinical features were first described by Osler in 1903 [2]. In 1967, the Polycythemia Vera Study Group identified criteria for diagnosis and treatment of the disease [2] [5].

The etiology of all the myeloproliferative disorders is unknown [3]. The cause of the symptoms of polycythemia vera is an uncontrolled blood cell proliferation [4] [12] [13]. The abnormal cell production is a mutation in the Janus kinase-2 gene [13]. The cause if this mutation is unknown. Virtually all patients with polycythemia vera have the mutation. The discovery of the Janus kinase-2 gene mutation has improved the diagnosis of polycythemia vera [13].

The mean age of incidence of polycythemia vera is 50-70 years [8], but it can occur in all age groups, although rarely in childhood [7] [14]. Familial cases are very rare usually in elderly family members [7].

The severity of polycythemia vera and the rate of progression vary from patient to patient [8]. All myeloproliferative disorders, including polycythemia vera, are pre-leukemic as they can transform to acute leukemia over time. The rate of leukemic transformation in polycythemia vera is 5-10% of patients [8] [15].

Polycythemia vera is relatively rare, affecting in 0.6-1.6/million population [10]. The disorder can occur at any age, but it has a median age at onset of 60 years [10]. Studies have shown that this condition concerns all ethnic groups [1]. Polycythemia vera occurs almost equally in both sexes [12], though a few studies have found that slightly more males than females are affected [2].

Myeloproliferative disorders like polycythemia vera are hematopoietic stem cell malignancies [3] [8]. Abnormal stem cells present in the bone marrow of patients with polycythemia vera suppress normal stem cell maturation [12].

These abnormal blood stem cells respond aberrantly to growth factors [4]. A mutation on the Janus kinase-2 gene (JAK2) is the most likely gene involved in polycythemia vera [4] [6] [12]. It is thought that the defect alters the signal from growth enzymes to the stem cells [12]. Polycythemia vera stem cells are hypersensitive to erythropoietin and hematopoietic growth factors [8]. This mutation occurs in most (> 80%) polycythemia vera patients [6]. The mutation leads to tyrosine phosphorylation activation that causes cytokine hypersensitivity that induces erythrocytosis [6] [8].

Serum levels of erythropoietin are normal or subnormal in polycythemia vera patients, therefore the hyperproliferation is not stimulated extrinsically and the disease is classified as a primary polycythemia [8].

In polycythemia vera excessive red blood cells are produced in the bone marrow [1]. Patients may also experience an increase in white blood cells and platelets [1]. These blood cells show no cytogenetic abnormality, all blood cells produced are normal [8]. The overabundance of blood cells causes splenomegaly, bleeding problems, and thrombosis [1] [14]. Studies have shown that hematocrits above 44 are associated with an increased number of thromboembolic events [2].

Thrombotic events in polycythemia vera are the result of the increased viscosity of the blood due to the excessive numbers of blood cells. Increased thromboxane synthesis occurs as well due to thromboxane-dependent platelet activation [11]. This is a major cause of the increased risk of thrombosis. Low-dose aspirin suppresses the production of thromboxane by platelets in patients with high platelet counts and [11].

A paradoxical bleeding or hemorrhagic tendency occurs with high platelet counts that resembles acquired Von Willebrand disease in patients with polycythemia vera[16].

As in all the myleoproliferative disorders, polycythemia vera may progress to blood malignancies such as acute leukemia and myleofibrosis [9]. Transformation rates are estimated to be 10-20% [9] [10]. Leukemic transformation of polycythemia vera can be influenced by pharmacotherapy such as alkylating agents [10]. Acute leukemia is thought to be a part of the natural course of polycythemia vera [11].

Budd–Chiari syndrome, obstruction and occlusion of the suprahepatic veins, is a rare life-threatening complication in polycythemia vera [7]. It is the result of thrombosis within the vasculature of the liver[18].

Differential diagnoses for polycythemia vera include [7] [9]:

• Chronic myeloid leukemia (CML)
• Agnogenic myeloid metaplasia (AMM)
• Fibrotic myelofibrosis
• Conditions causing systemic hypoxia
• Conditions stimulating erythropoietin secretion
• Infections or leukemoid reactions
• Thrombocytosis from bleeding
• Iron deficiency
• Essential thrombocytosis

A cause for the development of the Janus kinase-2 genetic mutation is unknown, therefore there is no way to prevent its occurrence.

Phlebotomy, myelosuppressive drugs, and anticoagulants can prevent thrombosis, stroke, liver and renal damage, and other cardiovascular events [10] [11]. Studies have shown that low dose aspirin (81 mg/d) is effective for preventing thrombosis without causing bleeding [11].

Polycythemia vera is a chronic myeloproliferative stem cell disorder [1] [2]. It is one of several acquired myeloproliferative diseases that are considered malignant bone marrow disorders [1] [3] [4]. Polycythemia vera and the other myeloproliferative diseases are relatively uncommon [5].

The primary characteristic of polycythemia vera is an elevated absolute red blood cell count due to uncontrolled red blood cell production [2]. Panmyelosis may also be seen as increased white blood cell and platelet production [1] [2]. Other characteristic features of polycythemia vera are splenomegaly, a predisposition to venous/arterial thrombosis, and bleeding [6]. It can eventually progress to myelofibrosis, and acute leukemia [2].

Polycythemia vera arises from acquired mutations in a hematopoietic stem cell [7] [8]. The mechanisms accounting for the development of these mutations are poorly understood [8]. The genetic mutations of polycythemia vera usually occurs sporadically, but occasional familial cases have been reported [7]. The median age at diagnosis of polycythemia vera is 60 years of age [11]. It is a progressive disease and approximately 5% of patients progress to acute leukemia [9] [10].

The rise in red blood cell load in polycythemia vera results in hyperviscosity of the blood and subsequent circulatory disturbances. The primary cause of death is acute cardiovascular or cerebrovascular events [11].

What is polycythemia vera ?

Polycythemia vera is a chronic disease of blood cell producing stem cells of the bone marrow. The overproduction of red blood cells, primarily, white blood cells and platelets occur because of a genetic mutation of these stem cells. The median age at diagnosis is 60 years of age. Although disease itself is not fatal, death will occur within 1 ½ to 3 years from cardiovascular complications of blood clot formation.

What are the symptoms?

Polycythemia vera is often asymptomatic at first. It may initially present with non-specific symptoms of decreased oxygen supply such as: headache, dizziness, vertigo, and angina. Other individuals will not be diagnosed until they experience a major blood clotting event.

The clinical signs of the disorder are:

• Elevated red blood cell count; hematocrit over 60
• Elevated white blood cell and platelet count
• Enlarged spleen
• Tendency for abnormal clotting

What causes polycythemia vera?

The cause is a mutation of the Janus Kinase-2 gene that is responsible for the regulation of blood cell production. Because of this mutation blood cell production is excessive. The extreme number of circulating blood cells causes the blood to be more viscous increasing the risk of blood clot formation.

Who gets polycythemia vera?

Polycythemia vera can occur at any age, however it is rare in individuals younger than 40 years of age. Mean age at onset is 60 years.

How is it diagnosed?

The definitive diagnosis of polycythemia vera is made when the Janus Kinase-2 gene mutation is detected. Routine blood tests will show an excessive increase in red blood cells, white blood cells, and platelets.

How is polycythemia vera treated?

Polycythemia vera is treated primarily with periodic phlebotomy, blood-letting, to remove excessive blood cells and reduce blood viscosity. Myelosupressive medications, such as Hydroxyurea, reduce blood cell production. All patients are also given low-dose aspirin to prevent clotting.

What are the complications?

The complications of polycythemia vera are due to abnormal clotting and include:

• Stroke
• Pulmonary emboli
• Myocardial infarct
• Circulatory compromise in the extremities
• Obstructive liver disease
• Obstructive renal damage

How can it be prevented?

Since a cause of the Janus kinase-2 genetic mutation is unknown, there is no way to prevent polycythemia vera. Phlebotomy, myelosuppressive drugs, and anticoagulants can prevent the complications of the disease and extend life expectancy.

1. Berlin NI. Diagnosis and classification of the polycythemias. Semin Hematol. 1975;12(4):339-51.
2. 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;99(4):1144-9.
3. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-8.
4. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in Understanding and Management of Myeloproliferative Neoplasms. Cancer J Clin. 2009;59:171-191.
5. Passamonti F. How to manage polycythemia vera. Leukemia. 2012; 26(5):870-4.
6. 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;52(3):134-9.
7. Cario H, Pahl HL, Schwarz K, et al. Familial polycythemia vera with Budd–Chiari syndrome in childhood. British Journal of Haematology, 2003, 123, 346–352.
8. Pahl HL. Towards a molecular understanding of polycythemia rubra vera. Eur. J. Biochem. 2000;267, 3395-3401.
9. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk-stratificati on. American Journal of Hematology. 2012; 87:285 293.
10. McMullin MF, Bareford D, Campbell P, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/ erythrocytosis. British Journal of Haematology. 2005;, 130, 174–195.
11. Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114-24.
12. 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;106(10):3374-6.
13. Guglielmelli P, Barosi G, Pieri L, Antonioli E, Bosi A, Vannucchi AM. 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;94(1):144-6.
14. Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol. 1986;23(2):132-43.
15. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. New Eng J Med. 2013;368(1):22-33.