POLYCYTHEMIA VERA – Etiology, Risk Factors, Pathophysiology, Clinical Manifestations, Diagnostic Evaluation and Management
Polycythemia vera is a chronic myoproliferated disorder that involves all bone marrow elements, resulting in an increase in RBC mass or presence of increased in number of RBC and hemoglobin. Polycythemia is an abnormal increased in concentration of hemoglobin in the blood, either through reduction of plasma volume or increase in red cell numbers.
- Polycythemia vera is a bone marrow disease that leads to an abnormal increase in the number of blood cells (mainly RBCs), although the number of white blood cells and platelets are also increased.
- It is associated with gene mutations. The cause of this mutation is unknown
- Polycythemia is also associates with problems of the bone marrow
- Other causes may includes smoking, minning, or environmental factors
Some of the chronic risk factors:
- Chronic hypoxia
- Reduction of plasma volume
- Long-term cigarette smoking
- Familial and genetic predisposition
- Living in high altitudes
- Long-term exposure to carbon monoxide (tunnel worker, Car garbage attendants, residents of highly polluted cities)
Polycythemia is due to excessive production of a single line of clonal stem cells present in the bone marrow. These cells interfere with or stimulate normal stem cells growth and maturation. Unregulated neoplastic proliferation is thought to be the etiology. The origin of the abnormal clonal cells is currently unknown however these cells have increased sensitivity to growth factors for maturations, indicating the presence of detect in the single pathway common to different growth factors. Clonal and cytogenic studies are currently under way in an attempt to determine the molecular basis of PV.
Chromosomal mutation in single pluripotent stem cells —- RBCs, WBCs and platelets lead to increased sensitivity to growth —- overproductions of all three blood cells lines most predominantly RBCs, increased cell mass —- increased blood volume and blood viscosity —- leads to engorgement of blood vessels and possible thrombosis —- further leads to the congestion of organs —- the patients may have coagulopathies predispose to clotting, splenomegaly and hepatomegaly
TYPES OF POLYCYTHEMIA
Polycythemia can be divided into two categories-primary and secondary. Polycythemia can result from internal problems with the production of red cells. This is termed primary polycythemia. If polycythemia is caused due to another underlying medical problem it is referred to as secondary polycythemia
Polycythemia Vera is known as primary polycythemia. Its cause is unknown. Polycythemia Vera is a disorder of the proliferative bone marrow in which the myeloid cells stem cells seems to have escaped normal control mechanism. It is caused by much production of white blood cells, red blood cells and platelets. The bone marrow is hyper cellular and the WBCs, RBCs and platelet count in the peripheral blood are elevated the skin takes a ruddy appearance from the buildup cells. PV is found in patients over age 50 years
Secondary polycythemia is caused by excessive production of erythropoietin disease. Secondary polycythemia generally occurs as a response to other factors or underlying conditions that promote red blood cells production. Secondary polycythemia is usually due to increased erythropoietin production either in response to chronic hypoxia this may be caused in response to a reduced amount of oxygen, which acts as hypoxic stimulus, as in cigarette smoking, COPD or cyanotic heart failure, obstructive sleep apnea, poor blood flow to the kidney, living in high altitudes and smoking. Secondary polycythemia is a compensatory mechanism rather than an actual disorder
Relative polycythemia describes condition in which red cell volume is high due to increased blood concentration of red cells as a result dehydration. In these situation (vomiting, diarrhea, excessive sweating) the number of red blood cells counts may seem elevated
This is a condition that may be seen in hardworking, anxious, middle-aged men due to blow plasma volume, although the red blood cells volume may be normal. Other names for this condition are pseudopolycythemia, stress erythrocytosis, or Gaisbock’s disease
Conditions which may result in a physiologically appropriate polycythemia include:
- Altitude related: this physiologic polycythemia is a normal adaptation to living at high altitudes. Many athletes train at high altitude to take advantage of this effect – a legal form of blood doping. Some individuals believe athletes with primary polycythemia may have a competitive advantage due to greater stamina. However, this has yet to be proven due to the multifaceted complications associated with this condition
- Hypoxic disease: associated – for example in cyanotic heart disease where blood oxygen levels are reduced significantly. May also occur as a result of hypoxic lung disease such as COPD and as a result of chronic obstructive sleep apnea
- Latrogenic: secondary polycythemia can be induced directly by phlebotomy, to withdraw some blood, concentrate the erythrocytes, and return them into the body.
- Genetic: heritable causes of secondary polycythemia also exist and are associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb Chesapeake, which has a greater inherent affinity for oxygen than normal adult hemoglobin. This reduces oxygen delivery to the kidneys, causing increased erythropoiten production and a resultant polycythemia. Hemoglobin kempsey also produces a similar clinical picture. These conditions are relatively uncommon.
Conditions where the secondary polycythemia is not as a result of physiologic adaptation and occurs irrespective of body needs include:
- Neoplasms: renal cell carcinoma or liver tumors, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing’s syndrome
- People whose testosterone levels are high because of the use of anabolic steroids, including athletes who abuse steroids, or people on testosterone replacement for hypogonadism, as well as people who take erythropoietin may develop secondary polycythemia
Many people have no symptoms when they are first diagnosed with polycythemia vera. This disease is often discovered during a blood routine blood test and physical examination. If symptoms develop, they tend to do so over time.
- Reddish, purple skin and mucosa, pruritus (especially after bathing)
- Breathing difficulty when lying down
- Excessive bledding (hemorrhage)
- Splenomegaly, hepatomegaly
- Epigastric discomfort, abdominal discomfort
- Painful fingers and toes paresthesia
- Headache, fullness in head, dizziness, visual abnormalities, alter mutation from disturbed cerebral circulation
- Weakness, fatigue, night sweats, bleeding tendency
- High blood pressure
Some of these symptoms are due to increased blood thickness and clotting
- The splenomegaly, hepatomegaly: The enlargements of the spleen are also common and occur in around 75% cases. Symptoms include feeling of fullness in the upper left-side of the abdomen. 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 is also enlarged called as hepatomegaly
- Painful inflammation of the toe or foot: this can results from build up for uric acid, a byproduct of the increased production and breakdown of blood cells. Some individuals may develop erytheromelagia, a rarely condition that primarily affects the feet and, less commonly the hands. It is characterized by intense, burning pain of affected extremities, and increased skin temperature that maybe episodic or almost continuous in nature.
- Hemorrhage: this phenomenon caused by either vessel capture from over distension or inadequate platelet function may results in ecchymosis, epistaxis, or GI bleeding. Hemorrhage can be acute and catastrophic.
The following laboratory manifestations are seen in a patient with polycythemia vera.
- Elevated Hb and RBC count with microcytosis
- Low to normal EPO level (secondary polycythemia will have a high level)
- Elevated WBC count with basophila
- Elevated platelets (thrombocytosis) and platelet dysfunction
- Elevated leukocyte alkaline phosphatase
- Elevated histamine levels
- Bone marrow in examination in polycythemia vera shows hypercellularity of RBCs, WBCs and platelets
- Splenomegaly is found in 90% of patient with primary polycythemia but does not accompany secondary polycythemia.
Routine blood work including:
- Clotting profile, and metabolic panel
- Chest X-ray, electrocardiogram (ECG), echocardiogram, hemoglobin analysis, carbon monoxide measurement
- Evidence of long standing low body oxygen level (chronic hypoxia) in an important clue in patient with polycythemia
- Bone marrow examination (bone marrow aspiration or biopsy)
- Full blood count (CBC): people with polycythemia vera have a high red cell count, hemoglobin level and hematocrit due to the excessive production of red cells. The hematocrit is the percentage of the whole blood that is made up of red cells. A raised white cell count (especially a raised neutrophil count) and a raised platelet count are also common findings
- JAK2 mutation testing: JAK2 mutations (particularly the V617F mutation) can be found in more than 95% of people with polycythemia vera. This test can be performed on a blood sample and will help to confirm the diagnosis of a myeloproliferative neoplasm. It does not help distinguish polycythemia vera from essential thrombocythemia or primary myelofibrosis.
- Bone marrow examination: in polycythemia vera, the bone marrow is often very active with abnormally high numbers of normal cells. Iron stores maybe depleted since iron is being used to make more and more red cells
Other possible blood tests
- Serum vitamin B12 levels
- Uric acid levels
- Erythropoietin levels
- Coagulation studies
- Blood oxygen levels
- Chest X-ray – to rule out lung disease
- Abdominal ultrasound and/or CT scan – to rule out kidney disease and measure spleen or liver size
- Phlebotomy: venesection (or phlebotomy) is a procedure in which a controlled amount of blood is removed from bloodstream. This procedure is commonly used when people are first diagnosed with polycythemia vera because it can help to rapidly reduce a high red cell count. In a process similar to a blood donation, 450 to 500 ml of blood is removed, usually from a large vein in the arm. This is usually done in the outpatient’s department of the hospital. It takes about 30 minutes to complete.
- Marrow Hyperplasia (Myelosuppressive Drugs): myelosuppressive (bone marrow suppressing) drugs or chemotherapy are commonly used to reduce blood cell production in the bone marrow. These drugs are commonly used for people with and extremely high platelet count, complications due to blood clotting or bleeding, or symptoms of an enlarged spleen. They are also used for some people who are unable to tolerate venesection or whose disease.
- The most commonly used myelosuppressive agent is a chemotherapy drug called hydroxyurea. It is particularly useful in controlling a high platelet count and therefore reducing the risk of thrombosis. As hydroxyurea is a chemotherapy drug, it is known to affect fertility and should be avoided during pregnancy, for it can cause harm or may be fatal to the fetus.
- Interferon: interferon is a substance produced naturally by the body’s immune system. It plays an important role in fighting disease. In polycythemia vera, interferon is sometimes prescribed for younger patients to help control the production of blood cells. Interferon is usually given three times a week as an injection under the skin (subcutaneous injection) using a very small needle. A weekly injection is also being given.
- Aspirin: many people are prescribed small daily doses of aspirin, which have been shown to significantly reduce the risk of thrombosis in people with polycythemia vera.
- Radioactive phosphorus: radioactive phosphorus (32P) is a radioisotope which may be used for long-lasting control of blood counts in older people. One or two doses of 32P are usually given by injection into a vein in the hand or arm, in the nuclear medicine department of the hospital. This substance is taken up and concentrated in bone marrow where it suppresses the overactive bone marrow and helps to control blood counts.
The patient who suffers from the polycythemia vera the family history and medical history and social history should be taken.
- A comprehensive medical history, physical examination, family history, and social and occupational history is very important.
- History include questions about smoking history, living at high altitudes for extended periods, breathing difficulties, sleep disturbances, or chronic cough
- A complete examination including the assessment of body habitus (stature), vital signs, oxygen saturation, heart and lungs exam, and evaluating for an enlarged spleen are essential in the evaluation of people with polycythemia
- Assess for the ruddy cyanosis, reddened face with engorged retinal vein, tinnitus, weakness, fatigue and dizziness
- Assess for the signs of parasthesia, numbness, tingling, burning or weakness in hands, feet’s or legs
- Assess for the hypertension, nose bleeding
- Assess for any enlargement of liver and spleen
- The primary polycythemia is not preventable. However, because secondary polycythemia is generated by the source of hypoxia, maintaining adequate oxygenation may prevent problems. Therefore, controlling chronic pulmonary disease, stopping smoking and avoiding altitudes maybe important
- The nurse have a responsibilities to assist with or perform phlebotomy if acute exacerbation of polycythemia
- Fluid intake and fluid output should be evaluated during hydration therapy to avoid fluid overload and under hydration
- If the myelosuppressive agents are used the nurses must administer the drugs as ordered, observe the patient, and teach the patient about medication side effects
- Assessment of the patient’s nutritional status in collaboration with the dietician may be necessary to of set the inadequate food intake that can useful from GI symptoms of fullness, pain and dyspepsia
- Activities should be instituted to decreased thrombus formation. The relative immobility normally imposed by hospitalization puts the patient at risk for thrombus formation. Active and passive exercises and ambulation when possible should be initiated.