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◉ What is Polycythemia Vera?
Polycythemia vera is a rare blood condition in which the bone marrow excessively produces red blood cells. These excess red blood cells increase the viscosity of the blood, and as it thickens, it slows down, increasing the risk for blood clots and other major problems.
Polycythemia is a general term used to describe an increase in cellular elements of the blood leading to an increase in both hemoglobin concentration and hematocrit (red blood cell mass).
It is considered as a type of leukemia, and it progresses over many years. If it is not managed and treated properly, it can be life threatening. Otherwise, patients can live a fairly long, happy life.
◉ Causes of Polycythemia Vera
Polycythemia vera is a myeloproliferative neoplastic disorder that originates essentially from a mutation in a gene called JAK2. The JAK2 gene gives out instructions that manage cell division within the bone marrow’s stem cells.
When diseased, regulation of red cell replication in the bone marrow is affected, leading to an overproduction of red blood cells.
It is the only myeloproliferative neoplastic disease in which erythrocytosis occurs, as other blood cancers cause anemia. Although it involves a genetic mutation, it is rarely inherited by offspring.
The latest studies show that the pathophysiology may also involve an increase in the sensitivity of the receptors that respond to growth factors on abnormal hematopoietic stem cells.
◉ Symptoms and signs
Polycythemia vera is mostly asymptomatic, but eventually, the increased volume and viscosity of red blood cells (RBCs) lead to symptoms such as fatigue and dyspnea. The symptoms of polycythemia vera develop slowly over many years.
1- Non-specific symptoms that can occur in other many disorders:
- Headache.
- Fatigue.
- Weakness.
- Dizziness.
- Tinnitus.
2- Vision changes
Refers to alterations in eyesight that may occur due to the increased viscosity of blood in Polycythemia vera, affecting blood flow to the eyes.
3- Insomnia
Difficulty in sleeping, which can be attributed to various factors such as discomfort or restless legs, often seen in patients with Polycythemia vera.
4- Claudication
Pain or cramping in the legs, typically during physical activity, caused by reduced blood flow to the muscles due to increased blood thickness.
5- Pruritus
Itching sensation of the skin. Some patients experience itching, especially during or after a hot shower, known as Aquagenic pruritus. This condition is linked to mast cell and basophil degranulation, leading to a surge in histamine.
6- Erythromelalgia
Burning pain sensation in the hands and feet associated with redness or pallor, likely due to altered blood circulation.
7- Abnormal bleeding
May manifest as nosebleeds (epistaxis), gastrointestinal bleeding, and gum bleeding due to disturbances in the clotting mechanism.
8- Thrombotic events
Occurrence of blood clots, including deep vein thrombosis (DVT), pulmonary embolism, Budd-Chiari syndrome, splanchnic vein thrombosis, and arterial and venous thrombosis.
9- Splenomegaly
Enlargement of the spleen, as it works to clear a higher number of blood cells in Polycythemia vera.
10- Early satiety and bloating
Feeling full quickly after eating and experiencing abdominal bloating, often a result of an enlarged spleen.
11- Peptic ulcer
Development of ulcers in the stomach or upper part of the small intestine, possibly due to increased blood volume and related complications.
12- Gout and kidney stones
Result from the high turnover of red blood cells, leading to elevated levels of uric acid, which can contribute to the formation of gout and kidney stones.
13- Plethora and facial redness
Excessive redness of the skin and face, possibly due to increased blood volume.
14- Conjunctival injection
Redness of the conjunctiva (the clear layer covering the white part of the eye), often associated with increased blood flow.
◉ Diagnosis
The diagnosis of polycythemia vera relies on obtaining a detailed medical and family history from the patient, along with the clinical presentation featuring characteristic findings in blood tests.
1- Complete blood count (CBC)
- Hemoglobin level (Hb): >16.5g/dl in men or >16g/dl in women. Hemoglobin levels may appear normal if there is concurrent iron deficiency anemia.
- Hematocrit levels: Above 49% in males and above 48% in females. However, hematocrit levels may not always be elevated, as they can be normal due to plasma expansion.
- Increased platelet count: This strongly suggests primary polycythemia.
- Elevated leukocyte count: 10,000-20,000/microliter. Eosinophilia and basophilia may be observed.
2- Serum erythropoietin (EPO) levels
- Low EPO levels: this indicates primary polycythemia.
- High EPO level indicates secondary polycythemia
3- Testing for JAK2V617F (exon 14) and JAK2 exon 12 mutations
If the result is negative, testing for CALR and LNK mutations should be conducted.
4- Bone marrow biopsy
Shows hypercellularity and panmyelosis, large clumped megakaryocytes, and may indicate an increase in reticulin fibers. However, there are no specific bone marrow findings that are pathognomonic for polycythemia vera.
5- Other tests
- Serum ferritin
- Vitamin B12
- Folate levels.
- Renal function tests.
◉ Treatment
The treatment of polycythemia vera must be individualized based on the patient's age, sex, medical status, clinical manifestations, and laboratory findings. The goal of treatment is to reduce red blood cell levels and prevent complications associated with the disorder.
1- Phlebotomy
This is the main line of treatment. Patients undergo weekly sessions during which approximately 500ml of blood is removed. This process is done weekly until the target hematocrit level falls below 45%.
2- Hydroxyurea
This is considered the second line of treatment with indications for use including difficult venous access, excessive phlebotomy requirements, non-possible phlebotomy, and severe thrombocytosis.
3- Ruxolitinib
This is a JAK2 inhibitor used if the patient is intolerant or unresponsive to hydroxyurea. The standard dose for polycythemia vera is 10mg twice a day, with a reduction in dose if the hemoglobin level drops below 12mg/dl.
4- Low-dose Aspirin
The dose may be increased if there is ineffective control of microvascular symptoms after achieving the target hematocrit. The recommended dose of aspirin is 40-100mg daily.
5- Hypouricemic agents
Drugs such as allopurinol and febuxostat may be used to treat hyperuricemia.
6- Pruritus treatment
Symptomatic relief can be achieved by using antihistamines and selective serotonin reuptake inhibitors (SSRIs).
◉ Conclusion
Polycythemia vera is a rare form of blood cancer characterized by the excessive production of red blood cells in the bone marrow due to a genetic mutation in the JAK2 gene. This condition impacts various bodily functions and organs, including the liver and spleen. The predominant symptoms are primarily linked to impaired oxygen delivery and blood hyperviscosity, with the mainstay of management being phlebotomy, supplemented by other modalities.