Polycythemia by Dr. Sookun Rajeev Kumar

Polycythemia

1. POLYCYTHEMIA Dr. Sookun Rajeev K (MD) Dept of General Medicine Anna Medical College

2. POLYCYTHEMIA– Definition? Polycythemia  is a blood disorder in which the body produces too many blood cells as a result of a problem with the bone marrow or an increased production of the hormone erythropoietin(EPO).

3. POLYCYTHEMIA– Definition? Often patients with polycythemia are detected through an incidental finding of elevated hemoglobin or hematocrit levels. Concern that the hemoglobin level may be abnormally high is usually triggered at 170 g/L (17 g/ dL ) for men and 150 g/L (15 g/ dL )for women. Hematocrit levels >50% in men or >45% in women may be abnormal.

4. CLASSIFICATION

5. Relative Polycythemia Low Volume States Dehydration Burns Prolonged vomitings Diarrhea Excessive diuretics Stress or Gaisbock syndrome

6. Absolute Polycythemia Primary Polycythemia also known as Polycythemia Vera is caused by a problem with the bone marrow resulting in an overproduction of cells Secondary Polycythemia is caused by an increased production of erythropoietin resulting in an overproduction of red blood cells

7. Polycythemia Vera Polycythemia vera is a slow-growing type of blood cancer in which your bone marrow makes too many red blood cells.  Polycythemia vera  may also result in production of too many of the other types of blood cells — white blood cells and platelets.

8. The  JAK2  gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. These stem cells are located within the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets .

9. Etiology Mutation causes the disorder The problem with blood cell production associated with polycythemia vera is caused by a change, or mutation, to DNA in a single cell in your bone marrow. In polycythemia vera , researchers have found this mutation to be a change in a protein switch that tells the cells to grow. Specifically it's a mutation in the protein JAK2 (the JAK2 V617F mutation). More than 90 percent of patients with polycythemia vera , and about half of patients with other myeloproliferative disorders, have this mutation. Doctors and researchers don't understand the full role of this mutation and its implications for treating the disease. The DNA mutation that causes polycythemia vera occurs after conception — meaning that your mother and father don't have it — so it's acquired, rather than inherited from a parent. Researchers and doctors don't know what causes the mutation.

10. Risk Factors Some factors may increase your risk of developing polycythemia vera : Age - Polycythemia vera is more common in adults and older than 60. It's rare in people younger than 20 Sex - Polycythemia vera affects men more often than it does women. Family history - In some cases, polycythemia vera appears to run in families, indicating that genetic factors other than JAK2 may contribute to the disease.

11. CLINICAL FEATURES

12. Signs & Symptoms In its early stages, polycythemia vera usually doesn't cause any signs or symptoms. As the disease progresses, the following Symptoms may be experienced: Headache Dizziness Itchiness, especially following a warm bath or shower Redness of your skin and plethoric  facial appearance Shortness of breath Breathing difficulty when pt is lying supine

13. Signs & Symptoms Numbness, tingling, burning or weakness in the hands, feet, arms or legs Chest pain A feeling of fullness or bloating in your left upper abdomen due to an enlarged spleen Fatigue

14. Bleeding complications , seen in approximately 1% of patients with PV, include epistaxis , gum bleeding, ecchymoses , and gastrointestinal (GI) bleeding. Thrombotic complications (1%) include venous thrombosis or thromboembolism and an increased prevalence of stroke and other arterial thromboses. Abdominal pain due to Peptic Ulcer Disease may be present because PV is associated with increased histamine levels and gastric acidity or possible Budd- Chiari Syndrome (hepatic portal vein thrombosis). Pruritus results from increased histamine levels released from increased basophils and mast cells and can be exacerbated by a warm bath or shower. This occurs in up to 40% of patients with PV.

15. DIAGNOSIS

16. Hematological Tests FBC An increase in the number of red blood cells and, in some cases, an increase in platelets or white blood cells. Elevated hematocrit measurement , the percentage of red blood cells that make up total blood volume. Elevated levels of hemoglobin , the iron-rich protein in red blood cells that carries oxygen.

17. Hematological Tests ABG Lower than normal levels of oxygen  in the blood. Erythropoietin Very low levels of erythropoietin (EPO) , a hormone that stimulates bone marrow to produce new red blood cells, because the excess red blood cells turn off the production of EPO by the kidneys.

18. Bone marrow aspiration or biopsy Examination of bone marrow shows that it's producing higher than normal amounts of blood cells, it may be a sign of polycythemia vera . If the individuals have polycythemia vera , analysis of their bone marrow or blood also may show the DNA change (JAK2 V617F mutation) that's associated with the disease.

19. Bone marrow aspiration or biopsy

20. TREATMENT

21. Polycythemia vera is a chronic condition that can't be cured. Treatment focuses on reducing the amount of blood cells in order to control signs and symptoms of the disease and decrease the risk of complications.

22. 1. Phlebotomy This is usually the first treatment option for most people with polycythemia vera . Phlebotomy involves drawing a certain amount of blood from one of the veins. This reduces the number of blood cells and decreases the blood volume, making it easier for the blood to function properly. How often the patient needs phlebotomy depends on the severity of your condition.

23. 2. Medication to decrease blood cells.  Phlebotomy alone may not be enough to control the signs, symptoms and complications of polycythemia vera in some people. If this is the case, then medications such as hydroxyurea or anagrelide to suppress the bone marrow's ability to produce blood cells. Radioactive phosphorus (32p) also can be used to reduce the number of red blood cells. Interferon-alpha may be used to stimulate the immune system to fight the overproduction of red blood cells.

24. 3.Low-dose aspirin. Aspirin to reduce your risk of blood clots. Low-dose aspirin may also help reduce burning pain in feet or hands.

25. 4. Therapy to reduce itching.   A ntihistamines or H-2-receptor blockers, or ultraviolet light treatment to relieve discomfort.

26. Second line therapy for PV Ruxolitinib ( Jakafi ), a JAK1/JAK2 inhibitor, was approved by the FDA in December 2014 for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea .