POLYCYTHEMIADr. Sookun Rajeev K

(MD)

Dept of General Medicine

Anna Medical College

POLYCYTHEMIA– Definition?

Polycythemia is a blood disorder inwhich the body produces too manyblood cells as a result of a problemwith the bone marrow or an increasedproduction of the hormoneerythropoietin(EPO).

POLYCYTHEMIA– Definition?• Often patients with polycythemia are detected

through an incidental finding of elevatedhemoglobin or hematocrit levels.

• Concern that the hemoglobin level may beabnormally high is usually triggered at 170 g/L(17 g/dL) for men and 150 g/L (15 g/dL)forwomen.

• Hematocrit levels >50% in men or >45% inwomen may be abnormal.

CLASSIFICATIONPOLYCYTHEMIA

RELATIVE ABSOLUTE

SECONDARY

APPROPRIATE INAPPROPRIATE

PRIMARY

Relative Polycythemia

Low Volume States

• Dehydration

• Burns

• Prolonged vomitings

• Diarrhea

• Excessive diuretics

• Stress or Gaisbock syndrome

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

Polycythemia Vera

• Polycythemia vera is a slow-growingtype of blood cancer in which your bonemarrow makes too many red blood cells.

• Polycythemia vera may also result inproduction of too many of the othertypes of blood cells — white blood cellsand platelets.

• The JAK2 gene provides instructions for making aprotein that promotes the growth and division(proliferation) of cells.

• This protein is part of a signaling pathway calledthe JAK/STAT pathway, which transmits chemicalsignals from outside the cell to the cell's nucleus.

• The JAK2 protein is especially important forcontrolling the production of blood cells fromhematopoietic stem cells.

• These stem cells are located within the bonemarrow and have the potential to develop into

red blood cells, white blood cells, and platelets.

EtiologyMutation causes the disorder• The problem with blood cell production associated with

polycythemia vera is caused by a change, or mutation, to DNAin a single cell in your bone marrow. In polycythemia vera,researchers have found this mutation to be a change in aprotein switch that tells the cells to grow. Specifically it's amutation in the protein JAK2 (the JAK2 V617F mutation). Morethan 90 percent of patients with polycythemia vera, and abouthalf of patients with other myeloproliferative disorders, havethis mutation. Doctors and researchers don't understand thefull role of this mutation and its implications for treating thedisease.

• The DNA mutation that causes polycythemia vera occurs afterconception — meaning that your mother and father don't haveit — so it's acquired, rather than inherited from a parent.Researchers and doctors don't know what causes the mutation.

Risk FactorsSome factors may increase your risk of developingpolycythemia vera :

• Age - Polycythemia vera is more common inadults and older than 60. It's rare in peopleyounger than 20

• Sex - Polycythemia vera affects men more oftenthan it does women.

• Family history - In some cases, polycythemia veraappears to run in families, indicating that geneticfactors other than JAK2 may contribute to thedisease.

Signs & SymptomsIn its early stages, polycythemia vera usually doesn'tcause any signs or symptoms. As the disease progresses,the following Symptoms may be experienced:

1. Headache

2. Dizziness

3. Itchiness, especially following a warm bath orshower

4. Redness of your skin and plethoric facialappearance

5. Shortness of breath

6. Breathing difficulty when pt is lying supine

Signs & Symptoms

7. Numbness, tingling, burning or weakness in the hands, feet, arms or legs

8. Chest pain

9. A feeling of fullness or bloating in your left upper abdomen due to an enlarged spleen

10.Fatigue

• Bleeding complications, seen in approximately 1% ofpatients with PV, include epistaxis, gum bleeding,ecchymoses, and gastrointestinal (GI) bleeding.Thrombotic complications (1%) include venousthrombosis or thromboembolism and an increasedprevalence of stroke and other arterial thromboses.

• Abdominal pain due to Peptic Ulcer Disease may bepresent because PV is associated with increasedhistamine levels and gastric acidity or possible Budd-Chiari Syndrome (hepatic portal vein thrombosis).

• Pruritus results from increased histamine levelsreleased from increased basophils and mast cells andcan be exacerbated by a warm bath or shower. Thisoccurs in up to 40% of patients with PV.

Hematological TestsFBC1. An increase in the number of red blood cells

and, in some cases, an increase in platelets or white blood cells.

2. Elevated hematocrit measurement, the percentage of red blood cells that make up total blood volume.

3. Elevated levels of hemoglobin, the iron-rich protein in red blood cells that carries oxygen.

Hematological TestsABG1. 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.

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.

Bone marrow aspiration or biopsy

Polycythemia vera is a chroniccondition that can't be cured.Treatment focuses on reducing theamount of blood cells in order tocontrol signs and symptoms of thedisease and decrease the risk ofcomplications.

1. Phlebotomy

This is usually the first treatment option formost people with polycythemia vera.Phlebotomy involves drawing a certainamount of blood from one of the veins. Thisreduces the number of blood cells anddecreases the blood volume, making it easierfor the blood to function properly.How often the patient needs phlebotomydepends on the severity of your condition.

2. Medication to decrease blood cells.

Phlebotomy alone may not be enough to control the signs,symptoms and complications of polycythemia vera in somepeople. If this is the case, then medications such ashydroxyurea or anagrelide to suppress the bone marrow'sability to produce blood cells.

Radioactive phosphorus (32p) also can be used to reducethe number of red blood cells.

Interferon-alpha may be used to stimulate the immunesystem to fight the overproduction of red blood cells.

3.Low-dose aspirin.

Aspirin to reduce your risk ofblood clots. Low-dose aspirinmay also help reduce burningpain in feet or hands.

4. Therapy to reduce itching.

Antihistamines or H-2-receptor blockers, or ultraviolet light treatment to relieve discomfort.

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.