Polycythemia Vera (PV)

Polycythemia Vera (PV) is a bone marrow disease that results primarily in the over production of red blood cells (RBCs). In many patients the numbers of white blood cells and blood platelets are also elevated. The increase in RBCs and platelets can create serious and potentially fatal complications for the patient. In addition, PV can develop into chronic leukemia or other related bone marrow malignancies.

The mean age of diagnosis of PV is 60 years with the male to female ratio being about 1.4:1.

The "cause" of PV is an acquired mutation of the DNA in the bone marrow. An abnormal "stem cell" shifts into overdrive and out produces the millions of other similar cells in the marrow. The mutant cell line comes to dominate blood cell production. The RBCs being produced by the mutant cells are nearly normal but they are made in excessive numbers. What are the symptoms of PV?

Many patients with PV are without symptoms (called asymptomatic) and are first identified on a routine blood examination.

If a patient has symptoms from PV, they are often related to the abnormally high number of blood cells. Symptoms usually come on gradually, and may include:

Headache Weakness Fatigue Light-headedness or dizziness Itching, especially after a hot shower or bath Visual impairments Shortness of breath or trouble breathing A red color to the skin, especially in the face Abnormal bleeding Bone pain A blood clot in a vein, also called deep venous thrombosis

About one fifth of patients with PV present with a clotting event such as a deep vein thrombosis, heart attack or a stroke.

How is PV diagnosed?

PV is diagnosed based on three primary criteria:

1. Elevated red blood cell (RBC) count 2. Normal oxygen blood gas reading (i.e. >92% oxygen in arterial blood with room air) 3. Enlargement of the spleen (called splenomega)

In addition to the primary criteria above, the following "minor criteria" can also suggest PV:

1. Elevated platelet count 2. Elevated white blood cell (WBC) count 3. Elevated alkaline phosphatase level

The standard test for determining the concentration of red cells, white cells and platelets in the blood is called a "complete blood cell count" or CBC. See this link for an excellent review of the basics of the CBC http://www.heartcenteronline.com/myheartdr/common/ articles.cfm?ARTID=205

Normal RBC count for women is 4.6 million cells Normal RBC count for men is 5.2 million cells

In PV, the RBCs will be elevated. In addition, the actual percentage of RBCs in the blood will also be elevated. The test that measures the "level or percentage of RBC cells in the blood" is called the hematocrit.

Normal hematocrit for women average 42% Normal hematocrit for men averages 47%

Lastly there is the hemoglobin. Hemoglobin is the compound in RBCs that carries oxygen.

Normal hemoglobin in women is 14 grams/100 milliliters. Normal hemoglobin in men is 16 grams/100 milliliters.

At the time of diagnosis with PV, the hematocrit and hemoglobin concentration are increased in the same proportion as the RBCs.

In addition to an increase in the RBCs, hematocrit and hemoglobin concentration, platelets are generally elevated.

How is PV treated?

Treatment of PV is based on the "rate of progression" of the disease (i.e. how quickly the RBCs and platelets are rising), the patient’s age and the presence of other medical problems. The primary goal of treatment is reduce the number of RBCs to near normal levels. If the platelet count is high, it will also require treatment.

The following are treatments used in PV:

Phlebotomy This is the removal of blood similar to a blood donation. It is generally the first step in the treatment of PV. A volume of blood is withdrawn at regular intervals with the goal of decreasing the number of RBCs for a period of weeks to months. This may be the sole form of treatment for many PV patients for years.

When phlebotomy is the sole treatment for PV, the average rate of survival is extended more than 12 years.

Drug Therapy Aspirin is used to reduce blood clots by making platelets less "sticky."

Anagredlide (brand name Agrylin ) is used to lower the platelet count (see this link for an overview of anagredlide http://www.nlm.nih.gov/medlineplus/druginfo/ anagrelidesystemic203493.html).

Hydroxyurea (brand name Hydrea ) is used with or without phlebotomy to suppress bone marrow production of RBCs and platelets (see this link for an overview of hydroxurea http:/ /www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682004.html).

Chlorambucil (brand name Leukeran ) is used with or without phlebotomy to suppress bone marrow production of RBCs and platelets (see this link for an overview of chlorambucilhttp://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682899.html ).

Interferon-alpha is used with patients who cannot tolerate hydroxurea or for whom the medication stops working.

Radiotherapy Radiotherapy is the form of radioactive phosphorus can be given in a liquid form to older patients. One or two treatments may decrease RBC and platelet production reducing the need for phlebotomy or drugs for long periods.

Adding bone marrow suppressing medications (i.e. Hydrea or Leukeran) or radiotherapy to phlebotomy appears to reduce survival time as well increases the risk of patients developing acute leukemia.

Underwriting Comment Clients with PV are insurable but under specific conditions. It is important to remember that symptomatic patients who go untreated have life expectancy of 18 months.

Clients with PV who are insurable must be able to verify clinical stability. This includes a white blood count of less than 14,000 and a platelet count less than 500,000. In addition they must be in the first ten (10) years of the disease. Clients with PV longer than ten years duration may be insurable, but are considered on an individual basis.

Use the following questions to screen clients with PV:

1. When was the client diagnosed with PV?

Treatment clearly extends the life expectancy of clients with PV but the duration of the disease is a crucial piece of underwriting information.

2. What type of treatment (s) is the client undergoing to manage their PV?

Is the client being treated with phlebotomy alone or are medications being used?

3. Are the client’s RBCs, WBCs and platelets close to normal range?

Most clients with PV either know or can find out this information.

4. Has the client has any complication from their PV?

This includes a history of deep vein blood clots, visual problems, and lung and heart problems.

5. Does the client currently smoke?

PV is enough of an increased risk factor for clotting complications without adding in the complication of smoking. Clients with PV who continue to smoke are considered a poor risk for individual coverage.

6. Does the client have any other medical problems?

7. Does the client take any other medications?