MPN patients may hear the term “allele burden” associated with their diagnosis and treatment. An allele is a variant or different form of a specific gene. In MPN, allele burden refers to the proportion of cells that harbor the JAK2 mutation. Although it is not routinely used in clinical practice, some interesting observations have occurred in regard to allele burden. For example, in MF patients who underwent stem cell transplant, achieving a negative allele burden was associated with a decreased risk of recurrence.2 Additionally, allele burden may be helpful in determining the risk of having a thrombotic event (blood clot).3
At this time, the data is still considered controversial, and more study is necessary. Therefore, monitoring allele burden is not currently a standard of care but is sometimes performed at academic medical centers or as part of a clinical trial.
Polycythemia Vera (PV)
What is PV?
Patients with PV have too many red blood cells. In some cases, they may also have too many white blood cells and platelets. Having too many red blood cells can cause the blood to thicken, which makes it more difficult to flow normally through arteries and veins.
Like other forms of MPN, the exact cause of PV is unknown, although evidence suggests that JAKs are involved. In fact, about 95% of all PV patients have a JAK mutation. As discussed, JAK proteins send signals that affect the production of blood cells in the bone marrow. If the JAKs send too many signals, the bone marrow makes too many blood cells, causing PV.
PV affects each person differently. Some patients with PV have no symptoms. In others, PV can be more severe. For example, some patients develop an enlarged spleen. Because the spleen helps your body fight infection and filters unwanted material, such as old or damaged blood cells, the increased number of blood cells caused by PV makes your spleen work harder than normal. This extra work may cause the spleen to get bigger, and lead to abdominal discomfort and feeling full quickly when eating.
Sometimes PV is discovered after a blood clot occurs and your healthcare providers are looking for the cause. Much like ET, the most worrisome complication is blood clots in major vessels, such as in the heart, lungs or brain.
In a very small percentage of people, PV leads to other blood diseases, such as myelofibrosis (MF), a disease in which scar tissue develops in the bone marrow, or leukemia.
PV is most commonly diagnosed in men over the age of 60, but can occur in both men and women of any age.
In addition to elevated red and white blood cells and platelets, general symptoms of PV may include (but are not limited to):
• Elevated LDH (an enzyme found in cells)
• High blood pressure
• Enlarged spleen or liver (along with abdominal discomfort or the sensation of feeling full quickly)
• General skin itchiness (pruritis), which may be worse when taking a shower
• Redness of hands and feet (erythromelagia)
• Blood clots
• Hemorrhage
• Facial redness
• Gout or arthritis
• Fatigue
• Psychosocial symptoms (depression, anxiety, etc.)
• Sleep disturbance
• Dizziness
• Headache
How is PV diagnosed?
PV can be diagnosed by:
• A blood test which looks at blood “counts,” including the number of red blood cells, white blood cells and platelets.
• Molecular tests (done on the blood or with a bone marrow biopsy to determine gene mutations)
• Bone marrow biopsy to evaluate if there are changes in bone marrow that confirms the diagnosis or rules out other diseases, especially the possibility of fibrosis (scarring) in the bone marrow, which may change treatment decisions or prognosis.
• A blood test to look at erythropoietin level, or “EPO” level. Erythropoietin is a protein that stimulates red blood cell production in the bone marrow. EPO levels should be normal or low in PV. If the level is high, then other causes, such as lung disease, smoking, sleep apnea or high altitude, should be considered.
World Health Organization (WHO) Criteria for Polycythemia Vera:
The diagnostic criteria for PV were updated in 2016, with two major changes: the hemoglobin (a part of the blood that transports oxygen) threshold was lowered to 16.5 g/dl, and a bone marrow biopsy is now considered a major component for diagnosis.
A diagnosis of PV requires meeting all three major criteria or two major criteria and the minor criterion.
| Major Criteria | Minor Criterion |
| Hemoglobin > 16.5 g/dl in women or hematocrit >49% in men; >48% in women or increased red cell mass (RCM) | Low level or normal blood erythropoietin (EPO) level |
| Bone marrow biopsy showing changes consistent with PV | |
| Presence of JAK2 V617F or JAK2 exon 12 mutation |
How is PV treated?
PV is a chronic and sometimes progressive disease, which means it may get worse over time. However, PV can be managed by keeping blood counts under control. Like ET, understanding your risk for events such as heart attack and stroke is important when determining treatment. High risk factors include being 60 years of age or older and having a history of blood clots, heart attack or stroke.
For patients who are considered “low risk,” treatment often consists of removing blood (phlebotomy). Your healthcare team will monitor your blood counts, and if hematocrit levels (the volume of red blood cells) get too high (>45%), a phlebotomy is recommended. The frequency of this procedure will depend on your disease and your physician’s treatment plan. In addition, a daily aspirin is often recommended, depending on your medical history, and should be discussed with your doctor.
Other therapies may be considered, such as hydroxyurea, interferon, ruxolitinib, piprobroman, and related drugs, if you are considered high risk for a thrombotic event (blood clot).
What is the magic of the 45% or less
hematocrit goal?
A study was performed (Cyto PV study published by Marchioli et al) which revealed that patients who had phlebotomy (blood removal) with a hematocrit goal higher than 45% had a 4x increase in cardiovascular death or thrombosis (blood clot). Be sure you are hitting the proper goal, and discuss with your physician if your hematocrit level is higher than 45%.
Making Your Phlebotomy Easier
Removing blood can be stressful for some people. To make things easier, be sure to drink plenty of water the day before your phlebotomy. Staying hydrated is important because it helps decrease dizziness by keeping the blood volume as normal as possible before removing it. Hydration also helps the veins “plump,” which makes it easier to find a vein that can easily be punctured, Additionally, try to limit caffeine on the day prior to a blood draw, as it acts as a mild diuretic and increases the amount of urine you produce,
