In polycythemia vera, there are increased blood cell levels due to overproduction by
the bone marrow, which is a soft tissue found within the bones.
Normally, about 45% of the total blood volume is made up of erythrocytes, or red blood cells,
and their main function is to carry oxygen to tissues and bring carbon dioxide to the
lungs so it can be expired.
This value is called the hematocrit.
In polycythemia vera there’s an increase in red blood cell production.
It typically begins with a mutation in a single hematopoietic stem cell, which gives rise
to red blood cells, white blood cells, and platelets.
In 90 percent of the affected individuals there is a mutation of the Janus Kinase 2
or JAK2 gene.
Normally, the kidneys produce erythropoietin which is a hormone that binds to receptors
on the hematopoietic stem cells and activates JAK2 gene.
When that happens, it causes the cell to divide and thus produce more blood cells.
However, when there’s a mutation, it keeps JAK2 gene activated, and these cells are able
to divide even in the absence of erythropoietin.
The mutated cells proliferate, and rapidly become the predominant hematopoietic cells
in the bone marrow.
In time these cells start to die out and that’s when scar tissue forms.
At that point, the bone marrow can no longer produce blood cells, leading to anemia or
low red blood cell levels, thrombocytopenia or low platelet levels, and leukopenia or
low white blood cell levels.
This is known as the spent phase.
And once the disease is in the spent phase, it’s really a different disease altogether
- at that point it’s myelofibrosis.
The most common symptoms of polycythemia vera are fatigue, dizziness, increased sweating,
redness in the face, blurred vision, and itchy skin especially after a hot shower.
Itchiness develops due to the increased number of basophils and mast cells which contain
histamine that causes itching when released.
Splenomegaly or spleen enlargement is also common because the excess red blood cells
buildup in the spleen, which usually helps with removing excess cells.
High turnover of red blood cells can cause build up of uric acid which leads to the inflammation
of joints or gout and kidney stones.
Individuals with polycythemia vera are more prone to blood clots and their complications
like stroke, heart attack, deep vein thrombosis and Budd-Chiari syndrome, which is when liver
veins are blocked by a blood clot.
Sometimes the disorder can be found during a routine blood test.
Common findings include increased hemoglobin or hematocrit levels, as well as an increased
white blood cell and platelet count.
Most individuals have decreased erythropoietin, but some individuals have normal or even elevated
erythropoietin levels.
Bone marrow tissue examination or biopsy can be done to look for signs of fibrosis, and
genetic testing can be done to look for the JAK2 gene mutation.
Most individuals require phlebotomy, which is when the blood is drawn through a vein
and removed every few months.
This blood is not donated for other individuals, but can be used for the autologous donation,
so the donor can use it in the future if needed.
Myelosuppressive medication, like hydroxyurea; as well as the JAK2 inhibitor, ruxolitinib;
can be used to lower red blood cell formation.
Ruxolitinib is also particularly helpful with relieving symptoms like itching - other medications
that can also help relieve symptoms include antihistamines, hydroxyzine, and aspirin.
Aspirin is also used to help prevent clotting.
In the spent phase, individuals may need blood transfusions at regular intervals.
All right, as a quick recap polycythemia vera is an overproduction of blood cells often
caused by a JAK2 mutation within hematopoietic cells in the bone marrow.
It can lead to an elevated hemoglobin and hematocrit and predispose an individual to
developing blood clots.
Treatment includes: removing blood at regular intervals, medication to lower blood cell
formation, and prevention of blood clots.
Patients may progress to myelofibrosis, which represents a “spent phase,” of the bone
marrow where individuals may need blood transfusions or more aggressive therapy.