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.
