Polycythemia vera (PV) is a chronic blood cancer originating in the bone marrow, defined by the excessive production of red blood cells. This increases blood volume and thickness. A significant number of individuals with PV also have a high platelet count, a condition called thrombocytosis, which is a feature of the disease. The development of PV stems from a disorder in the body’s hematopoietic stem cells. The link between the overproduction of red blood cells and platelets is a direct consequence of a specific genetic alteration.
The Pathophysiological Link
Polycythemia vera originates from a mutation acquired in a single hematopoietic stem cell. The specific genetic flaw is most often found in the Janus kinase 2 (JAK2) gene, with a mutation known as V617F identified in more than 95% of people with PV. The JAK2 gene provides instructions for a protein involved in the JAK-STAT signaling pathway, which controls blood cell production.
The V617F mutation causes this pathway to be constantly active, even without normal signals from hormones. This leads to hematopoietic stem cells dividing and producing new blood cells without regulation. This uncontrolled proliferation is not selective. While the overproduction of red blood cells (erythrocytosis) is the most prominent feature of PV, the mutated stem cell also creates an excess of megakaryocytes. Megakaryocytes are the large bone marrow cells that produce platelets, so the same JAK2 mutation drives both high red blood cell counts and thrombocytosis.
Clinical Manifestations and Associated Risks
The combination of too many red blood cells and platelets causes a distinct set of symptoms and health risks. Some signs are directly related to the high platelet count, such as erythromelalgia, a condition of intense burning pain and redness in the hands and feet. Another common symptom is pruritus, a severe itching often triggered by warm water.
The most serious complication from PV with thrombocytosis is the increased risk of blood clots (thrombosis). These clots can obstruct blood flow in arteries and veins. Arterial thrombosis can lead to a heart attack or stroke, while venous thrombosis may appear as deep vein thrombosis (DVT) or a pulmonary embolism. Clots can also form in abdominal veins.
Paradoxically, despite the high platelet count, there is also an elevated risk of bleeding. This occurs because the platelets, while numerous, can be dysfunctional. An acquired form of von Willebrand disease can develop in patients with very high platelet counts, impairing the body’s ability to form a stable clot and leading to prolonged or spontaneous bleeding.
Diagnostic Evaluation
The diagnostic process for polycythemia vera and associated thrombocytosis involves several key tests. These evaluations help confirm the diagnosis and rule out other blood disorders.
- A complete blood count (CBC) is the initial test, which reveals an elevated red blood cell count (indicated by high hemoglobin and hematocrit) and a platelet count above the normal range.
- A peripheral blood smear is often performed, where a specialist examines a blood sample under a microscope to observe the physical characteristics of the blood cells.
- Genetic testing is used to detect the specific mutation responsible for the disease. Molecular analysis of the blood looks for the JAK2 V617F mutation, and its presence is a major criterion for diagnosis.
- A bone marrow aspiration and biopsy may be necessary. This procedure involves examining a small sample of bone marrow, which reveals overproduction of red blood cell precursors and an increased number of megakaryocytes. This test is not always required if other findings are conclusive.
Management and Treatment Strategies
The management of polycythemia vera with thrombocytosis is centered on reducing the risk of complications like blood clots and bleeding. A primary strategy is anti-platelet therapy, and most patients are prescribed a daily low-dose aspirin. Aspirin makes platelets less sticky, inhibiting their ability to form clots.
Controlling the volume of red blood cells is another aspect of treatment, achieved through therapeutic phlebotomy. This process of removing blood is done regularly to lower the hematocrit to a target level below 45%, which decreases blood viscosity.
For patients with very high platelet counts or those at high risk for clotting, cytoreductive therapy is used to lower blood cell production. A common first-line treatment is the oral medication hydroxyurea, which reduces both platelet and red blood cell counts.
Other options are available for patients who cannot tolerate or do not respond to hydroxyurea. These include JAK inhibitors, such as ruxolitinib, which are targeted drugs that inhibit the overactive JAK-STAT pathway. Another option is interferon-alpha, a biological therapy that can help control cell counts.
Prognosis and Long-Term Monitoring
Polycythemia vera is a chronic condition that currently has no cure, but it is highly manageable for most individuals. With consistent and appropriate treatment, many people can live for a long time with the disease. Lifelong monitoring by a hematologist is necessary to manage the disease effectively. Regular follow-up appointments and blood tests allow for adjustments in treatment to keep cell counts within a safe range and maintain a good quality of life.
Over many years, the disease can sometimes evolve. A small percentage of patients may see their condition progress to myelofibrosis, which involves the development of scar tissue in the bone marrow. In rarer instances, there is a risk of the disease transforming into acute myeloid leukemia (AML), underscoring the importance of continuous medical supervision.