Polycythemia vera (PV) is a rare, slow-growing blood disorder where the bone marrow produces an excessive number of red blood cells, often accompanied by an increase in white blood cells and platelets. This overproduction causes the blood to thicken (hyperviscosity), which impairs blood flow and increases the risk of serious complications like blood clots, heart attack, or stroke. Diagnosing PV requires a systematic approach, moving from recognizing subtle physical signs to objective laboratory evidence and specialized genetic testing. This process ensures the correct identification of PV and its distinction from other causes of elevated red blood cell counts.
Recognizing Initial Symptoms and Physical Indicators
The initial signs of polycythemia vera are often non-specific, resembling symptoms of many common ailments, which can delay diagnosis. Patients frequently experience fatigue, headaches, and dizziness, consequences of thickened blood slowing circulation and reducing oxygen delivery to tissues.
A more telling symptom is pruritus, or intense itching, often triggered or worsened after exposure to warm water, such as a bath or shower. Some patients also report erythromelalgia, a painful, burning sensation in their hands or feet, often accompanied by reddish or bluish skin discoloration. During a physical examination, a physician may note facial plethora (a flushed appearance) and detect splenomegaly (an enlarged spleen).
Essential Laboratory Blood Tests
The first objective step in diagnosis involves a comprehensive blood count (CBC). Results typically show an elevated hematocrit (the percentage of red blood cells in the total blood volume) and a high hemoglobin level. Specifically, an increased red cell mass is suggested by a hemoglobin level greater than 16.5 g/dL in men or 16.0 g/dL in women, or a hematocrit over 49% in men or 48% in women.
The CBC often also reveals an increase in white blood cells (leukocytosis) and platelets (thrombocytosis). This overall increase in all three major blood cell lines is known as panmyelosis and reflects the general overactivity of the bone marrow. Iron studies are also performed because iron deficiency, which is common in PV, can mask the true extent of the red blood cell increase.
Another significant measurement is the serum erythropoietin (EPO) level, a hormone that stimulates red blood cell production. In most PV cases, the EPO level is conspicuously low or below the normal reference range. A low EPO level indicates that red cell overproduction is occurring independently of normal regulatory signals, helping distinguish PV from other causes of high red cell counts.
Genetic Markers and Confirmatory Procedures
To definitively confirm the diagnosis of polycythemia vera and establish its clonal nature, specialized molecular and tissue tests are required. The most important molecular test is for the Janus kinase 2 (JAK2) gene mutation, which is present in virtually all PV patients. The most common finding is the JAK2 V617F mutation, detected in over 95% of PV cases.
The JAK2 V617F mutation causes the JAK2 protein to be constantly active, leading to the uncontrolled growth and proliferation of blood cells without external growth factor signals. If the initial JAK2 V617F test is negative, specialized testing for other related mutations, such as those in JAK2 exon 12, is performed. Detecting either of these mutations, coupled with the blood count abnormalities, strongly supports the diagnosis of PV.
A bone marrow biopsy (BMB) is often the final piece of evidence, particularly when initial blood tests or genetic results are inconclusive. The BMB involves taking a small sample of the spongy tissue inside the bone for microscopic examination. This procedure allows for a direct assessment of the bone marrow’s cellularity, which in PV typically shows hypercellularity, meaning an abnormally high number of blood-forming cells.
The pathologist specifically looks for the characteristic pattern of increased production across all three cell lines, along with the presence of abnormal, clustered megakaryocytes (the cells that produce platelets). The synthesis of all these findings—symptoms, blood counts, low EPO, a JAK2 mutation, and characteristic bone marrow histology—allows physicians to meet established diagnostic criteria, such as those set by the World Health Organization, to confirm the diagnosis.