Polycythemia vera (PV) is an uncommon yet serious blood disorder classified as a myeloproliferative neoplasm that primarily involves the excessive production of red blood cells by the bones marrow.

This overproduction leads to increased blood thickness and a higher risk of complications, especially blood clots.

Pathophysiology and Etiology

Polycythemia vera stems from a clonal proliferation of hematopoietic stem cells in the bones marrow, leading to the abnormal elevation of red blood cells. Additionally, some patients experience increased production of white blood cells and platelets.

The majority of PV cases are linked to a mutation in the Janus kinase 2 (JAK2) gene, found in approximately 90% of patients, which causes cells to multiply uncontrollably even without normal growth signals.

Clinical Presentation and Symptoms

Many individuals with PV experience a slow disease progression, often showing no early symptoms. Most diagnoses occur incidentally during routine blood tests. When symptoms manifest, they tend to be diverse and can significantly impact quality of life. Common signs include persistent fatigue, headaches, dizziness, and blurred or double vision.

A striking symptom is intense itching, particularly after warm baths or showers, caused by abnormal histamine release from increased basophils. The skin may appear flushed or reddish due to hyperviscosity. Patients may also present with erythromelalgia—burning sensations and redness in the hands and feet.

Thrombosis, or blood clot formation, is a foreboding complication that can precipitate life-threatening events such as heart attacks and deep vein thrombosis. This risk is heightened by the thickened blood’s tendency to clot abnormally. Additionally, bleeding abnormalities can occur due to dysfunctional platelet levels.

Diagnostic Challenges

The diagnosis of polycythemia vera demands a comprehensive clinical and laboratory assessment. Key indicators include elevated red blood cell mass, increased hemoglobin and hematocrit levels, and the presence of the JAK2 mutation. Because PV affects multiple blood cell lines, white blood cell and platelet counts may also be elevated.

Complications and Long-Term Risks

Untreated or poorly managed PV presents significant health risks primarily associated with thrombosis and progression to more aggressive hematologic conditions. Blood clots can form in various, causing manifestations ranging from deep vein thrombosis to Budd-Chiari syndrome (hepatic vein thrombosis) and cerebrovascular accidents.

The disease may evolve into myelofibrosis, characterized by fibrotic scar tissue replacing functional, resulting in severe anemia and other cytopenias. There is also an increased risk of transformation to acute leukemia, although this is relatively rare. Chronic complications include gout, kidney stones, and ulcers, often linked to the metabolic disturbances caused by excess cell turnover.

Current Treatment Paradigms

Treatment strategies for polycythemia vera aim primarily at reducing hematocrit levels to prevent clot formation and alleviate symptoms. Phlebotomy, the regular removal of blood, is a mainstay to reduce red cell mass and blood viscosity. Low-dose aspirin is commonly prescribed to reduce clotting risk.

Cytoreductive agents such as hydroxyurea may be used to suppress bones marrow activity in higher-risk patients. Newer targeted therapies, including JAK2 inhibitors like ruxolitinib, offer promise in controlling disease manifestations and improving quality of life. Symptom management, including addressing itching, remains an essential aspect of care. Regular monitoring for disease progression and secondary complications is vital for long-term management.

"We have to get away from the concept of 'benign' hematology. There is nothing benign about living with polycythemia vera. The symptom burden is significant and the risk of transformation is real." — Dr. Ruben Mesa

Polycythemia vera is a rare but consequential blood disorder marked by uncontrolled red blood cell production that thickens the blood and predisposes affected individuals to serious vascular complications. Though it can remain silent for years, when symptoms arise, they vary widely and can significantly impair daily functioning.

A comprehensive diagnostic approach incorporating molecular testing is essential for definitive diagnosis and guiding treatment.

Advances in targeted therapies promise improved outcomes, yet vigilant management focusing on thrombotic risk reduction and symptom control remains fundamental. Understanding the complexities of PV helps medical professionals and patients alike navigate this challenging condition with informed care and hope for better prognoses.