Group

Polycythemia is a hematologic condition characterized by an abnormal increase in red blood cell mass. This elevation in red cell volume thickens the blood, leading to a higher risk of clotting events, stroke, and other complications. Polycythemia can be either primary, as seen in polycythemia vera (PV), or secondary to other underlying conditions. Recent advances in diagnostic techniques and therapeutic approaches have significantly improved the management and prognosis of patients with polycythemia.

Types and Causes

Polycythemia is broadly categorized into primary and secondary forms. Primary polycythemia, most notably polycythemia vera, is a myeloproliferative neoplasm resulting from a mutation in the JAK2 gene. This mutation leads to uncontrolled production of red blood cells in the bone marrow, independent of the body’s oxygen needs.

Secondary polycythemia, on the other hand, results from external factors that stimulate erythropoietin (EPO) production, such as chronic hypoxia, tumors producing EPO (like renal cell carcinoma), or living at high altitudes. Additionally, relative polycythemia may occur due to reduced plasma volume, often linked to dehydration or stress, rather than an actual increase in red cell mass.

Clinical Presentation

Symptoms of polycythemia can be subtle and nonspecific, especially in early stages. Common symptoms include headache, dizziness, blurred vision, fatigue, and pruritus, particularly after a hot shower. More serious complications include thrombotic events such as deep vein thrombosis, myocardial infarction, and stroke. In PV, splenomegaly is a frequent finding due to extramedullary hematopoiesis.

Diagnostic Advances

Traditional diagnostic approaches rely on complete blood count (CBC) testing, blood smear analysis, and measurement of erythropoietin levels. A hallmark of PV is a low EPO level despite elevated hemoglobin or hematocrit. Bone marrow biopsy may also be performed for a definitive diagnosis, particularly when considering other myeloproliferative disorders.

A significant advance in diagnosis has been the identification of the JAK2 V617F mutation, found in over 95% of PV cases. This molecular marker has become a cornerstone in differentiating PV from secondary causes of polycythemia. Additional genetic testing for other mutations, such as CALR and MPL, can assist in cases where JAK2 is negative but clinical suspicion remains high.

Management Strategies

The management of polycythemia aims to reduce the risk of thrombotic events and control symptoms. For patients with PV, phlebotomy is often the first line of treatment. It reduces hematocrit levels and blood viscosity, thereby minimizing the risk of clot formation. The target hematocrit level is generally maintained below 45% in men and 42% in women.

Cytoreductive therapy is considered for high-risk patients—those over age 60 or with a history of thrombosis. Hydroxyurea is the most commonly used cytoreductive agent, though newer options like ruxolitinib, a JAK1/2 inhibitor, have emerged for patients who are intolerant or resistant to hydroxyurea. Ruxolitinib not only controls hematocrit but also helps reduce spleen size and alleviate symptoms.

In secondary polycythemia, addressing the underlying cause—such as improving oxygenation in chronic lung disease or removing EPO-secreting tumors—is crucial. Low-dose aspirin is often used to decrease clot risk, particularly in PV.

Future Directions

Research continues to focus on improving diagnostic accuracy and developing targeted therapies. New JAK inhibitors and agents targeting other pathways involved in myeloproliferation are under investigation. Moreover, advances in genomic profiling may soon allow for more personalized treatment plans and risk stratification.