Autosomal dominant secondary polycythemia

Autosomal dominant secondary polycythemia (also known as autosomal dominant erythrocytosis) is a rare inherited condition characterized by an abnormally increased number of red blood cells (erythrocytosis) that is not caused by a primary bone marrow disorder. Unlike polycythemia vera, which is a myeloproliferative neoplasm, this condition results from inherited genetic variants that lead to increased erythropoietin (EPO) sensitivity or production, causing the body to produce excess red blood cells. The condition primarily affects the hematologic system, leading to elevated hemoglobin and hematocrit levels. Several genetic forms have been described, including mutations in genes involved in oxygen sensing pathways such as VHL (von Hippel-Lindau gene), EGLN1 (PHD2), EPAS1 (HIF-2α), and the EPO gene itself, all of which can be inherited in an autosomal dominant manner. Patients typically present with plethora (ruddy complexion), headaches, dizziness, fatigue, and an increased risk of thromboembolic events such as deep vein thrombosis, pulmonary embolism, or stroke due to elevated blood viscosity. Some individuals may be relatively asymptomatic and are identified incidentally through routine blood tests showing elevated hemoglobin or hematocrit. The severity of symptoms can vary considerably even within the same family. Management focuses on reducing the risk of thrombotic complications. Phlebotomy (therapeutic blood removal) is the mainstay of treatment, aimed at maintaining hematocrit levels within a safer range. Low-dose aspirin may be considered to reduce thrombotic risk. There is currently no curative therapy, and treatment is largely supportive and symptom-directed. Genetic counseling is recommended for affected families to inform relatives about the 50% risk of transmission to offspring with each pregnancy.

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