Differential Diagnosis for Polycythemia Vera

When considering a diagnosis of polycythemia vera (PV), it's crucial to differentiate it from other conditions that may present with similar symptoms or laboratory findings. Here's a structured approach to the differential diagnosis:

• Single Most Likely Diagnosis

  • Primary Polycythemia Vera (PV): This is a myeloproliferative neoplasm characterized by the overproduction of red blood cells, white blood cells, and platelets. The presence of the JAK2 V617F mutation in the majority of cases, along with clinical features such as erythrocytosis, leukocytosis, thrombocytosis, and splenomegaly, supports this diagnosis.

• Other Likely Diagnoses

  • Secondary Polycythemia: Caused by chronic hypoxia (e.g., due to chronic obstructive pulmonary disease, sleep apnea, or living at high altitudes), which stimulates erythropoietin production, leading to increased red blood cell production.
  • Relative Polycythemia: Often seen in dehydration, where the concentration of red blood cells appears elevated due to decreased plasma volume rather than an absolute increase in red blood cell mass.
  • Essential Thrombocythemia (ET): Another myeloproliferative neoplasm that primarily presents with thrombocytosis but can sometimes mimic PV, especially if there's a significant increase in red blood cell mass.

• Do Not Miss Diagnoses

  • Chronic Myeloid Leukemia (CML): Although CML typically presents with leukocytosis and the presence of the BCR-ABL1 fusion gene, in some cases, it can mimic PV, especially in the early stages.
  • Paroxysmal Nocturnal Hemoglobinuria (PNH): A rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells, bone marrow failure, and the potential for thrombotic events. It's less likely but critical not to miss due to its severity and distinct management.
  • Erythrocytosis due to EPO Abuse: In individuals, especially athletes, who abuse erythropoietin (EPO) to enhance performance, leading to increased red blood cell production.

• Rare Diagnoses

  • Primary Myelofibrosis (PMF): A myeloproliferative neoplasm that can sometimes present with features overlapping with PV, including splenomegaly and teardrop poikilocytosis, but is distinguished by the presence of bone marrow fibrosis.
  • Hereditary Polycythemia: Caused by mutations in the EPO receptor or other genes involved in the hypoxia-sensing pathway, leading to congenital polycythemia. These conditions are rare and typically identified in familial cases or in individuals with a lifelong history of erythrocytosis.