What are the complications of longstanding untreated Polycythemia (excessive red blood cell count)?

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Last updated: March 28, 2025 • View editorial policy

From the Guidelines

Longstanding untreated polycythemia can lead to several serious complications, including blood clots, hypertension, splenomegaly, bleeding problems, gout, pruritus, and hyperviscosity syndrome, with a significant risk of progression to myelofibrosis or transformation into acute leukemia. The most concerning complications include blood clots (thrombosis) that can cause strokes, heart attacks, deep vein thrombosis, or pulmonary embolism due to increased blood viscosity and platelet activation 1. Patients may develop hypertension as thicker blood increases resistance in blood vessels. Splenomegaly (enlarged spleen) often occurs as the spleen works harder to filter the excessive blood cells. Bleeding problems paradoxically develop despite increased blood cell counts, as abnormal platelet function and consumption of clotting factors create a bleeding tendency. Gout can develop from increased cell turnover leading to elevated uric acid levels. Patients may experience pruritus (itching), particularly after warm baths, due to histamine release from basophils.

Key Complications

  • Blood clots (thrombosis)
  • Hypertension
  • Splenomegaly (enlarged spleen)
  • Bleeding problems
  • Gout
  • Pruritus (itching)
  • Hyperviscosity syndrome
  • Progression to myelofibrosis or transformation into acute leukemia

According to the most recent study, targeting hematocrit levels to <45% can lower the risk of thrombosis, as demonstrated in the CYTO-PV trial, which randomized 365 adults with PV to either more intensive treatment (hematocrit <45%) or less intensive treatment (hematocrit 45%–50%) 1. The use of low-dose aspirin, as shown in the ECLAP trial, can safely reduce the risk of thrombotic complications in patients with PV. Treatment typically involves phlebotomy to reduce blood thickness, along with medications like hydroxyurea to suppress excess cell production, and low-dose aspirin to prevent clotting complications 2, 3.

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