Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Disease Overview

The proposed revised World Health Organization criteria for the diagnosis of polycythemia vera (p. vera) requires two major criteria and one minor criterion or the first major criterion together with two minor criteria.[1]

Major Criteria

1. Hemoglobin of more than 18.5 g/dL in men, 16.5 g/dL in women, or elevated red cell mass greater than 25% above mean normal predicted value.
2. Presence of JAK2 617V greater than F or other functionally similar mutations, such as the exon 12 mutation of JAK2.

Minor Criteria

1. Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation.
2. Serum erythropoietin level below normal range.
3. Endogenous erythroid colony formation in vitro.

Other confirmatory findings no longer required for diagnosis include:[2,3,4]

• Oxygen saturation with arterial blood gas greater than 92%.
• Splenomegaly.
• Thrombocytosis (>400,000 platelets/mm³).
• Leukocytosis (>12,000/mm³).
• Leukocyte alkaline phosphatase (>100 units in the absence of fever or infection).

There is no staging system for this disease.

Patients have an increased risk of cardiovascular and thrombotic events and transformation to acute myelogenous leukemia or primary myelofibrosis.[5,6,7] Age older than 65 years and a history of vascular events are independent predictors of thrombosis.[5,8]

Treatment Overview

Therapy for p. vera includes intermittent, chronic phlebotomy to maintain the hematocrit below 45% in men.[9] The target level for women may need to be lower (e.g., hematocrit <40%), but there are no empiric data to confirm this recommendation.[10]

Complications of phlebotomy include:

• Progressive and sometimes extreme thrombocytosis and symptomatology related to chronic iron deficiency, including pica, angular stomatitis, and glossitis.
• Dysphagia that is the result of esophageal webs (very rare).
• Possibly muscle weakness.

(Refer to the Oral Complications of Chemotherapy and Head/Neck Radiation summary for more information.)

In addition, progressive splenomegaly or pruritus not controllable by antihistamines may persist despite control of the hematocrit by phlebotomy. (Refer to the Pruritus summary for more information.) If phlebotomy becomes impractical, hydroxyurea or interferon-alpha can be added to control the disease.

The Polycythemia Vera Study Group randomly assigned more than 400 patients to phlebotomy (target hematocrit <45), radioisotope phosphorous-32 (2.7 mg/m² administered intravenously every 12 weeks as needed), or chlorambucil (10 mg administered by mouth daily for 6 weeks, then given daily on alternate months).[11] The median survival for the phlebotomy group (13.9 years) and the radioisotope phosphorous-32 group (11.8 years) was significantly better than that of the chlorambucil group (8.9 years), primarily because of excessive late deaths from leukemia or other hematologic malignancies.[11][Level of evidence: 1iiA] Because of these concerns, many clinicians use hydroxyurea for patients who require cytoreductive therapy that is caused by massive splenomegaly, a high phlebotomy requirement, or excessive thrombocytosis.[11]