Polycythemia vera

American Family Physician,  May 1, 2004  by Brian J. Stuart,  Anthony J. Viera

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Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by an increased red blood cell mass (RCM), or erythrocytosis, which leads to hyperviscosity and an increased risk of thrombosis. Patients may present with complaints of pruritus after bathing, burning pains in the distal extremities (erythromelalgia), gastrointestinal disturbances, or nonspecific complaints such as weakness, headaches, or dizziness. Other patients are diagnosed after an incidental finding of an elevated hemoglobin and/or hematocrit level on a complete blood count.

The median age of patients diagnosed with PV is 60 years, although it can occur in persons in all age groups. (1) PV occurs with a slight predominance in men. A comprehensive review (1) reported the incidence of PV to be 2.3 per 100,000 persons per year. Therefore, a typical family physician can expect to make a diagnosis of PV once or twice during his or her career, and will often have at least one patient in his or her patient panel who carries the diagnosis. The seriousness of PV is underscored by the fact that the median survival in untreated symptomatic patients after diagnosis is six to 18 months. (2) With treatment, the median survival is more than 10 years. (2)

Diagnosis

PV should be suspected when hemoglobin and/or hematocrit levels are elevated (i.e., hemoglobin level greater than 18 g per dL [180 g per L] in white men and 16 g per dL [160 g per L] in blacks and women; hematocrit level greater than 52 percent (0.52) in white men and 47 percent (0.47) in blacks and women). (3) PV also should be suspected in patients with portal venous thrombosis and splenomegaly with or without thrombocytosis and leukocytosis. Other signs and symptoms are listed in Table 1. (1,4)

In making the diagnosis of PV, the physician must first exclude a secondary erythrocytosis. (5,6) Once a secondary cause is ruled out (Table 2 (7)), the diagnosis of PV is made using a combination of major and minor criteria defined by the Polycythemia Vera Study Group (PVSG). Although new diagnostic modalities have been developed, these criteria remain the standard method to diagnose PV. (8)

Major diagnostic criteria include increased RCM, normal oxygen saturation, and the presence of splenomegaly. The test for RCM is a nuclear medicine study involving autologous infusion of radio-labeled red blood cells followed by serial phlebotomy to determine distribution. Physicians may refer patients to a specialty laboratory for this study.

Changes to these diagnostic criteria have been proposed. For example, determinations of RCM, classically given in milliliters per kilogram (mL per kg), can be misleading if the patient is obese, because body fat is relatively avascular. The International Council for Standardization in Haematology (ICSH) has amended the RCM assessment, recommending distribution. Physicians may refer patients to a specialty laboratory for this study.

Changes to these diagnostic criteria have been proposed. For example, determinations of RCM, classically given in milliliters per kilogram (mL per kg), can be misleading if the patient is obese, because body fat is relatively avascular. The International Council for Standardization in Haematology (ICSH) has amended the RCM assessment, recommending the use of formulas incorporating body surface area, weight, gender, and plasma volume. (8-10) [Level of evidence: C, consensus opinion] A patient with PV could have low oxygen saturation levels, because it is possible to have both PV and an unrelated hypoxic disorder. (1) Palpable splenomegaly is an important physical finding and major criterion. However, palpation is only 58 percent sensitive for diagnosis (11) (i.e., if present, it will not be detected by examiners in 42 percent of cases). Specificity is much better. This lack of sensitivity has led to some discussion about the use of imaging techniques to answer the question, although such a finding by imaging might be relegated to the status of a minor criterion. (10) In addition, the minor criteria of leukocyte alkaline phosphatase (LAP) and serum vitamin [B.sub.12] and [B.sub.12] binding capacity may be dropped in the future because of inter-laboratory error regarding LAP and the unavailability of vitamin B12 binding capacity. (10) Furthermore, neither of these criteria is sensitive nor specific. (1) Nonetheless, the PVSG criteria remain the diagnostic standard.

Serum erythropoietin (EPO), bone marrow histopathology and karyotype, and the presence of endogenous erythroid colonies (EEC) have been proposed as diagnostic tests for PV. Because PV is an autonomous (i.e., EPO-independent) erythroid proliferation, serum EPO levels in PV are low or normal. (1,5) Low-serum EPO levels for PV have a sensitivity of 70 percent and a specificity of 90 percent. (1)

In PV, bone marrow displays characteristic histologic findings, (10) and clonal cytogenetic abnormalities can be detected. (5) Use of this test requires the availability of a histologist who is specially trained in marrow histology. Finally, EEC growth is based on the ability of erythroid cells from peripheral blood and bone marrow samples in PV to grow in vitro without the addition of EPO. (12,13) This unique finding, along with serum EPO levels, forms the basis for a new diagnostic approach, (5) but has the disadvantages of expense and limited availability. (10)