Polycythemia Vera (PV)

At a Glance

Most patients being evaluated for polycythemia vera (PV) are incidentally discovered to have an increased hematocrit (>48% in women and >52% in men, respectively) and/or hemoglobin (>15 g/dL in women and >17 g/dL in men, respectively). Sustained expansion of the red cell mass, as seen in PV and other erythrocytoses, typically takes weeks or months to occur; thus, most PV patients are initially asymptomatic.

PV should also be suspected when the complete blood count (CBC) shows somewhat lower hematocrit/hemoglobin levels (either just outside the reference range or near the top of the reference range) accompanied by an elevated white blood cell count (>10,000/uL), especially with increased basophils on differential and/or platelet count (>450,000/uL) in the absence of infectious or inflammatory illness that could cause a reactive increase in these counts.

However, once the hemoglobin rises to 18-20 g/dL, patients generally become symptomatic and report:

chronic headaches

general malaise

easy fatigability

pruritus (often after showering)

Physical examination may demonstrate:

facial plethora (prominent and bloodshot eyes with red-purple mucous membranes)

dilated blood vessels of the conjunctiva and ocular fundus

splenomegaly

When the hemoglobin is greater than 20 g/dL, life-threatening conditions may occur, including:

venous and/or arterial thrombosis

hemorrhage (especially gastrointestinal (GI) when taking aspirin/NSAIDs)

Rarely, PV patients with chronic and sustained GI bleeding develop iron deficiency; such patients may have leukocytosis and/or thrombocytosis but a relatively normal hematocrit/hemoglobin. The laboratory clues to this situation are the hypochromia seen on peripheral smear and the low mean corpuscular volume (MCV). When such patients are not suspected of having PV, well-meaning but mistaken iron replacement therapy can rapidly cause symptomatic erythrocytosis.

Clinical findings or situations that would point the clinician away from PV and toward other causes of high hemoglobin/hematocrit include:

hypoxic diseases (especially pulmonary illness)

erythrocytosis at a younger age (especially in children)

patients living at high-altitudes

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Diagnostic criteria (World Health Organization (WHO) revised) for PV requires both major criteria and one minor criterion or one major criterion plus two minor criteria.

Major criteria:

Hemoglobin greater than 18.5 g/dL in men, greater than 16.5 g/dL in women, or increased red cell volume

JAK2 V617F mutation present or similar mutation in JAK2 exon 12

Minor criteria:

Blood—prominent leukocytosis or thrombocytosis and/or Marrow—hypercellularity of all cell lines with abnormal megakaryocytes

Serum Erythropoietin less than 4 mU/mL (or lower than reference range)

In vitro demonstration of endogenous erythroid colony (EEC) formation

Note that not all PV patients will have such an extreme elevation in hemoglobin as seen in Major Criterion 1. If there is a sustained increase of at least 2 g/dL from baseline values, hemoglobin values greater than 17 g/dL in men and greater than 15 g/dL in women fulfill the major criterion. Similarly, a red cell mass greater than 25% above the mean predicted normal value also suffices.

(Table 1)