13-24: Polycythemia Vera

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Polycythemia vera is an acquired myeloproliferative disorder that causes overproduction of all three hematopoietic cell lines, most prominently the RBCs. Erythroid production is independent of erythropoietin, and the serum erythropoietin level is low. True erythrocytosis, with an elevated RBC mass, should be distinguished from spurious erythrocytosis caused by a constricted plasma volume.

A mutation in exon 14 of JAK2 (V617F), a signaling molecule, has been demonstrated in 95% of cases. Additional JAK2 mutations have been identified (exon 12) and suggest that JAK2 is involved in the pathogenesis of this disease and is a therapeutic target.

CLINICAL FINDINGS

A. Symptoms and Signs

Headache, dizziness, tinnitus, blurred vision, and fatigue are common complaints related to expanded blood volume and increased blood viscosity. Generalized pruritus, especially following a warm shower or bath, is related to histamine release from the basophilia. Epistaxis is related to engorgement of mucosal blood vessels in combination with abnormal hemostasis. Sixty percent of patients are men, and the median age at presentation is 60 years. Polycythemia rarely occurs in persons under age 40 years.

Physical examination reveals plethora and engorged retinal veins. The spleen is palpable in 75% of cases but is nearly always enlarged when imaged. Thrombosis is the most common complication of polycythemia vera and the major cause of morbidity and death in this disorder. Thrombosis appears to be related both to increased blood viscosity and abnormal platelet function. Uncontrolled polycythemia leads to a very high incidence of thrombotic complications of surgery, and elective surgery should be deferred until the condition has been treated. Paradoxically, in addition to thrombosis, increased bleeding can occur. There is also a high incidence of peptic ulcer disease.

B. Laboratory Findings

According to the WHO 2016 criteria, the hallmark of polycythemia vera is a hematocrit (at sea level) that exceeds 49% in males or 48% in females. RBC morphology is normal (Table 13–14; see RBCs in eFigure 13–1). The white blood count is usually elevated to 10,000–20,000/mcL (10–20 × 10⁹/L), and the platelet count is variably increased, sometimes to counts exceeding 1,000,000/mcL (1000 × 10⁹/L). Platelet morphology is usually normal. WBCs are usually normal, but basophilia and eosinophilia are frequently present. Erythropoietin is suppressed and serum levels, usually low. The diagnosis should be confirmed with JAK2 mutation screening. The absence of a mutation in either exon 14 (most common) or 12 should lead the clinician to question the diagnosis.

The bone marrow is hypercellular, with hyperplasia of all hematopoietic elements, but bone marrow examination is not necessary to establish the diagnosis. Iron stores are ...