hematology and oncology
Polycythemia Vera
Diagnosis of Polycythemia Vera
Complete blood count (CBC) Testing forJAK2mutations,CALRmutations, orLNKmutations (done sequentially) Sometimes RBC mass determination, if available Polycythemia vera is often first suspected because of an abnormal CBC (eg, hemoglobin>16.5 g/dL [>165 g/L] in men or>16.0 g/dL [>160 g/L] in women). However, hemoglobin and hematocrit levels may be misleading. The hematocrit may be normal because of plasma volume expansion, and the hemoglobin may be normal if there is concurrent iron deficiency. Thus, an elevated red cell count is the most useful measure of erythrocytosis. Along with erythrocytosis, the neutrophil and platelet counts are usually, but not invariably, increased. Polycythemia vera can present with thrombocytosis alone due to masked erythrocytosis or because thrombocytosis occurs before erythrocytosis. In patients with only an elevated hematocrit, polycythemia vera may be present, but Secondary Erythrocytosis , a much more common cause of elevated hematocrit, must be considered first. Polycythemia vera should always be considered in patients with a normal hematocrit but microcytic erythrocytosis and Polycythemia vera may also be suspected based on clinical findings, including thrombosis in an unusual site, such as Budd-Chiari syndrome in women or portal vein thrombosis in men. The challenge in diagnosing polycythemia vera is that several other myeloproliferative neoplasms can have the same genetic mutations and bone marrow findings. Although the hallmark of polycythemia vera is erythrocytosis, some patients present with isolated leukocytosis or isolated thrombocytosis and do not initially manifest an elevated hematocrit level. Myeloproliferative neoplasms can evolve over time and even primary myelofibrosis can transform into polycythemia vera. Patients suspected of having polycythemia vera typically should have testing forJAK2V617F(exon 14) andJAK2exon12 mutations. If these results are negative, testing forCALRandLNKmutations is done. The presence of a known causative mutation in a patient with isolated erythrocytosis is strongly suggestive of polycythemia vera. If erythrocytosis isnotclearly present, direct measurement of red cell mass and plasma volume is done (eg, withchromium-labeled RBCs and 131-labeledalbuminalthough this test is usually available only at specialized centers) to help differentiate between true and relative polycythemia and between polycythemia vera and other myeloproliferative disorders (which do not have an increased red cell mass). If erythrocytosis is present but secondary causes have not been excluded, serumerythropoietinlevel should be measured. Patients with polycythemia vera typically have low or low-normal serumerythropoietinlevels; elevated levels suggest secondary erythrocytosis. Bone marrow aspirate and biopsy is not diagnostic of polycythemia vera. When done, bone marrow aspirate and biopsy typically shows panmyelosis, large and clumped megakaryocytes, and sometimes an increase in reticulin fibers. However, no bone marrow findings absolutely differentiate polycythemia vera from other disorders of excessive erythrocytosis (eg, congenital familial polycythemia) or from other myeloproliferative neoplasms, of which polycythemia vera is the most common. Acquired Von Willebrand Disease (as a cause of bleeding) may be diagnosed by showing decreased plasma Nonspecific laboratory abnormalities that may occur in polycythemia vera include elevated vitamin B12 and B12-binding capacity, hyperuricemia and hyperuricosuria (present in≥30% of patients), and decreased expression ofMPL(the receptor for thrombopoietin) in megakaryocytes and platelets. These tests are not needed for diagnosis. 