hematology and oncology
Polycythemia Vera
Pathophysiology of Polycythemia Vera
Polycythemia vera involves increased production of red blood cells (RBCs), white blood cells (WBCs), and platelets. Thus, polycythemia vera is a panmyelosis because of increases of all 3 peripheral blood components. Increased production confined to the RBC line is termed erythrocytosis; isolated erythrocytosis may occur with polycythemia vera but is more commonly due to other causes (see Secondary Erythrocytosis ). In polycythemia vera, RBC production proceeds independently of the serum Extramedullary hematopoiesis may occur in the spleen, liver, and other sites that have the potential for blood cell formation. In polycythemia vera, in contrast to secondary erythrocytosis, the red cell mass increase is often initially masked by an increase in the plasma volume that leaves the hematocrit in the normal range. This is particularly the case in women, who can present with hepatic vein thrombosis and a normal hematocrit. In polycythemia vera, iron absorption is increased due to suppression of hepcidin production. In the presence of Iron Deficiency Anemia of any kind, RBCs become increasingly smaller (microcytosis) because the red cell hemoglobin concentration (MCHC) is defended at the expense of red cell volume (mean corpuscular volume [MCV]). Although patients with iron deficiency from other causes become anemic, patients with polycythemia vera have increased RBC production and thus, even when iron-deficient initially patients with polycythemia vera can have a Eventually, about 10 to 15% of patients progress to a syndrome similar to Primary Myelofibrosis (PMF) but with a better survival. Transformation to Acute leukemias is rare and may take many years to develop. The risk of transformation is increased with exposure to alkylating agents, such as Polycythemia vera is caused by a mutation in an hematopoietic stem cell. Mutations of the Janus kinase 2 (JAK2) gene are responsible in most cases of polycythemia vera. JAK2 is a member of the class I type of tyrosine kinase family of enzymes and is involved in signal transduction forerythropoietin, thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors. Specifically, theJAK2V617Fmutation or theJAK2exon12 mutation is present in 95% of patients with polycythemia vera. Calreticulin (CALR) mutations have been found rarely in patients with polycythemia vera who lack aJAK2mutation, and lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis. These mutations lead to sustained activation of the JAK2 kinase, which causes excess blood cell production independent oferythropoietin. Complications of polycythemia vera include Thrombosis Bleeding In polycythemia vera, the blood volume expands and the increased number of RBCs can cause hyperviscosity. Hyperviscosity predisposes to macrovascular thrombosis, resulting in Overview of Stroke , because the platelets adsorb and proteolyze high molecular weight von Willebrand multimers. This acquired Von Willebrand Disease predisposes to increased, but not spontaneous, bleeding. Increased cell turnover may cause hyperuricemia, increasing the risk of Gout and urate kidney stones. Patients with polycythemia vera are prone to acid-peptic disease due to 