Polycythemia Vera 

Polycythemia vera (PV) is a stem cell disorder characterized as a panhyperplastic, malignant, and neoplastic marrow disorder. The most prominent feature of this disease is an elevated absolute red blood cell mass because of uncontrolled red blood cell production. This is accompanied by increased white blood cell (myeloid) and platelet (megakaryocytic) production, which is due to an abnormal clone of the hematopoietic stem cells with increased sensitivity to the different growth factors for maturation.^{[1, 2, 3]}

Normal stem cells are present in the bone marrow of patients with polycythemia vera (PV). Also present are abnormal clonal stem cells that interfere with or suppress normal stem cell growth and maturation. Evidence indicates that the etiology of panmyelosis is unregulated neoplastic proliferation. The origin of the stem cell transformation remains unknown. See the image below.

Progenitors of the blood cells in these patients display abnormal responses to growth factors, suggesting the presence of a defect in a signaling pathway common to different growth factors. The observation that in vitro erythroid colonies grow when no endogenous erythropoietin (Epo) is added to the culture and the presence of a truncated Epo receptor in familial erythrocytosis indicate that the defect is in the transmission of the signal. The sensitivity of polycythemia vera (PV) progenitors to multiple cytokines suggests that the defect may lie in a common pathway downstream from multiple receptors. Increased expression of BCLX suggests an additional decrease in cellular apoptosis.

Several reasons suggest that a mutation on the Janus kinase-2 gene (JAK2) is the most likely candidate gene involved in polycythemia vera (PV) pathogenesis, as JAK2 is directly involved in the intracellular signaling following exposure to cytokines to which polycythemia vera (PV) progenitor cells display hypersensitivity.^[4] A recurrent unique acquired clonal mutation in JAK2 was found in most patients with polycythemia vera (PV) and other myeloproliferative diseases (MPDs) including essential thrombocythemia and idiopathic myelofibrosis.

A unique valine to phenylalanine substitution at position 617 (V617F) in the pseudokinase JAK2 domain has been identified called JAK2V617F that leads to a permanently turned on signaling at the affected cytokine receptors.^{[5, 6, 7, 8]} How these mutations interact with the wild type kinase genes and how they manifest into different forms of MPDs need to be elucidated.

Thromboses and bleeding are frequent in persons with polycythemia vera (PV) and MPD, and they result from the disruption of hemostatic mechanisms because of (1) an increased level of red blood cells and (2) an elevation of the platelet count. There are findings that indicate the additional roles of tissue factor and polymorphonuclear leukocytes (PMLs) in clotting, the platelet surface as a contributor to phospholipid-dependent coagulation reactions, and the entity of microparticles. Tissue factor is also synthesized by blood leukocytes, the level of which is increased in persons with MPD, which can contribute to thrombosis.

Rusak et al evaluated the hemostatic balance in patients using thromboelastography and also studied the effect of isovolemic erythrocytapheresis on patients with polycythemia vera. They concluded that thromboelastography may help to assess the thrombotic risk in patients with polycythemia vera.^[9]

Hyperhomocystinemia is a risk factor for thrombosis and is also widely prevalent in patients with MPD (35% in controls, 56% in persons with PV).

Acquired von Willebrand syndrome is an established cause of bleeding in persons with MPD, accounting for approximately 12-15% of all patients with this syndrome. von Willebrand syndrome is largely related to the absorption of von Willebrand factor onto the platelets; reducing the platelet count should alleviate the bleeding and the syndrome.

Frequency

United States

Polycythemia vera (PV) is relatively rare, occurring in 0.6-1.6 persons per million population.

Mortality/Morbidity

See Prognosis.

Race

Originally, Jewish individuals were thought to have a higher predilection for polycythemia vera (PV) than persons of other ethnic groups; however, many studies show that this condition occurs in persons of all ethnic groups.

Sex

Polycythemia vera (PV) has no sex predilection, although the Polycythemia Vera Study Group (PVSG) found that slightly more males are affected than females.^[3]

Age

The peak incidence of polycythemia vera (PV) is age 50-70 years. However, this condition occurs in persons of all age groups, including those in early adulthood and childhood, albeit rarely.