- Author: Srikanth Nagalla, MBBS, MS, FACP; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP more...
Polycythemia vera (PV) is a stem cell disorder characterized as a panhyperplastic, malignant, and neoplastic marrow disorder. Its most prominent feature is an elevated absolute red blood cell mass because of uncontrolled red blood cell production.
Signs and symptoms
Impaired oxygen delivery due to sludging of blood may lead to the following symptoms:
Bleeding complications, seen in approximately 1% of patients with PV, include epistaxis, gum bleeding, ecchymoses, and gastrointestinal (GI) bleeding. Thrombotic complications (1%) include venous thrombosis or thromboembolism and an increased prevalence of stroke and other arterial thromboses.
Physical examination findings may include the following:
Splenomegaly (75% of patients)
According to 2008 revised World Health Organization (WHO) guidelines, diagnosis of PV requires the presence of both major criteria and one minor criterion or the presence of the first major criterion together with two minor criteria.
Major WHO criteria are as follows:
- Hemoglobin > 18.5 g/dL in men and > 16.5 g/dL in women, or other evidence of increased red blood cell volume
- Presence of JAK2617V F or other functionally similar mutation, such as JAK2 exon 12 mutationMinor WHO criteria are as follows:
See the list below:
Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation
Serum erythropoietin level below the reference range for normal
Endogenous erythroid colony formation in vitro
Treatment measures are as follows:
Phlebotomy – To keep hematocrit below 45%
Aspirin – 81 mg daily
Cytoreductive therapy – For patients at high risk for thrombosis
Splenectomy in patients with painful splenomegaly or repeated episodes of splenic infarction
Hydroxyurea is the most commonly used cytoreductive agent. If hydroxyurea is not effective or not tolerated, alternatives include the following:
Busulfan – In patients older than 65 years
Polycythemia vera (PV) is a stem cell disorder characterized as a panhyperplastic, malignant, and neoplastic marrow disorder. Its most prominent feature 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]
For discussion of polycythemia in children, see Pediatric Polycythemia vera.
Normal stem cells are present in the bone marrow of patients with polycythemia vera (PV), but 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 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 pathogenesis, as JAK2 is directly involved in the intracellular signaling following exposure to cytokines to which polycythemia vera progenitor cells display hypersensitivity. A recurrent unique acquired clonal mutation in JAK2 has been found in most patients with polycythemia vera 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. The substitution, called JAK2V617F, 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.
Thrombosis and bleeding are frequent in persons with polycythemia vera, as a result of 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 platelet 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.
Hyperhomocystinemia is a risk factor for thrombosis and is also widely prevalent in patients with MPD (35% in controls, 56% in persons with polycythemia vera).
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 from the syndrome.
Polycythemia vera (PV) is relatively rare, occurring in 0.6-1.6 persons per million population.
Race-, Sex-, and Age-related Demographics
Originally, Jewish persons were thought to have a higher predilection for polycythemia vera than members of other ethnic groups. Subsequently, however, many studies have shown that this condition occurs in all ethnic groups.
Polycythemia vera has no sex predilection, although the Polycythemia Vera Study Group (PVSG) found that slightly more males than females are affected.
The peak incidence of polycythemia vera is age 50-70 years. However, this condition occurs in persons of all age groups, including early adulthood and childhood, albeit rarely.
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