History
Symptoms of polycythemia vera (PV) are often insidious in onset, and they are often related to blood hyperviscosity secondary to a marked increase in the cellular elements of blood. Subsequent sludging of blood flow and thrombosis lead to poor oxygen delivery, with symptoms that include the following:
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Headache
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Dizziness
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Vertigo
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Tinnitus
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Visual disturbances
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Angina pectoris
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Intermittent claudication
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.
Abdominal pain due to peptic ulcer disease may be present because PV is associated with increased histamine levels and gastric acidity or possible Budd-Chiari syndrome (hepatic portal vein thrombosis) or mesenteric vein thrombosis. Early satiety can occur in patients with splenomegaly, because of gastric filling being impaired by the enlarged spleen or, rarely, as a symptom of splenic infarction. Weight loss may result from early satiety or from the increased myeloproliferative activity of the abnormal clone.
Pruritus results from increased histamine levels released from increased basophils and mast cells and can be exacerbated by a warm bath or shower. This occurs in up to 40% of patients with PV.
Physical
Physical findings in patients with polycythemia vera (PV) are due to the myeloproliferative process and excess concentrations of the cellular elements of blood with extramedullary hematopoiesis. Splenomegaly is present in 75% of patients at the time of diagnosis. Hepatomegaly is present in approximately 30% of patients.
Plethora or a ruddy complexion is characteristic of PV and results from the marked increase in total red blood cell mass. This manifests in the face, palms, nailbeds, mucosa, and conjunctiva.
Hypertension is common in patients with PV. Measurement of the red blood cell mass should differentiate this condition from Gaisbock syndrome, which is hypertension and pseudopolycythemia (ie, high hemoglobin levels due to low plasma volume).
Causes
The causes of polycythemia vera (PV) are unknown, but a number of approaches are now being studied to define the molecular lesion or lesions. The JAK2 V617F mutation can give rise to a turned-on cytokine receptor, leading to pancytosis similar to the PV phenotype. This is similar to the biologic properties of the BCR/ABL abnormality in that they both mimic cytokine signaling.
Clonality studies using a rare polymorphism in the G6PD gene demonstrate predominant expression of a single allele in all blood cell lines. X-chromosome inactivation studies have played a pivotal role in establishing current concepts of many hematologic malignancies. Approximately 90% of patients with PV show a skewed pattern of X inactivation in all their blood cell lines, indicating support for the concept of a transformed multipotential stem cell.
Cytogenetic studies show the presence of an abnormal karyotype in the hematopoietic progenitor cells in approximately 34% of patients with PV, depending on which stage of the disease the study was performed at. Approximately 20% of patients have cytogenetic abnormalities at diagnosis, increasing to more than 80% for those with more than 10 years of follow-up care.
The following genetic abnormalities, which are similar to the abnormal karyotypes observed in patients with myelodysplastic syndromes and other MPDs, have been observed in patients with PV:
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Deletion of 20q (8.4%)
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Deletion of 13q (3%)
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Trisomy 8 (7%)
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Trisomy 9 (7%)
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Trisomy of 1q (4%)
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Deletion of 5q or monosomy 5 (3%)
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Deletion of 7q or monosomy 7 (1%)
Spivak and colleagues analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with PV and found twice as many up-regulated or down-regulated genes in men as in women. In addition, these researchers found 102 genes with differential regulation that was concordant in men and women and that could be used to divide patients into two phenotypical groups. The groups differed significantly with respect to disease duration, clinical manifestations, and prognosis. [14]
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Bone marrow film at 100X magnification demonstrating hypercellularity and increased number of megakaryocytes. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Blood film at 400X magnification demonstrating polyglobulia and thrombocytosis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Bone marrow film at 400X magnification demonstrating dominance of erythropoiesis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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This blood film at 10,000X magnification shows a giant platelet and an eosinophil. Erythrocytes show signs of hypochromia as a result of repeated phlebotomies. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
