eMedicine Specialties > Pediatrics: General Medicine > Hematology

Polycythemia

Author: Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Coauthor(s): Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch; Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Contributor Information and Disclosures

Updated: Nov 2, 2009

Introduction

Background

Polycythemia is characterized by an increase in absolute quantity of red cells or total RBC volume. In contrast, relative polycythemia (pseudoerythrocytosis) is secondary to fluid loss or decreased fluid intake resulting in hemoconcentration. Two basic categories of polycythemia are recognized:

  • Primary polycythemias due to factors intrinsic to red cell precursors, including primary familial and congenital polycythemia (PFCP), idiopathic erythrocytosis, and polycythemia vera (PV).
  • Secondary polycythemias are caused by factors extrinsic to red cell precursors and include a physiologic-approproriate erythropoietin (epo) production in response to tissue hypoxia and physiologic-inappropriate erythropoietin production not in response to tissue hypoxia.

In normal hematopoiesis, myeloid stem cells give rise to erythrocytes, platelets, granulocytes, eosinophils, basophils, and monocytes. The production of each lineage is a function of cell proliferation, differentiation, and apoptosis. These various stages of differentiation rely on multiple interrelated processes. Protein growth factors, known as cytokines, stimulate proliferation of the multilineage cells (eg, interleukin [IL]-3, granulocyte-macrophage colony-stimulating activity [GM-CSF]). Other factors primarily stimulate the growth of committed progenitors (eg, GM-CSF, macrophage colony-stimulating factor [M-CSF], erythropoietin [Epo]).

Erythropoiesis is a carefully ordered sequence of events.

Bone marrow film at 400X magnification demonstrat...

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.

[ CLOSE WINDOW ]
Bone marrow film at 400X magnification demonstrat...

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.


Initially occurring in fetal hepatocytes, the process is taken over by the bone marrow in the child and adult. Although multiple cytokines and growth factors are dedicated to the proliferation of the RBC, the primary regulator is Epo. Red cell development is initially regulated by stem cell factor (SCF), which commits hematopoietic stem cells to develop into erythroid progenitors. Subsequently, Epo continues to stimulate the development and terminal differentiation of these progenitors. In the fetus, Epo is produced by monocytes and macrophages found in the liver. After birth, Epo is produced in the kidneys; however, Epo messenger RNA (mRNA) and Epo protein are also found in the brain and in RBCs, suggesting that some paracrine and autocrine function is present as well.

Erythropoiesis escalates as increased expression of the EPO gene produces higher levels of circulating Epo. EPO gene expression is known to be affected by multiple factors, including hypoxemia, transition metals (Co2+, Ni2+, Mn2+), and iron chelators. However, the major influence is hypoxia, including factors of decreased oxygen tension, RBC loss, and increased oxygen affinity of hemoglobin. In fact, Epo production has been observed to increase as much as 1000-fold in severe hypoxia.

Pathophysiology

Primary polycythemia is due to factors intrinsic to red cell precursors caused by acquired and inherited mutations. It includes the diagnoses of primary familial and congenital polycythemia, idiopathic erythrocytosis, and polycythemia vera.

Polycythemia vera, also known as polycythemia rubra vera, is a chronic clonal myleoproliferative disorder characterized by clonal proliferation of myeloid cells. Currently, the diagnosis of polycythemia vera is based on the 2008 World Health Organization (WHO) criteria, which has integrated molecular diagnostics into the evaluation and screening for polycythemia vera.1 A diagnosis of polycythemia vera is made when both major and one minor criterion are present or when the first major criterion is present with any two minor criteria. The current criteria include the following:

  • Major criteria
    1. Hemoglobin level of more than 18.5 g/dL in men (>16.5 g/dL in women) or other evidence of increased red cell volume

      or

      Hemoglobin or hematocrit level higher than 99th percentile of method-specific reference range for age, sex, altitude, of residence

      or

      Hemoglobin level of more than 17 g/dL in men (>15 g/dL in women) if associated with a documented and sustained increase of at least 2 g/dL from an individual’s baseline value that can not be attributed to correction of iron deficiency

      or

      Elevated red cell mass greater than 25% above mean normal predicted value
    2. Presence of JAK2V617F or similar mutation (eg, JAK2 exon 12 mutation)
  • Minor criteria
    1. Bone marrow trilineage myeloproliferation
    2. Subnormal serum Epo levels
    3. Endogenous erythroid colony growth

Earlier diagnostic criteria for polycythemia vera included the following (based on the Polycythemia Vera Study Group Diagnostic Criteria):2

  • Red cell mass greater than 36 mL/kg for men and greater than 32 mL/kg for women
  • Arterial oxygen saturation greater than 92%
  • Splenomegaly or 2 of the following:
    • Thrombocytosis greater than 400 X 109/L
    • Leukocytosis greater than 12 X 109/L
    • Leukocyte alkaline phosphatase activity greater than 100 U/L in adults (reference range, 30-120 U/L) without fever or infection
    • Serum vitamin B-12 greater than 900 pg/mL (reference range, 130-785 pg/mL)
    • Unsaturated vitamin B-12 binding capacity greater than 2200 pg/mL

Polycythemia vera is considered to be a form of the myeloproliferative syndromes that include polycythemia vera, essential thrombocythemia, and myelofibrosis (agnogenic myeloid metaplasia). The clonality of polycythemia vera is well established and was first demonstrated by Adamson et al in 1976.3 Subsequent studies suggest hypersensitivity of the myeloid progenitor cells to growth factors, including Epo, IL-3, SCF, GM-CSF, and insulinlike growth factor (IGF)–1, whereas other studies show defects in programmed cell death.

Until recently, the pathophysiology of polycythemia vera was unclear. In 2005, significant progress in the understanding of polycythemia vera was made with the discovery of a gain of function mutation in the tyrosine kinase JAK2 (JAK2V617F ), which now appears to cause most primary cases in adults.4,5,6,7,8 . JAK2V617F is detectable in more than 95% of patients diagnosed with polycythemia vera.9 Several other mutations of JAK2 have since been described (eg, exon 12, JAK2H538-K539delinsI ).10,11 The JAK2 mutations cause the enzyme to be constitutively active allowing cytokine independent proliferation of cell lines that express Epo receptors causing these cells to be hypersensitive to cytokines.9

Familial clustering suggests a genetic predisposition. Whether these mutations are responsible for the development of polycythemia vera in pediatric patients is unclear. Some groups have reported lower rates of JAK2 mutations in children compared with adults,12,13,14 whereas other groups have seen similar rates with complete or near complete presence of JAK2V617F and other JAK2 mutations.11 . The prevalence of familial cases of chronic myeloproliferative disease is thought to be at least 7.6%, and the pattern of inheritance is consistent with an autosomal dominant pattern with decreased penetrance. Evidence of disease anticipation is noted in the second generation, presenting at a significantly younger age. However, clinical and hematological features in familial cases have not been shown to differ from those of sporadic mutations.15

Primary familial and congenital polycythemia is caused by a mutation in the Epo receptor resulting in hypersensitivity to Epo. Several mutations (approximately 14) have been identified in the Epo receptor (EPOR) gene; however, EPOR mutations have not been identified in all PFCP kindreds. Most identified EPOR mutations (11) cause truncation of the c-terminal cytoplasmic receptor domain of the receptor. These truncated receptors have heightened sensitivity to circulating Epo due to a lack of negative feedback regulation.16 This autosomal dominant trait does not necessarily carry an adverse prognosis in early life but is associated with an increased risk of thrombotic and vascular mortality in later life.17

Chuvash polycythemia, a congenital polycythemia first recognized in an endemic Russian population, is a variant of primary familial and congenital polycythemia and has mutations in the von Hippel-Lindau (VHL) gene, which is associated with a mutation in the oxygen-sensing pathway that regulates Epo synthesis. Polycythemia outside of Russia found to have a similar mechanism is referred to as primary proliferative polycythemia.17

Secondary polycythemia may result from functional hypoxia induced by lung disease, heart disease, increased altitude (hemoglobin increase of 4% for each 1000-m increase in altitude), congenital methemoglobinemia, and other high–oxygen affinity hemoglobinopathies stimulating increased Epo production. Secondary polycythemia may also result from increased Epo production secondary to benign and malignant Epo-secreting lesions.

High altitude erythrocytosis is evident within the first week of high-altitude exposure. A sharp increase in Epo production is noticeable, with associated mobilization of iron stores with evidence of iron-deficient erythropoiesis.17

Abnormal high-affinity hemoglobin mutations characterized by left shift in the oxygen-hemoglobin dissociation curves lead to erythrocytosis. In most cases, no treatment is indicated for these patients because the erythrocytosis is compensatory. Similarly, in familial polycythemia with defects in 2,3-DPG metabolism, a left shift in the oxygen-hemoglobin curve is noted with a physiological response of polycythemia.17

Secondary polycythemia of the newborn is fairly common and is seen in 1-5% of all newborns in the United States. It results from either chronic or acute fetal hypoxia or delayed cord clamping and stripping of the umbilical cord.18

Aberrant erythropoietin production is seen with various renal, liver, CNS disorders and leads to physiologically inappropriate secondary polycythemia. Renal disorders frequently associated with polycythemia include renal cell carcinoma, Wilms tumor, polycystic kidneys, and renal transplantation. Erythrocytosis has also been documented in patients with hepatocellular carcinoma.

Frequency

United States

Primary polycythemia is rare; the overall prevalence of polycythemia vera is 22 cases per 100,000 people.19 The annual incidence of polycythemia vera is 2 cases per 100,000 people. The median age is 70 years,20 with only 0.1% of cases of polycythemia vera observed in individuals younger than 20 years. Fewer than 50 cases of pediatric polycythemia vera have been reported in the literature. Polycythemia vera is less likely in blacks than in individuals of European ancestry, with a higher incidence in Ashkenazi Jews.

International

Polycythemia vera has a similar incidence in Western Europe as in the United States, and occurrence rates are very low in Africa and Asia (as low as 2 cases per million per year in Japan).

Mortality/Morbidity

Death rates for children are unavailable. The complications found in polycythemia vera are related to 2 primary factors. The first includes complications related to hyperviscosity. The second involves bone marrow–related complications. Untreated, the median survival time for these patients is 18 months. However, if patients are treated, survival is greatly extended, as many as 10-15 years with phlebotomy alone. The causes of death in adults are as follows:

  • Thrombosis/thromboembolism (30-40%) -Myocardial infarctions, deep vein thrombosis, pulmonary embolus, portal splenic and mesenteric vein thrombosis
  • Acute myelogenous leukemia (19%)
  • Other malignancies (15%)
  • Hemorrhage (2-10%)
  • Myelofibrosis/myeloid metaplasia (4%)
  • Other (25%)

In the neonatal period, polycythemia-induced hyperviscosity can lead to altered blood flow and subsequently affect organ function. Infants with polycythemia are at increased risk for necrotizing enterocolitis, renal dysfunction, hypoglycemia, and increased pulmonary vascular resistance with resultant hypoxia and cyanosis. Although initially thought to cause neurologic dysfunction, the decrease in cerebral blood flow seen in newborns with polycythemia is a physiologic response and does not appear to cause cerebral ischemia.18

Race

In the United States, higher rates of polycythemia vera are observed in the Ashkenazi Jewish population, and lower rates are seen in blacks.

Sex

The male-to-female ratio is 1.2-2.2:1 in adults and 1:1 in children.17

Age

The median age for polycythemia vera is 70 years.20 Only 0.1% of polycythemia cases occur in people younger than 20 years.

Clinical

History

The clinical features associated with polycythemia are a direct result of the increase in red cell mass, which causes an expansion of blood volume. Signs of hyperviscosity and increased metabolism accompany polycythemia. A thorough history must be obtained for a history of cardiac, pulmonary (including sleep apnea), hepatic or renal disease in the patient and a complete family history for evidence of familial polycythemia.

Symptoms include the following:

  • Headache, vertigo, insomnia
  • Weakness or malaise
  • Pruritus (especially after exposure to warm water)
  • Bruising
  • Ruddy or red appearance
  • Erythromelalgia (burning pain, warmth, and redness of extremities)
  • Diaphoresis/dyspnea
  • Visual disturbance
  • Ringing in the ears
  • Paresthesias
  • Arthropathies
  • Weight loss
  • GI - Fullness, thirst, abdominal discomfort, constipation

Physical

A thorough physical examination must be completed and include specific evaluation for signs and symptoms of underlying disease that may cause secondary polycythemia; it must include pulse oximetry, careful cardiac and pulmonary evaluation, and evaluation for signs of renal or hepatic disease.

Signs of polycythemia include the following:

  • Rubor, especially facial rubor and sparing of the trunk
  • Skin plethora
  • Hypertension, both systolic and diastolic
  • Hepatomegaly
  • Splenomegaly - Usually feels hard and smooth and occurs in more than two thirds of patients
  • Conjunctival plethora (engorged vessels in the bulbar conjunctiva)
  • Ecchymosis
  • Cardiac hypertrophy (rarely observed)

Causes

  • Primary polycythemia (due to factors intrinsic to the red cell precursors)
    • In the past, the pathophysiology was unclear, and primary polycythemias were thought to be due to both inherited and acquired mutations in erythroid progenitors, leading to abnormal red cell proliferation. However, in 2005, an activating mutation found in the tyrosine kinase JAK2 was implicated as the causative factor in polycythemia vera (PV). This mutation is found in more than 95% of patients with polycythemia vera.9
    • The JAK2 V617F mutation is a point mutation that causes a substitution of phenylalanine for valine in exon 14. The mutation causes the enzyme to be constitutively active, allowing cytokine-independent proliferation of cell lines that express erythropoietin receptors, causing these cells to be hypersensitive to cytokines. This mutation is seen in polycythemia vera, essential thrombocythemia, and primary myelofibrosis.9
    • Additional JAK2 mutations have been identified in exon 12,10 JAK2H538-K539delinsI ,21 and others.22 . Exon 12 JAK2 mutations appear specific for polycythemia vera and idiopathic erythrocytosis.9
    • Patients with primary familial and congenital polycythemia (PFCP) are commonly found to have mutations in the Epo receptor (EPOR) gene. Approximately 14 mutations have been identified.
    • Chuvash polycythemia, a congenital polycythemia first recognized in an endemic Russian population, has mutations in the von Hippel-Lindau (VHL) gene, which is associated with a perturbed oxygen-dependent regulation of Epo synthesis.
  • Secondary polycythemia (caused by factors extrinsic to red cell precursors that lead to insufficient oxygen supply to tissues)
    • High-altitude erythrocytosis
    • Pulmonary disease - Chronic obstructive pulmonary disease, diffuse pulmonary infiltrates, kyphoscoliosis, chronic cor pulmonale
    • Cyanotic heart disease
    • Hypoventilation syndromes -Obstructive sleep apnea
    • Epo-secreting tumors - Renal cell carcinoma, hepatocellular carcinoma
  • Polycythemia of the newborn - Usually results from a poor intrauterine environment or hypoxic insult during labor or delivery
  • Congenital causes - High-affinity hemoglobin and 2,3-Bisphosphoglycerate (2,3-BPG) deficiency

More on Polycythemia

Overview: Polycythemia
Differential Diagnoses & Workup: Polycythemia
Treatment & Medication: Polycythemia
Follow-up: Polycythemia
Multimedia: Polycythemia
References
[ CLOSE WINDOW ]

References

  1. [Guideline] Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. Aug 15 2007;110(4):1092-7. [Medline].

  2. Streiff MB, Smith B, Spivak JL. The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood. Feb 15 2002;99(4):1144-9. [Medline].

  3. Adamson JW, Fialkow PJ, Murphy S, et al. Polycythemia vera: stem-cell and probable clonal origin of the disease. New England Journal of Medicine. 1976;295:913-916. [Medline].

  4. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. Apr 28 2005;434(7037):1144-8. [Medline].

  5. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. Apr 28 2005;352(17):1779-90. [Medline]. [Full Text].

  6. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. Apr 2005;7(4):387-97. [Medline].

  7. Vainchenker W, Constabtinescu S. A Unique Activating Mutation in JAK2 (V617F) Is at the Origin of Polycythemia Vera and Allows a New Classification of Myeloproliferative Diseases. Hematology. 2005;195-200. [Medline]. [Full Text].

  8. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem. Jun 17 2005;280(24):22788-92. [Medline].

  9. Tefferi A. JAK2 mutations in polycythemia vera--molecular mechanisms and clinical applications. N Engl J Med. Feb 1 2007;356(5):444-5. [Medline].

  10. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. Feb 1 2007;356(5):459-68. [Medline].

  11. Cario H, Pahl HL, Schwarz K, et al. Familial polycythemia vera with Budd-Chiari syndrome in childhood. Br J Haematol. Oct 2003;123(2):346-52. [Medline].

  12. Teofili L, Foa R, Giona F, Larocca LM. Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients?. Haematologica. Feb 2008;93(2):169-72. [Medline].

  13. Teofili L, Giona F, Martini M, et al. Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol. Mar 20 2007;25(9):1048-53. [Medline].

  14. Rives S, Pahl HL, Florensa L, Bellosillo B, Neusuess A, Estella J. Molecular genetic analyses in familial and sporadic congenital primary erythrocytosis. Haematologica. May 2007;92(5):674-7. [Medline].

  15. Rumi E, Passamonti F, Della Porta MG, et al. Familial chronic myeloproliferative disorders: clinical phenotype and evidence of disease anticipation. J Clin Oncol. Dec 10 2007;25(35):5630-5. [Medline].

  16. Cario H. Childhood polycythemias/erythrocytoses: classification, diagnosis, clinical presentation, and treatment. Ann Hematol. Mar 2005;84(3):137-45. [Medline].

  17. Greer JP, Foerster J, Rodgers GM, et al. Erthrocytosis. In: Pine JW, Jacobs AE,. Wintrobe's Clinical Hematology. Twelfth. Lippincott, Williams and Wlkins; 2009.

  18. Sarkar S, Rosenkrantz TS. Neonatal polycythemia and hyperviscosity. Semin Fetal Neonatal Med. Aug 2008;13(4):248-55. [Medline].

  19. Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol. May 2008;83(5):359-62. [Medline].

  20. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. Apr 2006;32(3):171-3. [Medline].

  21. Cario H, Schwarz K, Herter JM, Komrska V, McMullin MF, Minkov M. Clinical and molecular characterisation of a prospectively collected cohort of children and adolescents with polycythemia vera. Br J Haematol. Aug 2008;142(4):622-6. [Medline].

  22. Smith CA, Fan G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum Pathol. Jun 2008;39(6):795-810. [Medline].

  23. McMullin MF, Bareford D, Campbell P, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol. Jul 2005;130(2):174-95. [Medline].

  24. Landolfi R, Marchioloi R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. New England Journal of Medicine. 2004;350:114-124. [Medline]. [Full Text].

  25. Zhan H, Spivak JL. The diagnosis and management of polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the JAK2 V617F era. Clin Adv Hematol Oncol. May 2009;7(5):334-42. [Medline].

  26. Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. Oct 15 2008;112(8):3065-72. [Medline].

  27. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. Mar 19-25 2005;365(9464):1054-61. [Medline].

  28. Ebert BL, Bunn HF. Regulation of the erythropoietin gene. Blood. Sep 15 1999;94(6):1864-77. [Medline]. [Full Text].

  29. Gomella TL, Cunningham MD, Eyal FG, eds. Neonatal polycythemia. In: Neonatology: Management, Procedures, On-call Problems, Diseases and Drugs. 3rd ed. Norwalk, CT: Appleton & Lange; 1994.

  30. Goyal RK, Longmore GD. Abnormalities of cytokine receptor signalling contributing to diseases of red blood cell production. Ann Med. Jun 1999;31(3):208-16. [Medline].

  31. Grier HE, Civin CI. Polycythemia vera. In: Orkin, SH, Oski FA eds. Nathan and Oski's Hematology of Infancy and Childhood. Vol 2. 5th ed. Philadelphia, PA: WB Saunders Co; 1998:1307-8.

  32. Hoffman R. Polycythemia. Hematology: Basic Principles and Practice. 3rd ed. 2000;Chapter 61:1130-1151.

  33. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:1-351.

  34. Johansson PL, Safai-Kutti S, Kutti J. An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: a study of patients with polycythaemia vera and apparent polycythaemia. Br J Haematol. Jun 2005;129(5):701-5. [Medline].

  35. Jones AV, Silver RT, Waghorn K, et al. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha. Blood. Apr 15 2006;107(8):3339-41. [Medline].

  36. Kralovics R, Prchal JT. Congenital and inherited polycythemia. Curr Opin Pediatr. Feb 2000;12(1):29-34. [Medline].

  37. Kwaan HC, Wang J. Hyperviscosity in polycythemia vera and other red cell abnormalities. Semin Thromb Hemost. Oct 2003;29(5):451-8. [Medline].

  38. Lee GR, Paraskevas F, Foerster John, eds. Polycythemia vera. In: Wintrobe's Clinical Hematology. 10th ed. Baltimore, MD: Williams & Wilkins; 1999:2380-5.

  39. Nelson WE, Behrman RE, Kliegman R, eds. Polycythemia vera. In: Nelson's Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders; 1996.

  40. Pappas A, Delaney-Black V. Differential diagnosis and management of polycythemia. Pediatric Clinics of North America. 2004;51:1063-86. [Medline].

  41. Passamonti F, Malabarba L, Orlandi E, et al. Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia. Haematologica. Jan 2003;88(1):13-8. [Medline].

  42. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. Nov 15 2004;117(10):755-61. [Medline].

  43. Pizzo PA, Poplack DG, eds. Myleoproliferative disorders. In: Principles and Practice of Pediatric Oncology. 4th ed. 2002:627.

  44. Prchal JF, Prchal JT. Molecular basis for polycythemia. Curr Opin Hematol. Mar 1999;6(2):100-9. [Medline].

  45. Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera. J Clin Oncol. Oct 13 2009;[Medline].

  46. Rosenkrantz TS. Polycythemia and hyperviscosity in the newborn. Seminars in Thrombosis and Hemostasis. 2003;29:515-527. [Medline].

  47. Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. Dec 15 2002;100(13):4272-90. [Medline]. [Full Text].

  48. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood. Jul 15 2008;112(2):231-9. [Medline].

  49. Tefferi A. Essential thrombocythemia, polycythemia vera, and myelofibrosis: current management and the prospect of targeted therapy. Am J Hematol. Jun 2008;83(6):491-7. [Medline].

  50. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. Jan 2008;22(1):14-22. [Medline].

  51. Walters MC, Abelson HT. Interpretation of the complete blood count. Pediatr Clin North Am. Jun 1996;43(3):599-622. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

polycythemia vera, PV, polycythemia rubra vera, erythrocytosis, absolute erythrocytosis, relative erythrocytosis, familial erythrocytosis, primary familial and congenital polycythemia, PFCP, primary familial polycythemia, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Disclosure: Nothing to disclose.

Coauthor(s)

Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch
Disclosure: Nothing to disclose.

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.