Pediatric Polycythemia Vera Clinical Presentation

  • Author: Josef T Prchal, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Apr 13, 2012
 

History

Polycythemia vera (PV) frequently comes to the attention of clinicians because of an elevated hematocrit level found on routine laboratory testing. Some patients are asymptomatic, whereas others have various nonspecific symptoms that are recognized in the context of polycythemia vera. Thirty percent of patients report headache, weakness, dizziness, and sweating (in order of decreasing frequency). Many of these symptoms can be attributed to excess hematocrit.

Alternatively, the patient may present with a complication of polycythemia vera. Approximately 33% of patients present with thrombosis or hemorrhage; 75% of these have arterial thrombosis, and 25% have venous thrombosis. Cerebrovascular accidents, myocardial infarction, deep venous thrombosis, and pulmonary embolism (in order of decreasing frequency) can result from thrombosis due to polycythemia vera.

Budd-Chiari syndrome (hepatic vein thrombosis) is less common in polycythemia vera but is more specific to it. A patient who presents with Budd-Chiari syndrome should alert the physician to consider polycythemia vera because it is the most common underlying disease. Approximately 2-10% of patients with polycythemia vera have Budd-Chiari syndrome. Many presenting patients do not have an elevated hematocrit at the time of presentation but have other polycythemia vera laboratory abnormalities; if they survive, they eventually develop a myeloproliferative phenotype. One study of 41 patients with idiopathic Budd-Chiari syndrome found that 58% of these patients had the JAK2V617F mutation.[10] Another group reported that patients with Budd-Chiari syndrome and the JAK2V617F mutation can have an elevatedserum erythropoietin(Epo) level.[11] Classically, the presence of anelevated Epo level was believed to make the diagnosis of polycythemia veraextremely unlikely.

Less than 5% of patients have erythromelalgia (ie, erythema and warmth of the distal extremities, especially of the hands and feet, with a painful burning sensation that can result in digital ischemia if prolonged). A role for platelet aggregation has been proposed; in fact, the syndrome responds frequently (but not always) within hours to low-dose aspirin therapy.

Less commonly, polycythemia vera presents with cardiovascular symptoms due to myocardial infarction and congestive heart failure, pulmonary hypertension from chronic thromboembolic disease, neurological symptoms due to spinal cord compression by extramedullary hematopoiesis, and elevated uric acid with subsequent gout due to increased cell turnover.

Unrecognized hepatic or splenic vein thrombosis can result in portal hypertension and varices. Other GI symptoms include peptic ulcer disease, which occurs 4-5 times more frequently than in the general population. Hemorrhagic presentations are usually mild, with gum bleeding and easy bruising; however, serious GI hemorrhage can occur. Forty percent of patients experience life-altering pruritus. Typically, the pruritus is worse after a warm shower or bath; this is known as aquagenic pruritus. It has been attributed to increased numbers of mast cells and elevated histamine levels.

Next

Physical

Potential physical findings include plethora and ruddiness of the face, erythromelalgia of the distal extremities, bruising, and splenomegaly. Specific attention should be directed towards sternal tenderness, which may indicate transformation to acute myeloid leukemia.[12]

Previous
Next

Causes

See Pathophysiology.

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Josef T Prchal, MD  Professor, Department of Medicine, Division of Hematology, Adjunct Professor of Pathology and Genetics, University of Utah School of Medicine

Josef T Prchal, MD, is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Human Genetics, Association of American Physicians, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Coauthor(s)

Scott J Samuelson, MD  Fellow in Hematology and Oncology, Huntsman Cancer Institute, University of Utah School of Medicine

Scott J Samuelson, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Sharada A Sarnaik, MBBS  Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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 School of Medicine; 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.

Helen SI Chan, MBBS, FRCP(C), FAAP  Associate Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto Faculty of Medicine, Canada

Helen SI Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References

  1. Ismael O, Shimada A, Hama A, Sakaguchi H, Doisaki S, Muramatsu H, et al. Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children. Pediatr Blood Cancer. Nov 21 2011;[Medline].

  2. 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].

  3. Nussenzveig RH, Swierczek SI, Jelinek J, et al. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol. Jan 2007;35(1):32-8. [Medline].

  4. Vannucchi AM, Antoniolim E, Guglielmelli P, et al. Plenary session. ASH Annual Meeting Abstracts. Blood. 2006;108.

  5. Silver RT. Interferon alfa: effects of long-term treatment for polycythemia vera. Semin Hematol. Jan 1997;34(1):40-50. [Medline].

  6. Silver RT. Recombinant interferon-alpha for treatment of polycythaemia vera. Lancet. Aug 13 1988;2(8607):403. [Medline].

  7. Carobbio A, Finazzi G, Antonioli E, et al. JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol. Sep 2009;37(9):1016-21. [Medline].

  8. Berk PD, Wasserman LR, Fruchtman SM. Treatment of polycythemia vera: a summary of clinical trials conducted by the polycythemia vera study group. In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia vera and the myeloproliferate disorders. Philadelphia: WB Saunders; 1995:166.

  9. Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. Apr 1 2005;23(10):2224-32. [Medline].

  10. Patel RK, Lea NC, Heneghan MA, Westwood NB, Milojkovic D, Thanigaikumar M. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. Jun 2006;130(7):2031-8. [Medline].

  11. Thurmes PJ, Steensma DP. Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis. Eur J Haematol. Jul 2006;77(1):57-60. [Medline].

  12. Giona F, Teofili L, Moleti ML, Martini M, Palumbo G, Amendola A, et al. Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome. Blood. Mar 8 2012;119(10):2219-27. [Medline].

  13. [Guideline] 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].

  14. Kondo T, Okuno N, Naruse H, et al. Validation of the revised 2008 WHO diagnostic criteria in 75 suspected cases of myeloproliferative neoplasm. Leuk Lymphoma. Sep 2008;49(9):1784-91. [Medline].

  15. Di Nisio M, Barbui T, Di Gennaro L, et al. The haematocrit and platelet target in polycythemia vera. Br J Haematol. Jan 2007;136(2):249-59. [Medline].

  16. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. Jan 8 2004;350(2):114-24. [Medline].

  17. Kiladjian JJ, Cassinat B, Turlure P, et al. High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. Blood. Sep 15 2006;108(6):2037-40. [Medline].

  18. Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L. Polycythemia vera: stem-cell and probable clonal origin of the disease. N Engl J Med. Oct 21 1976;295(17):913-6. [Medline].

  19. Ang SO, Prchal JT. The polycythemia vera and other polycythemic disorders: biological aspects. In: Melo JV, Goldman JM, eds. Myeloproliferative Diseases. New York, NY: Springer-Verlag; 2006:297-319.

  20. Finazzi G, Barbui T. How I treat patients with polycythemia vera. Blood. Jun 15 2007;109(12):5104-11. [Medline].

  21. Fisher MJ, Prchal JF, Prchal JT, D'Andrea AD. Anti-erythropoietin (EPO) receptor monoclonal antibodies distinguish EPO-dependent and EPO-independent erythroid progenitors in polycythemia vera. Blood. Sep 15 1994;84(6):1982-91. [Medline].

  22. Fruchtman SM, Mack K, Kaplan ME, Peterson P, Berk PD, Wasserman LR. From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. Jan 1997;34(1):17-23. [Medline].

  23. Hino M, Futami E, Okuno S, Miki T, Nishizawa Y, Morii H. Possible selective effects of interferon alpha-2b on a malignant clone in a case of polycythemia vera. Ann Hematol. Mar 1993;66(3):161-2. [Medline].

  24. Hoffman R, Prchal JT, Samuelson S, Ciurea SO, Rondelli D. Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment. Biol Blood Marrow Transplant. Jan 2007;13(1 Suppl 1):64-72. [Medline].

  25. Kralovics R, Guan Y, Prchal JT. Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera. Exp Hematol. Mar 2002;30(3):229-36. [Medline].

  26. 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].

  27. Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. Mar 15 2007;109(6):2446-52. [Medline].

  28. Liu E, Jelinek J, Pastore YD, Guan Y, Prchal JF, Prchal JT. Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin. Blood. Apr 15 2003;101(8):3294-301. [Medline].

  29. Messora C, Bensi L, Vecchi A, et al. Cytogenetic conversion in a case of polycythaemia vera treated with interferon-alpha. Br J Haematol. Feb 1994;86(2):402-4. [Medline].

  30. Prchal JF, Axelrad AA. Letter: Bone-marrow responses in polycythemia vera. N Engl J Med. Jun 13 1974;290(24):1382. [Medline].

  31. Prchal JT, Beutler E. Primary and secondary polycythemias (erythrocytosis). In: Lichtman MA, Beutler E, Kaushansky K, Kipps TJ, Seligsohn U, Prchal JT, eds. Williams Hematology. New York: McGraw-Hill; 2005.

  32. Tefferi A, Thiele J, Orazi A, et al. 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].

  33. Ugo V, James C, Vainchenker W. [A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera]. Med Sci (Paris). Jun-Jul 2005;21(6-7):669-70. [Medline].

  34. Ugo V, Marzac C, Teyssandier I, et al. Multiple signaling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia vera. Exp Hematol. Feb 2004;32(2):179-87. [Medline].

 
Previous
Next
 
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.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
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.