Review
A clinical update in polycythemia vera and essential thrombocythemia

https://doi.org/10.1016/S0002-9343(00)00449-6Get rights and content

Abstract

Polycythemia vera and essential thrombocythemia pose specific management issues that distinguish them from other chronic myeloproliferative disorders. They are associated with a better prognosis, as well as a variable risk of thrombohemorrhagic complications. In addition, essential thrombocythemia occurs comparatively more often in young people and women. Treatment strategies for patients with polycythemia vera and essential thrombocythemia must consider the possibility of long-term survival, morbidity from thrombotic complications, transformation into myelofibrosis with myeloid metaplasia or acute myeloid leukemia, and the effect of specific therapies on the incidence of leukemic transformation and on pregnancy. There is increasing concern about the possible leukemogenic effect of hydroxyurea. Newer therapeutic agents, including interferon alpha and anagrelide, are being used more often. Ongoing studies are reexamining the effects of low-dose aspirin in preventing thrombotic complications.

Section snippets

Pathogenesis

Several studies have shown that the clonal process in polycythemia vera originates in stem cells (5). The underlying molecular lesion has not been identified. Recent studies have focused on the mechanisms responsible for the proliferation and survival of red blood cells independent of erythropoietin (6). Structural or functional alterations of the erythropoietin receptor or its corresponding downstream effectors have not been detected 7, 8. The erythropoietin-independent viability of red blood

Pathogenesis

X-linked enzyme or genetic analysis has suggested that patients with essential thrombocythemia have clonal hematopoiesis that originates in stem cells 31, 32. However, the issue of clonality is complicated by the recent demonstration of monoclonal hematopoiesis in normal elderly women (33) and polyclonal hematopoiesis in some patients with essential thrombocythemia (34).

It is not certain if there is a pathogenetic link between clonal thrombocytosis and thrombopoietin. In patients with essential

Is hydroxyurea leukemogenic?

Polycythemia vera and essential thrombocythemia are clonal disorders with an inherent tendency to evolve into acute myeloid leukemia 3, 53. Because they are not genetically defined, biologic heterogeneity could exist within each disease group, and this may affect the risk of developing leukemia. In addition, longer duration of disease and evolution into myelofibrosis increase the risk of leukemic transformation 3, 54. Therefore, patient selection may influence observed rates of leukemic

Conclusion

Treatment strategies for patients with polycythemia vera or essential thrombocythemia are based primarily on the presence or absence of risk factors for thrombohemorrhagic complications Table 4, Table 5, Table 6. Treatment may require modification in women who are, or plan to become, pregnant.

Low-risk patients may fare better without any cytoreductive therapy 3, 47, and the use of low-dose aspirin in these patients is optional 28, 81. Although there is no good evidence that drug therapy

References (97)

  • N el-Kassar et al.

    Clonality analysis of hematopoiesis in essential thrombocythemiaadvantages of studying T lymphocytes and platelets

    Blood

    (1997)
  • C.N Harrison et al.

    A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications

    Blood

    (1999)
  • J.C Wang et al.

    Blood thrombopoietin levels in clonal thrombocytosis and reactive thrombocytosis

    Am J Med

    (1998)
  • Y Horikawa et al.

    Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia

    Blood

    (1997)
  • A.L Taksin et al.

    Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L

    Blood

    (1999)
  • A Tefferi et al.

    Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis

    Am J Med

    (1994)
  • Y Najean et al.

    Treatment of polycythemia verause of 32P alone or in combination with maintenance therapy using hydroxyurea in 461 patients greater than 65 years of age

    Blood

    (1997)
  • Y Najean et al.

    Treatment of polycythemia verathe use of hydroxyurea and pipobroman in 292 patients under the age of 65 years

    Blood

    (1997)
  • Y Sterkers et al.

    Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyureahigh proportion of cases with 17p deletion

    Blood

    (1998)
  • E.M Mazur et al.

    Analysis of the mechanism of anagrelide-induced thrombocytopenia in humans

    Blood

    (1992)
  • R.T Silver

    Recombinant interferon-alpha for treatment of polycythaemia vera

    Lancet

    (1988)
  • R Delage et al.

    Treatment of essential thrombocythemia during pregnancy with interferon-alpha

    Obstet Gynecol

    (1996)
  • U Ebert et al.

    Cytotoxic therapy and pregnancy

    Pharmacol Ther

    (1997)
  • R Landolfi et al.

    Increased thromboxane biosynthesis in patients with polycythemia veraevidence for aspirin-suppressible platelet activation in vivo

    Blood

    (1992)
  • U Budde et al.

    Acquired von Willebrand’s disease in the myeloproliferative syndrome

    Blood

    (1984)
  • M.S Daoud et al.

    Hydroxyurea dermopathya unique lichenoid eruption complicating long-term therapy with hydroxyurea

    J Am Acad Dermatol

    (1997)
  • C Rozman et al.

    Life expectancy of patients with chronic nonleukemia myeloproliferative disorders

    Cancer

    (1991)
  • Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD. Treatment of polycythemia vera: a summary of clinical trials...
  • S Cortelazzo et al.

    Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis

    N Engl J Med

    (1995)
  • W.H Raskind et al.

    Clonal development of myeloproliferative disordersclues to hematopoietic differentiation and multistep pathogenesis of cancer

    Leukemia

    (1998)
  • G Hess et al.

    Molecular analysis of the erythropoietin receptor system in patients with polycythaemia vera

    Br J Haematol

    (1994)
  • F.A Asimakopoulos et al.

    The gene encoding hematopoietic cell phosphatase (SHP-1) is structurally and transcriptionally intact in polycythemia vera

    Oncogene

    (1997)
  • M Silva et al.

    Expression of Bcl-x in erythroid precursors from patients with polycythemia vera

    N Engl J Med

    (1998)
  • A.R Moliterno et al.

    Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera

    N Engl J Med

    (1998)
  • N.I Berlin

    Diagnosis and classification of the polycythemias

    Semin Hematol

    (1975)
  • G Birgegard et al.

    Serum erythropoietin in the diagnosis of polycythaemia and after phlebotomy treatment

    Br J Haematol

    (1992)
  • P.M Cotes et al.

    Determination of serum immunoreactive erythropoietin in the investigation of erythrocytosis

    N Engl J Med

    (1986)
  • N.B Westwood et al.

    Diagnostic applications of haemopoietic progenitor culture techniques in polycythaemias and thrombocythaemias

    Leuk Lymphoma

    (1996)
  • Tefferi A, Yoon SY, Li CY. Immunohistochemical staining for megakaryocyte c-Mpl may complement morphologic distinction...
  • B.J Ania et al.

    Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935–1989

    Am J Hematol

    (1994)
  • R.A Mesa et al.

    Population-based incidence, and survival figures in essential thrombocythemia, and agnogenic myeloid metaplasia. an Olmsted County study, 1976–1995

    Am J Hematol

    (1999)
  • Polycythemia verathe natural history of 1213 patients followed for 20 years

    Ann Intern Med

    (1995)
  • G.E Brown et al.

    Peripheral arterial disease in polycythemia vera

    Arch Intern Med

    (1930)
  • Y Najean et al.

    Risk of leukaemia, carcinoma, and myelofibrosis in 32P- or chemotherapy-treated patients with polycythaemia veraa prospective analysis of 682 cases. The French Cooperative Group for the Study of Polycythaemias

    Leuk Lymphoma

    (1996)
  • S.M Fruchtman et al.

    From efficacy to safetya Polycythemia Vera Study Group report on hydroxyurea in patients with polycythemia vera

    Semin Hematol

    (1997)
  • Low-dose aspirin in polycythaemia veraa pilot study

    Br J Haematol

    (1997)
  • T.C Pearson et al.

    The course and complications of idiopathic erythrocytosis

    Clin Lab Haematol

    (1979)
  • K.M Champion et al.

    Clonal haemopoiesis in normal elderly womenimplications for the myeloproliferative disorders and myelodysplastic syndromes

    Br J Haematol

    (1997)
  • Cited by (105)

    • The JAK2 mutation

      2021, International Review of Cell and Molecular Biology
      Citation Excerpt :

      Essential thrombocythemia (ET), previously described as “hemorrhagic thrombocythemia”, is characterized by the proliferation of megakaryocytes in bone marrow and thrombocytosis in peripheral blood without association with erythrocytosis and leucoerythroblastosis. Megakaryocytes feature hyperlobated nuclei, and megakaryocyte precursors are hypersensitive to several cytokines, including thrombopoietin, IL-3, and IL-6 (Li et al., 1994; Tefferi et al., 2000). ET can occur as a clonally heterogeneous disease, and sometimes clonality is only restricted to megakaryocytic lineage (el Kassar et al., 1995; Harrison et al., 1999).

    • Thrombocytosis: Essential Thrombocythemia and Reactive Causes

      2013, Consultative Hemostasis and Thrombosis: Third Edition
    • Thrombocytosis and Essential Thrombocythemia

      2012, Platelets, Third Edition
    • Chronic Myeloproliferative Disorders

      2010, Current Clinical Medicine: Expert Consult Premium Edition - Enhanced Online Features and Print
    View all citing articles on Scopus
    1

    Dr. Silverstein was involved in the initial preparation of this manuscript. He died on September 15, 1998.

    View full text