eMedicine Specialties > Hematology > Stem Cells and Disorders

Thrombocytosis, Essential

Author: Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center
Contributor Information and Disclosures

Updated: Oct 4, 2009

Introduction

Background

Essential thrombocytosis (primary thrombocythemia), first described by Epstein and Goedel in 1934, is a nonreactive, chronic myeloproliferative disorder.1 Essential thrombocytosis (primary thrombocythemia) is associated with sustained megakaryocyte proliferation that increases the number of circulating platelets. Traditionally, essential thrombocytosis (primary thrombocythemia) was considered a clonal disorder that involved pluripotent stem cells; however, studies have indicated that some patients may have polyclonal hematopoiesis.

Essential thrombocytosis (primary thrombocythemia) is characterized by a platelet count greater than 600,000/µL, megakaryocytic hyperplasia, splenomegaly, and a clinical course complicated by thrombotic and/or hemorrhagic episodes.2,3,4,5,6,7,8,9,10,11,12

Peripheral blood smear in essential thrombocytosi...

Peripheral blood smear in essential thrombocytosis showing increased platelet numbers. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.

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Peripheral blood smear in essential thrombocytosi...

Peripheral blood smear in essential thrombocytosis showing increased platelet numbers. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.


Bone marrow biopsy in essential thrombocytosis s...

Bone marrow biopsy in essential thrombocytosis showing increased megakaryocytes. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.

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Bone marrow biopsy in essential thrombocytosis s...

Bone marrow biopsy in essential thrombocytosis showing increased megakaryocytes. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.


Pathophysiology

Platelet survival is normal in essential thrombocytosis (primary thrombocythemia). Megakaryocytes increase the production of platelets, causing thrombocytosis. The cause of this increase in platelet production remains unclear, though it may be a result of autonomous production, increased sensitivities to cytokines (eg, interleukin-3 [IL-3]), decreased inhibition to platelet-inhibiting factors (eg, transforming growth factor [TGF] beta), or defects in accessory cell microenvironment.

Bone marrow megakaryocytic precursors (colony-forming unit-megakaryocyte [CFU-Meg]) from patients with essential thrombocytosis (primary thrombocythemia) form colonies in the absence of exogenous thrombopoietin (Tpo). There is no evidence for mutations in the genes for c-Mpl or Tpo, and patients with essential thrombocytosis (primary thrombocythemia) have normal or even decreased plasma Tpo levels, possibly reflecting increased Tpo clearance due to the elevated circulating platelet mass. JAK2 mutations possibly turn receptor on permanently, but this could possibly occur even before the mutation becomes detectable as JAK-2 mutation is only seen in 50% of patients.

The mechanism by which thrombocythemia produces hemorrhage or thrombosis is not well defined. Several defects have been described, including a decrease in aggregation, hyperaggregation, and intracellular concentration of various chemicals. In addition, reports show a decrease in von Willebrand ristocetin cofactor activity and high molecular weight von Willebrand factor multimers. Some reports show patients with an acquired deficiency of antithrombin III, protein C, and protein S.6

Frequency

United States

Clinicians diagnose approximately 6000 cases of essential thrombocytosis (primary thrombocythemia) each year. Some researchers speculate that the incidence rate may be several times higher. A study from southeastern Minnesota reported an incidence of 2.38 cases per 100,000 population per year.13

Mortality/Morbidity

  • Patients with essential thrombocytosis (primary thrombocythemia) have a 10-year survival rate of 64-80%, which may not be significantly different from that of the age-matched general population. Death occurs from thrombotic complications. Transformation to acute myelogenous leukemia (AML) occurs in 0.6-5% of patients and may accelerate if the patient takes chemotherapeutic agents.
  • Patients with essential thrombocytosis (primary thrombocythemia) may experience symptoms relating to large vessel or microvascular thrombosis and bleeding.

Sex

In older patients with essential thrombocytosis (primary thrombocythemia), the frequency is similar in both sexes; however, essential thrombocytosis (primary thrombocythemia) occurs more often in young women than in young men.

Age

Essential thrombocytosis (primary thrombocythemia) is more frequent in older patients, although younger patients may develop the disease. The median age at diagnosis is 60 years, and perhaps up to 20% of patients are younger than 40 years. The disease is rare in children.

Clinical

History

Approximately 25-33% of patients with essential thrombocytosis (primary thrombocythemia) are asymptomatic at diagnosis. The remainder report vasomotor symptoms or complications from thrombosis or bleeding. Most symptomatic patients present with symptoms that relate to small- or large-vessel thrombosis. Some patients present with bleeding.

  • Neurologic symptoms
    • Headache is the most common neurologic symptom.
    • Microvascular occlusion of the toes and fingers causes digital pain, gangrene, or erythromelalgia. Erythromelalgia is characterized by burning pain and dusky extremity congestion.
    • The pain increases with exposure to heat and improves with cold; a single dose of aspirin may provide relief for several days.
    • Patients also report paresthesias and episodic transient ischemic attacks. Transient neurologic symptoms include the following:
      • Unsteadiness
      • Dysarthria
      • Dysphoria
      • Vertigo
      • Dizziness
      • Migraine
      • Syncope
      • Scotoma
      • Seizures
  • Thrombosis
    • Thrombosis of large veins and arteries is common and may result in occlusion of the leg, coronary, and renal arteries. Other arteries may be involved.
    • Venous thrombosis of the splenic, hepatic, or leg and pelvic veins may develop. Priapism is a rare complication. Pulmonary hypertension may result from pulmonary vasculature occlusion.
  • Bleeding
    • The gastrointestinal tract is the primary site of bleeding complications. Approximately 40% of the patients have duodenal arcade thrombosis, resulting in sloughing of the duodenal mucosa, simulating a duodenal ulcer.
    • Other sites of bleeding include the skin, eyes, gums, urinary tract, joints, and brain.
    • Bleeding is usually not severe and only rarely requires transfusion.
    • The bleeding is generally associated with a platelet count greater than 1 million/µL.
  • Constitutional symptoms (occur in 20-30% of patients). Weight loss is unusual. Other symptoms include sweating, low-grade fever, and pruritus.
  • Pregnancy complications14
    • Essential thrombocytosis (primary thrombocythemia) causes an increase in spontaneous abortions.
    • Placental infarctions may occur, resulting in intrauterine growth retardation and fetal death.
    • In most cases, fetal loss occurs during the first trimester.
    • A patient history of spontaneous abortion is the greatest risk factor for subsequent spontaneous abortions.
    • Excessive bleeding during delivery is rare.
    • Patients with successful pregnancies show a decrease in platelet count.

Physical

In most patients with essential thrombocytosis (primary thrombocythemia), physical examination findings are unremarkable. Approximately 40-50% of patients present with splenomegaly; 20% present with hepatomegaly.

Causes

The etiology and predisposing factors for the development of essential thrombocytosis (primary thrombocythemia) remain unclear. Genetic transmission of this disorder is rare, although reports show several families with multiple members affected by essential thrombocytosis (primary thrombocythemia). Research suggests that a thrombopoietin production or receptor abnormality can cause familial essential thrombocytosis (primary thrombocythemia).15

More on Thrombocytosis, Essential

Overview: Thrombocytosis, Essential
Differential Diagnoses & Workup: Thrombocytosis, Essential
Treatment & Medication: Thrombocytosis, Essential
Follow-up: Thrombocytosis, Essential
Multimedia: Thrombocytosis, Essential
References
Further Reading
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References

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  2. Barbui T, Finazzi G. Treatment indications and choice of a platelet-lowering agent in essential thrombocythemia. Curr Hematol Rep. May 2003;2(3):248-56. [Medline].

  3. Ruggeri M, Gisslinger H, Tosetto A, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. Sep 2002;71(1):1-6. [Medline]. [Full Text].

  4. Harrison CN, Donohoe S, Carr P, et al. Patients with essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis. Thromb Haemost. May 2002;87(5):802-7. [Medline].

  5. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. Apr 27 1995;332(17):1132-6. [Medline]. [Full Text].

  6. Bucalossi A, Marotta G, Bigazzi C, Galieni P, Dispensa E. Reduction of antithrombin III, protein C, and protein S levels and activated protein C resistance in polycythemia vera and essential thrombocythemia patients with thrombosis. Am J Hematol. May 1996;52(1):14-20. [Medline].

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  12. Kwon M, Osorio S, Muñoz C, Sánchez JM, Buno I, Díez-Martín JL. Essential thrombocythemia in patients with platelet counts below 600x10(9)/L: applicability of the 2008 World Health Organization diagnostic criteria revision proposal. Am J Hematol. Jul 2009;84(7):452-4. [Medline].

  13. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. May 1999;61(1):10-5. [Medline]. [Full Text].

  14. Tefferi A, Fonseca R, Pereira DL, Hoagland HC. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. Jan 2001;76(1):22-8. [Medline].

  15. Girodon F, Bonicelli G, Schaeffer C, Mounier M, Carillo S, Lafon I, et al. Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: a population-based study. Haematologica. Jun 2009;94(6):865-9. [Medline].

  16. Spanoudakis E, Margaritis D, Kotsianidis I, et al. Long-term bone marrow cultures (LTBMC) from essential thrombocythemia (ET) patients with or without JAK2617V>F mutation. Leuk Res. Oct 2008;32(10):1593-6. [Medline].

  17. Teofili L, Martini M, Cenci T, et al. Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases. Int J Cancer. Oct 1 2008;123(7):1586-92. [Medline].

  18. Ohyashiki K, Kodama A, Ohyashiki JH. Recurrent der(9;18) in essential thrombocythemia with JAK2 V617F is highly linked to myelofibrosis development. Cancer Genet Cytogenet. Oct 2008;186(1):6-11. [Medline].

  19. 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].

  20. Campbell PJ, Bareford D, Erber WN, Wilkins BS, Wright P, Buck G, et al. Reticulin accumulation in essential thrombocythemia: prognostic significance and relationship to therapy. J Clin Oncol. Jun 20 2009;27(18):2991-9. [Medline].

  21. [Best Evidence] Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. Jul 7 2005;353(1):33-45. [Medline]. [Full Text].

  22. Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. May 14 2009;113(20):4829-33. [Medline].

  23. Gugliotta L, Marchioli R, Fiacchini M, et al. Epidemiological, diagnostic, therapeutic and prognostic aspects of essential thrombocythemia in a retrospective study of the GIMMC group in two thousand patients [abstract]. Blood. 1997;90(suppl 1):348a.

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  28. el-Kassar N, Hetet G, Brière J, Grandchamp B. Clonality analysis of hematopoiesis in essential thrombocythemia: advantages of studying T lymphocytes and platelets. Blood. Jan 1 1997;89(1):128-34. [Medline]. [Full Text].

  29. Elliott MA, Tefferi A. Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 1997;23(5):463-72. [Medline].

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  31. Fabris F, Casonato A, Grazia del Ben M, De Marco L, Girolami A. Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. Br J Haematol. May 1986;63(1):75-83. [Medline].

  32. Harrison CN, Gale RE, Machin SJ, Linch DC. 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. Jan 15 1999;93(2):417-24. [Medline]. [Full Text].

  33. Jantunen R, Juvonen E, Ikkala E, et al. The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia. Ann Hematol. Feb 2001;80(2):74-8. [Medline].

  34. Kobayashi S, Teramura M, Hoshino S, et al. Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin-3. Br J Haematol. Apr 1993;83(4):539-44. [Medline].

  35. Randi ML, Barbone E, Zerbinati P, et al. Essential thrombocythemia following polycythemia vera: an unusual sequence. J Med. 1996;27(5-6):363-8. [Medline].

  36. Shabbad E, Cassel A, Froom P, Aghai E. Effect of adherent cells on the regulation of BFU-E in patients with myeloproliferative disease. Am J Hematol. Apr 1990;33(4):225-9. [Medline].

  37. van Genderen PJ, Michiels JJ, van der Poel-van de Luytgaarde SC, van Vliet HH. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: relationship with platelet count. Ann Hematol. Aug 1994;69(2):81-4. [Medline].

  38. Zauli G, Visani G, Catani L, et al. Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet-derived transforming growth factor beta 1, produced in normal amount, in patients with essential thrombocythaemia. Br J Haematol. Jan 1993;83(1):14-20. [Medline].

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Keywords

essential thrombocytosis, ET, thrombocytosis, thrombocythemia, high platelet count, primary thrombocythemia, idiopathic thrombocythemia, essential thrombocythemia, vascular thrombosis, acute myelogenous leukemia, AML, chronic myelogenous leukemia, CML, myeloproliferative disorders, polycythemia vera

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Contributor Information and Disclosures

Author

Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center
Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Wadie F Bahou, MD, Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook
Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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