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. 2002;113:68–77.

Thrombocytosis: too much of a good thing?

Andrew I Schafer 1
PMCID: PMC2194473  PMID: 12053719

Abstract

Thrombocytosis is due to (a) a variety of disorders that cause reactive stimulation of platelet production, (b) familial mutations, or (c) essential thrombocythemia (ET) and other myeloproliferative disorders (MPDs). The MPDs are clonal abnormalities of the pluripotent hematopoietic stem cell. Dysregulation of megakaryocytopoiesis in ET involves defective binding of thrombopoietin by platelets and megakaryocytes resulting in increased levels of plasma free thrombopoietin, and increased sensitivity of megakaryocytes to thrombopoietin leading to their increased proliferation. Bleeding and thrombosis are the major causes of morbidity and mortality in ET and the other MPDs. The elevated platelet count and qualitative platelet defects have been implicated in the pathophysiology of these hemostatic problems. However, these platelet abnormalities do not correlate well with clinical complications. It is proposed that bleeding and thrombosis could be due to vascular abnormalities that result from dysfunctional hematopoietic stem cell-derived endothelial cells.

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Selected References

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  1. Aviram A., Blickstein D., Stark P., Luboshitz J., Bairey O., Prokocimer M., Shaklai M. Significance of BCR-ABL transcripts in bone marrow aspirates of Philadelphia-negative essential thrombocythemia patients. Leuk Lymphoma. 1999 Mar;33(1-2):77–82. doi: 10.3109/10428199909093727. [DOI] [PubMed] [Google Scholar]
  2. Axelrad A. A., Eskinazi D., Correa P. N., Amato D. Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia. Blood. 2000 Nov 15;96(10):3310–3321. [PubMed] [Google Scholar]
  3. Bazzan M., Tamponi G., Schinco P., Vaccarino A., Foli C., Gallone G., Pileri A. Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia. Ann Hematol. 1999 Dec;78(12):539–543. doi: 10.1007/s002770050555. [DOI] [PubMed] [Google Scholar]
  4. Buss D. H., Cashell A. W., O'Connor M. L., Richards F., 2nd, Case L. D. Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med. 1994 Mar;96(3):247–253. doi: 10.1016/0002-9343(94)90150-3. [DOI] [PubMed] [Google Scholar]
  5. Carmeliet P., Luttun A. The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis. Thromb Haemost. 2001 Jul;86(1):289–297. [PubMed] [Google Scholar]
  6. Cortelazzo S., Finazzi G., Ruggeri M., Vestri O., Galli M., Rodeghiero F., Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132–1136. doi: 10.1056/NEJM199504273321704. [DOI] [PubMed] [Google Scholar]
  7. Emilia G., Marasca R., Zucchini P., Temperani P., Luppi M., Torelli G., Lanza F., De Angelis C., Gandini D., Castoldi G. L. BCR-ABL rearrangement is not detectable in essential thrombocythemia. Blood. 2001 Apr 1;97(7):2187–2189. doi: 10.1182/blood.v97.7.2187. [DOI] [PubMed] [Google Scholar]
  8. Falanga A., Marchetti M., Evangelista V., Vignoli A., Licini M., Balicco M., Manarini S., Finazzi G., Cerletti C., Barbui T. Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera. Blood. 2000 Dec 15;96(13):4261–4266. [PubMed] [Google Scholar]
  9. Fialkow P. J., Faguet G. B., Jacobson R. J., Vaidya K., Murphy S. Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. Blood. 1981 Nov;58(5):916–919. [PubMed] [Google Scholar]
  10. Goodell M. A., Jackson K. A., Majka S. M., Mi T., Wang H., Pocius J., Hartley C. J., Majesky M. W., Entman M. L., Michael L. H. Stem cell plasticity in muscle and bone marrow. Ann N Y Acad Sci. 2001 Jun;938:208–220. doi: 10.1111/j.1749-6632.2001.tb03591.x. [DOI] [PubMed] [Google Scholar]
  11. Harrison C. N., Gale R. E., Machin S. J., Linch D. C. 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 Jan 15;93(2):417–424. [PubMed] [Google Scholar]
  12. Horikawa Y., Matsumura I., Hashimoto K., Shiraga M., Kosugi S., Tadokoro S., Kato T., Miyazaki H., Tomiyama Y., Kurata Y. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia. Blood. 1997 Nov 15;90(10):4031–4038. [PubMed] [Google Scholar]
  13. Hou M., Andersson P. O., Stockelberg D., Mellqvist U. H., Ridell B., Wadenvik H. Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes. Br J Haematol. 1998 Jun;101(3):420–424. doi: 10.1046/j.1365-2141.1998.00747.x. [DOI] [PubMed] [Google Scholar]
  14. Ikpeazu C., Davidson M. K., Halteman D., Browning P. J., Brandt S. J. Donor origin of circulating endothelial progenitors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2000;6(3A):301–308. doi: 10.1016/s1083-8791(00)70055-3. [DOI] [PubMed] [Google Scholar]
  15. Jackson K. A., Majka S. M., Wang H., Pocius J., Hartley C. J., Majesky M. W., Entman M. L., Michael L. H., Hirschi K. K., Goodell M. A. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001 Jun;107(11):1395–1402. doi: 10.1172/JCI12150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Masuda H., Kalka C., Asahara T. Endothelial progenitor cells for regeneration. Hum Cell. 2000 Dec;13(4):153–160. [PubMed] [Google Scholar]
  17. Nimer S. D. Essential thrombocythemia: another "heterogeneous disease" better understood? Blood. 1999 Jan 15;93(2):415–416. [PubMed] [Google Scholar]
  18. Pitcher L., Taylor K., Nichol J., Selsi D., Rodwell R., Marty J., Taylor D., Wright S., Moore D., Kelly C. Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia. Br J Haematol. 1997 Dec;99(4):929–932. doi: 10.1046/j.1365-2141.1997.4633267.x. [DOI] [PubMed] [Google Scholar]
  19. Ravandi-Kashani F., Schafer A. I. Microvascular disturbances, thrombosis, and bleeding in thrombocythemia: current concepts and perspectives. Semin Thromb Hemost. 1997;23(5):479–488. doi: 10.1055/s-2007-996125. [DOI] [PubMed] [Google Scholar]
  20. Reisner S. A., Rinkevich D., Markiewicz W., Tatarsky I., Brenner B. Cardiac involvement in patients with myeloproliferative disorders. Am J Med. 1992 Nov;93(5):498–504. doi: 10.1016/0002-9343(92)90576-w. [DOI] [PubMed] [Google Scholar]
  21. Schafer A. I. Bleeding and thrombosis in the myeloproliferative disorders. Blood. 1984 Jul;64(1):1–12. [PubMed] [Google Scholar]
  22. Tefferi A., Fonseca R., Pereira D. L., Hoagland H. C. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. 2001 Jan;76(1):22–28. doi: 10.4065/76.1.22. [DOI] [PubMed] [Google Scholar]
  23. Wang J. C., Chen C., Novetsky A. D., Lichter S. M., Ahmed F., Friedberg N. M. Blood thrombopoietin levels in clonal thrombocytosis and reactive thrombocytosis. Am J Med. 1998 May;104(5):451–455. doi: 10.1016/s0002-9343(98)00090-4. [DOI] [PubMed] [Google Scholar]
  24. Wiestner A., Padosch S. A., Ghilardi N., Cesar J. M., Odriozola J., Shapiro A., Skoda R. C. Hereditary thrombocythaemia is a genetically heterogeneous disorder: exclusion of TPO and MPL in two families with hereditary thrombocythaemia. Br J Haematol. 2000 Jul;110(1):104–109. doi: 10.1046/j.1365-2141.2000.02169.x. [DOI] [PubMed] [Google Scholar]

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