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The Effect of Antiplatelet Autoantibodies on Megakaryocytopoiesis

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Abstract

Immune thrombocytopenic purpura (ITP) is a disorder manifested by isolated thrombocytopenia. In vivo infusion studies in the 1950s and 1960s provided evidence that the thrombocytopenia was due to autoantibody-induced platelet destruction. However, there is mounting evidence that platelet production in this disorder may also be suppressed by antibodies. Early morphologic studies showed megakaryocytic damage in ITP, and these results have been confirmed by ultrastructural studies. Autologous platelet turnover studies in the 1980s showed that most ITP patients have either normal or reduced platelet turnover rather than increased turnover, as would be expected if platelet destruction were the only pathogenetic mechanism. More recently, in vitro culture studies of both adult and pediatric ITP have shown that some ITP plasmas suppress both megakaryocytopoiesis and thrombopoiesis. In view of these findings, both platelet destruction and suppression of platelet production seem likely to be involved in the pathogenesis of ITP.

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References

  1. Frank E. Die essentielle Thrombopenie. (Konstitutionelle Purpura- Pseudohämophilie), I: Klinische Bild. Berl Klin Wochenschr. 1915;52:454–458.

    Google Scholar 

  2. Kaznelson P. Verschwinden der hämorrhagischen Diathese bei einem Falle von “essentieller Thrombopenie” (Frank) nach Milzexstirpation: Splenogene thrombolytische Purpura. Wien Klin Wochenschr. 1916;29:1451–1454.

    Google Scholar 

  3. Harrington WJ, Sprague CC, Minnich V, Moore CV, Aulvin RC, Dubach R. Immunologic mechanisms in idiopathic and neonatal thrombocytopenic purpura. Ann Intern Med. 1953;38:433–469.

    Article  PubMed  CAS  Google Scholar 

  4. Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura: physiologic, serologic, and isotopic studies. Ann N Y Acad Sci. 1965;124:499–542.

    Article  PubMed  CAS  Google Scholar 

  5. McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol. 2000;37:239–248.

    Article  PubMed  CAS  Google Scholar 

  6. Firkin BG, Wright R, Miller S, Stokes E. Splenic macrophages in thrombocytopenia. Blood. 1969;33:240–245.

    PubMed  CAS  Google Scholar 

  7. McMillan R, Longmire RL, Tavassoli M, Armstrong S, Yelenosky R. In vitro platelet phagocytosis by ITP splenic leukocytes in idiopathic thrombocytopenic purpura. N Engl J Med. 1974;290:249–251.

    Article  PubMed  CAS  Google Scholar 

  8. Tsubakio T, Kurata Y, Kanayama Y, Yonezawa T, Tarui S, Kitani T. In vitro platelet phagocytosis in idiopathic thrombocytopenic purpura. Acta Haematol. 1983;70:250–256.

    Article  PubMed  CAS  Google Scholar 

  9. Hauch TW, Rosse WF. Platelet-bound complement (C3) in immune thrombocytopenia. Blood. 1977;50:1129–1136.

    PubMed  CAS  Google Scholar 

  10. Tsubakio T, Tani P, Curd JG, McMillan R. Complement activation in vitro by antiplatelet antibodies in chronic immune thrombocytopenic purpura. Br J Haematol. 1986;63:293–300.

    Article  PubMed  CAS  Google Scholar 

  11. Vainchenker W, Deschamps JF, Bastin JM, et al. Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in in vivo cells from normal and leukemic patients. Blood. 1982;59:514–521.

    PubMed  CAS  Google Scholar 

  12. McKenna JL, Pisciotta AV. Fluorescence of megakaryocytes in idiopathic thrombocytopenic purpura (ITP) stained with fluorescent antiglobulin serum. Blood. 1962;19:664–674.

    Google Scholar 

  13. Joshi BC, Jain NC. Detection of antiplatelet antibody in serum and on megakaryocytes of dogs with autoimmune thrombocytopenia. Am J Vet Res. 1976;37:681–685.

    PubMed  CAS  Google Scholar 

  14. McMillan R, Luiken GA, Levy R, Yelenosky R, Longmire RL. Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA. 1978;239:2460–2462.

    Article  CAS  PubMed  Google Scholar 

  15. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood. 1946;1:27–52.

    CAS  PubMed  Google Scholar 

  16. Diggs LW, Hewlett JS. A study of the bone marrow from thirty-six patients with idiopathic hemorrhagic (thrombopenic) purpura. Blood. 1948;3:1090–1104.

    CAS  PubMed  Google Scholar 

  17. Pisciotta AV, Stefanini M, Dameshek W. Studies on platelets, X: morphologic characteristics of megakaryocytes by phase contrast microscopy in normals and in patients with idiopathic thrombocytopenic purpura. Blood. 1953;8:703–723.

    CAS  PubMed  Google Scholar 

  18. Stahl CP, Zucker-Franklin D, McDonald TP. Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP. Blood. 1986;67:421–428.

    CAS  PubMed  Google Scholar 

  19. Houwerzijl EJ, Blom NR, van der Want JJL, et al. Ultrastructural study shows morphological features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500–506.

    Article  CAS  PubMed  Google Scholar 

  20. Heyns AP, Lotter MG, Badenhorst PN, et al. Kinetics and sites of destruction of 111Indium-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study. Am J Hematol. 1982;12:167–177.

    Article  PubMed  CAS  Google Scholar 

  21. Stoll D, Cines DB, Aster RH, Murphy S. Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. Blood. 1985;65:584–588.

    PubMed  CAS  Google Scholar 

  22. Heyns AP, Badenhorst PN, Lotter MG, Pieters H, Wessels P, Kotze HF. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled and homologous 51Cr-labeled platelets differ. Blood. 1986;67:86–92.

    Google Scholar 

  23. Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter S. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura: evidence for both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80:33–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Bellucci S, Han ZC, Caen JP. Studies of in vitro megakaryocytopoiesis in adult immune thrombocytopenic purpura (ITP). Eur J Haematol. 1991;47:86–90.

    Article  PubMed  CAS  Google Scholar 

  25. Abgrall J, Berthou C, Sensebe L, Le Niger C, Escoffre M. Decreased in vitro megakaryocyte colony formation in chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1993;85:803–804.

    Article  PubMed  CAS  Google Scholar 

  26. Hoffman R, Mazur E, Bruno E, Floyd V. Assay of an activity in the serum of patients with disorders of thrombopoiesis that stimulates formation of megakaryocytic colonies. N Engl J Med. 1981;305:533–538.

    Article  PubMed  CAS  Google Scholar 

  27. Chang M, Nakagawa PA, Williams SA, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 2003;102:887–895.

    Article  PubMed  CAS  Google Scholar 

  28. Takahashi R, Sekine N, Nakatake T. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood. 1999;93:1951–1958.

    PubMed  CAS  Google Scholar 

  29. Zauli G, Catani L, Gibellini D, et al. Impaired survival of bone marrow GPIIb/IIa+ megakaryocytic cells as an additional pathogenetic mechanism of HIV-1-related thrombocytopenia. Br J Haematol. 1996;92:711–717.

    Article  PubMed  CAS  Google Scholar 

  30. Zauli G, Vitale M, Falcieri E, et al. In vitro senescence and apoptotic cell death of human megakaryocytes. Blood. 1997;90:2234–2243.

    PubMed  CAS  Google Scholar 

  31. McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult chronic ITP patients. Blood. 2004;103:1364–1369.

    Article  PubMed  CAS  Google Scholar 

  32. Nugent DJ, Kunicki TJ. Autoimmune thrombocytopenic purpura. In: Theofilopoulos A, Bona C, eds. The Molecular Pathology of Autoimmune Diseases. New York, NY: Taylor & Francis; 2002:543–566.

    Google Scholar 

  33. Mattia G, Vulcano F, Milazzo L, et al. Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release. Blood. 2002;99:888–897.

    Article  PubMed  CAS  Google Scholar 

  34. Olsson B, Andersson P, Jernas M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123–1124.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Robert McMillan.

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McMillan, R., Nugent, D. The Effect of Antiplatelet Autoantibodies on Megakaryocytopoiesis. Int J Hematol 81, 94–99 (2005). https://doi.org/10.1532/IJH97.04168

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  • DOI: https://doi.org/10.1532/IJH97.04168

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