In vivo Platelet Activation and Hyperaggregation in Hemoglobin E/β-Thalassemia: A Consequence of Splenectomy


Patients with hemoglobin E/β-thalassemia (E/β-Thal) who have undergone splenectomy are prone to thrombosis in the small pulmonary arteries.To study the role of platelets in this situation, we assayed plasma β2-thromboglobulin (βTG) and performed whole blood platelet aggregation analysis of 30 E/β-Thal patients, half of whom had undergone splenectomy.We compared results with those obtained with 15 healthy control subjects. Plasma βTG levels in splenectomy patients were significantly higher than in control subjects and patients who had not undergone splenectomy, and platelets in splenectomy patients exhibited hyperaggregation in response to adenosine diphosphate, thrombin, and ristocetin. Levels of plasma thrombin-antithrombin III complex were also significantly higher. This finding is likely due to an increased number of erythrocytes with exposed phosphatidylserines, an effect that has been associated with splenectomy. The increased presence of thrombin in the blood may well be the cause of platelet hyperactivity, which was evident only in the asplenic patients. Platelet hyperactivity very likely plays a pathogenetic role in the thrombosis of small pulmonary arteries that occurs in E/β-Thal patients who have undergone splenectomy.

This is a preview of subscription content, log in to check access.


  1. 1.

    Sonakul D, Pacharee P, Laohapand T, Fucharoen S, Wasi P. Pulmonary artery obstruction in thalassemia.Southeast Asian J Trop Med Public Health. 1980;11:516–523.

    PubMed  CAS  Google Scholar 

  2. 2.

    Logothetis J, Constantoulakis M, Economidou J, et al. Thalassemia major (homozygous beta-thalassemia): a survey of 138 cases with emphasis on neurologic and muscular aspects.Neurology. 1972;22:294–3044.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Wong V, Yu YL, Liang RH, Tso WK, Li AM, Chan TK. Cerebral thrombosis in beta-thalassemia/hemoglobin E disease.Stroke. 1990;21:812–816.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Michaeli J, Mittelman M, Grisaru D, Rachmilewitz EA. Thromboembolic complications in beta thalassemia major.Acta Haematol. 1992;87:71–74.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Borgna-Pignatti C, Carnelli V, Caruso V, et al. Thromboembolic events in beta thalassemia major: an Italian multicenter study.Acta Haematol. 1998;99:76–79.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and disease complications in thalassemia major.Ann N Y Acad Sci. 1998;850:227–231.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Manfre L, Giarratano E, Maggio A, Banco A, Vaccaro G, Lagalla R. MR imaging of the brain: findings in asymptomatic patients with thalassemia intermedia and sickle cell-thalassemia disease.Am J Roentgenol. 1999;173:1477–1480.

    Article  CAS  Google Scholar 

  8. 8.

    Winichagoon P, Fucharoen S, Wasi P. Increased circulating platelet aggregates in thalassemia.Southeast Asian J Trop Med Public Health. 1981;12:556–560.

    PubMed  CAS  Google Scholar 

  9. 9.

    Eldor A, Lellouche F, Goldfarb A, Rachmilewitz EA, Maclouf J. In vivo platelet activation in beta thalassemia major reflected by increased platelet thromboxane urinary metabolites.Blood. 1991; 77:1749–1753.

    PubMed  CAS  Google Scholar 

  10. 10.

    Del-Principe D, Menichelli A, Di Giulio S, De Matteis W, Cianciulli P, Papa G. PADGEM/GMP-140 expression on platelet membrane from homozygous-thalassemia patients.Br J Haematol. 1993;84:111–1177.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Bunyaratvej A, Komanasin N, Sriurairatana S, Fucharoen S. Morphological assessment of platelet activation in thalassemia.Southeast Asian J Trop Med Public Health. 1992;23(suppl 2):60–64.

    PubMed  Google Scholar 

  12. 12.

    Opartkiattikul N, Funahara Y, Fucharoen S, Talalak P. Increase in spontaneous platelet aggregation in β-thalassemia/hemoglobin E disease: a consequence of splenectomy.Southeast Asian J Trop Med Public Health. 1992;23(suppl 2):36–41.

    PubMed  Google Scholar 

  13. 13.

    Eldor A. Abnormal platelet function in β-thalassaemia.Scand J Haematol. 1978;20:447–452.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Hussain MA, Hutton RA, Pavlidou O, Hoffbrand AV. Platelet function in beta thalassemia major.J Clin Pathol. 1979;32:429–433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Chantharaksri U, Tonsuwonnont W, Fucharoen S, Wasi P. Pathogenesis of hypoxemia.Southeast Asian J Trop Med Public Health. 1992;23(suppl 2):32–35.

    PubMed  Google Scholar 

  16. 16.

    Kaplan KL, Owen J. Plasma levels of 2-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo.Blood. 1981;57:199–202.

    PubMed  CAS  Google Scholar 

  17. 17.

    Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzymelinked immunosorbent assay.Thromb Haemost. 1988;59:101–106.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Kutlar A, Kutlar F, Wilson JB, Headlee MG, Huisman TH. Quantitation of hemoglobin components by high performance cationexchange liquid chromatography.Am J Hematol. 1984;17:39–53.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Forman DT, Parker SL. The measurement and interpretation of serum ferritin.Ann Clin Lab Sci. 1980;10:345–350.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. 20.

    Stata Corporation. Statistical Software: Release 6.0. College Station, Tex: Stata Corporation; 1999.

  21. 21.

    Ruf A, Pick M, Deutsch V, et al. In-vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with-thalassemia major.Br J Haematol. 1997;98:51–56.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Pareti EI, Capitanio A, Mannucci L, Ponticelli C, Mannucci PM. Acquired dysfunction due to the circulation of “exhausted” platelets.Am J Med. 1980;69:235–240.

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Angchaisuksiri P, Atichartakarn V, Aryurachai K, Onpun S, Chuncharunee S. Association of erythrocyte phosphatidylserine expression with activation of coagulation in patients with β-thalassemia/ Hb E disease.Blood. 1998;92(suppl 1):562a.

    Google Scholar 

  24. 24.

    Zwaal RFA, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells.Blood. 1997;89:1121–11322.

    PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    Borenstain-Ben Yashar V, Barenholz Y, Hy-Am E, Rachmilewitz EA, Eldor A. Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes.Am J Hematol. 1993;44:63–65.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Helley D, Eldor A, Girot R, Ducrocq R, Guillin MC, Bezeaud A. Increased procoagulant activity of red blood cells from patients with homozygous sickle-cell disease and -thalassemia.Thromb Haemost. 1996;76:322–327.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  27. 27.

    Peyrou V, Lormeau JC, Herault JP, Gaich C, Pfliegger AM, Herbert JM. Contribution of erythrocytes to thrombin generation in whole blood.Thromb Haemost. 1999;81:400–406.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci PM. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia.Br J Haematol. 2000;111:467–473.

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    FitzGerald G, Moran N. Molecular mechanisms of platelet activation and inhibition. In: Colman RW, Hirsh J, Marder VJ, Colwes AW, George JN, eds.Hemostasis and Thrombosis: Basic Principles & Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:1517–1527.

    Google Scholar 

  30. 30.

    Chuncharunee S, Hathirat P, Archararit N, Udomsubpayakul U, Atichartakarn V. Levels of serum interleukin-6 and tumor necrosis factor in postsplenectomized thalassemic patients.J Med Assoc Thai. 1997;80(suppl 1):86–91.

    Google Scholar 

  31. 31.

    Lumadue JA, Lanzkron SM, Kennedy SD, Kuhl DT, Kickler TS. Cytokine induction of platelet activation.Am J Clin Pathol. 1996; 106:795–798.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Peng J, Friese P, Wolf RF, et al. Relative reactivity of platelets from thrombopoietin-and interleukin-6-treated dogs.Blood. 1996;87:4158–41633.

    PubMed  CAS  Google Scholar 

  33. 33.

    Pasin M, Yavuzer S, Tekin M, Akar N, Violi F. Oxygen free radicaldependent increased platelet function in β-thalassemia major patients.Thromb Res. 1998;92:283–286.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Vichai Atichartakarn or Pantep Angchaisuksiri or Katcharin Aryurachai or Suporn Chuncharunee or Ammarin Thakkinstian.

About this article

Cite this article

Atichartakarn, V., Angchaisuksiri, P., Aryurachai, K. et al. In vivo Platelet Activation and Hyperaggregation in Hemoglobin E/β-Thalassemia: A Consequence of Splenectomy. Int J Hematol 77, 299–303 (2003).

Download citation

Key words

  • Platelet activation
  • β-Thalassemia
  • Splenectomy