Blood Reviews
Volume 22, Issue 5 , Pages 283-292 , September 2008

Thalassemia and hypercoagulability

  • Ali T. Taher

      Affiliations

    • Hematology-Oncology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
    • Corresponding Author InformationCorresponding author. Tel.: +961 3 755669; fax: +961 1 370814.
    • ,
  • Zaher K. Otrock

      Affiliations

    • Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
    • ,
  • Imad Uthman

      Affiliations

    • Rheumatology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
    • ,
  • Maria D. Cappellini

      Affiliations

    • Centro Anemie Congenite, University of Milan, Milano, Italy

References 

  1. Olivieri NF. The beta-thalassemias. N Engl J Med. 1999;341:99–109
  2. Camaschella C, Cappellini MD. Thalassemia intermedia. Haematologica. 1995;80:58–68
  3. Michaeli J, Mittelman M, Grisaru D, Rachmilewitz EA. Thromboembolic complications in beta thalassemia major. Acta Haematol. 1992;87:71–74
  4. Aessopos A, Farmakis D, Karagiorga M, Rombos I, Loucopoulos D. Pseudoxanthoma elasticum lesions and cardiac complications as contributing factors for strokes in beta-thalassemia patients. Stroke. 1997;28:2421–2424
  5. Moratelli S, De Sanctis V, Gemmati D, Serino ML, Mari R, Gamberini MR, et al. Thrombotic risk in thalassemic patients. J Pediatr Endocrinol Metab. 1998;11(Suppl. 3):915–921
  6. Borgna Pignatti C, Carnelli V, Caruso V, Dore F, De Mattia D, Di Palma A, et al. Thromboembolic events in beta thalassemia major: an Italian multicenter study. Acta Haematol. 1998;99:76–79
  7. Akar N, Kemahli S, Uysal Z, Cin S. Thromboembolism in beta-thalassemia major. Acta Haematol. 1998;100:166
  8. Senanayake MP, Lamabadusuriya SP. Cerebral thrombosis in beta-thalassaemia major. Indian J Pediatr. 2001;68:1081–1082
  9. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000;111:467–473
  10. Zalloua PA, Shbaklo H, Mourad YA, Koussa S, Taher A. Incidence of thromboembolic events in Lebanese thalassemia intermedia patients. Thromb Haemost. 2003;89:767–768
  11. Taher A, Isma’eel H, Mehio G, Bignamini D, Kattamis A, Rachmilewitz EA, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96:488–491
  12. 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. AJR Am J Roentgenol. 1999;173:1477–1480
  13. Zurlo MG, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, et al. Survival and causes of death in thalassaemia major. Lancet. 1989;2:27–30
  14. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187–1193
  15. Gillis S, Cappellini MD, Goldfarb A, Ciceri L, Fiorelli G, Rachmilewitz EA. Pulmonary thromboembolism in thalassemia intermedia patients. Haematologica. 1999;84:959–960
  16. van Teunenbroek A, Wijburg FA, ten Cate JW, van den Berg W, Weening RS. Thromboembolic complications in an asplenic HbE-beta-thalassaemia patient. Neth J Med. 1989;35:123–127
  17. Sonakul D, Pacharee P, Laohapand T, Fucharoen S, Wasi P. Pulmonary artery obstruction in thalassaemia. Southeast Asian J Trop Med Public Health. 1980;11:516–523
  18. Sumiyoshi A, Thakerngpol K, Sonakul D. Pulmonary microthromboemboli in thalassemic cases. Southeast Asian J Trop Med Public Health. 1992;23(Suppl. 2):29–31
  19. Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood. 2002;99:36–43
  20. Winichagoon P, Fucharoen S, Wasi P. Increased circulating platelet aggregates in thalassaemia. Southeast Asian J Trop Med Public Health. 1981;12:556–560
  21. Del Principe D, Menichelli A, Di Giulio S, De Matteis W, Cianciulli P, Papa G. PADGEM/GMP-140 expression on platelet membranes from homozygous beta thalassaemic patients. Br J Haematol. 1993;84:111–117
  22. Ruf A, Pick M, Deutsch V, Patscheke H, Goldfarb A, Rachmilewitz EA, et al. In-vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with beta-thalassaemia major. Br J Haematol. 1997;98:51–56
  23. Eldor A, Krausz Y, Atlan H, Snyder D, Goldfarb A, Hy-Am E, et al. Platelet survival in patients with beta-thalassemia. Am J Hematol. 1989;32:94–99
  24. 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
  25. 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
  26. Rund D, Rachmilewitz E. Beta-thalassemia. New Engl J Med. 2005;353:1135–1146
  27. Shinar E, Rachmilewitz EA, Lux SE. Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia. J Clin Invest. 1989;83:404–410
  28. Hershko C, Graham G, Bates GW, Rachmilewitz EA. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol. 1978;40:255–263
  29. Kuypers FA, de Jong K. The role of phosphatidylserine in recognition and removal of erythrocytes. Cell Mol Biol (Noisy-le-grand). 2004;50:147–158
  30. Tavazzi D, Duca L, Graziadei G, Comino A, Fiorelli G, Cappellini MD. Membrane-bound iron contributes to oxidative damage of beta-thalassaemia intermedia erythrocytes. Br J Haematol. 2001;112:48–50
  31. 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
  32. 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 beta-thalassemia. Thromb Haemost. 1996;76:322–327
  33. Atichartakarn V, Angchaisuksiri P, Aryurachai K, Onpun S, Chuncharunee S, Thakkinstian A, et al. Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/beta-thalassaemic patients. Br J Haematol. 2002;118:893–898
  34. Chen S, Eldor A, Barshtein G, Zhang S, Goldfarb A, Rachmilewitz E, et al. Enhanced aggregability of red blood cells of beta-thalassemia major patients. Am J Physiol. 1996;270:H1951–H1956
  35. Butthep P, Bunyaratvej A, Funahara Y, Kitaguchi H, Fucharoen S, Sato S, et al. Alterations in vascular endothelial cell-related plasma proteins in thalassaemic patients and their correlation with clinical symptoms. Thromb Haemost. 1995;74:1045–1049
  36. Butthep P, Bunyaratvej A, Funahara Y, Kitaguchi H, Fucharoen S, Sato S, et al. Possible evidence of endothelial cell activation and disturbance in thalassemia: an in vitro study. Southeast Asian J Trop Med Public Health. 1997;28(Suppl. 3):141A–148A
  37. Hovav T, Goldfarb A, Artmann G, Yedgar S, Barshtein G. Enhanced adherence of beta-thalassaemic erythrocytes to endothelial cells. Br J Haematol. 1999;106:178–181
  38. Butthep P, Rummavas S, Wisedpanichkij R, Jindadamrongwech S, Fucharoen S, Bunyaratvej A. Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia. Am J Hematol. 2002;70:100–106
  39. Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood. 1994;84:2068–2101
  40. Mann KG, van’t Veer C, Cawthern K, Butenas S. The role of the tissue factor pathway in initiation of coagulation. Blood Coagul Fibrinolysis. 1998;9(Suppl. 1):S3–S7
  41. Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM. Membrane microparticles: two sides of the coin. Physiology (Bethesda). 2005;20:22–27
  42. Pattanapanyasat K, Noulsri E, Fucharoen S, Lerdwana S, Lamchiagdhase P, Siritanaratkul N, et al. Flow cytometric quantitation of red blood cell vesicles in thalassemia. Cytometry B Clin Cytom. 2004;57:23–31
  43. Habib A, Kunzelmann C, Shamseddeen W, Isma’eel H, Zobairi F, Freyssinet J et al. Circulating microparticles in lebanese patients with beta-thalassemia intermedia. In: ASH; 2006: Blood; 2006. p. 1589.
  44. Pattanapanyasat K, Gonwong S, Chaichompoo P, Noulsri E, Lerdwana S, Sukapirom K, et al. Activated platelet-derived microparticles in thalassaemia. Br J Haematol. 2007;136:462–471
  45. Wiener E, Wanachiwanawin W, Chinprasertsuk S, Siripanyaphinyo U, Mawas F, Fucharoen S, et al. Increased serum levels of macrophage colony-stimulating factor (M-CSF) in alpha- and beta-thalassaemia syndromes: correlation with anaemia and monocyte activation. Eur J Haematol. 1996;57:364–369
  46. Deo SS, Merchant SM, Kapadia AC. Elevated polymorphonuclear phagocytic function in thalassemia patients by chemiluminescence. Indian J Pediatr. 1994;61:395–399
  47. Kivity S, Gazy C, Heno N, Greif Z, Topilsky M. Effect of the Leukostop filter on pulmonary function following blood transfusion in patients with thalassemia major. Pediatr Pulmonol. 1999;28:277–281
  48. Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann N Y Acad Sci. 2005;1054:317–324
  49. Atichartakarn V, Angchaisuksiri P, Aryurachai K, Chuncharunee S, Thakkinstian A. In vivo platelet activation and hyperaggregation in hemoglobin E/beta-thalassemia: a consequence of splenectomy. Int J Hematol. 2003;77:299–303
  50. Tripatara A, Jetsrisuparb A, Teeratakulpisarn J, Kuaha K. Hemostatic alterations in splenectomized and non-splenectomized patients with beta-thalassemia/hemoglobin E disease. Thromb Res. 2007;120:805–810
  51. Iolascon A, Giordano P, Storelli S, Li HH, Coppola B, Piga A, et al. Thrombophilia in thalassemia major patients: analysis of genetic predisposing factors. Haematologica. 2001;86:1112–1113
  52. Shirahata A, Funahara Y, Opartkiattikul N, Fucharoen S, Laosombat V, Yamada K. Protein C and protein S deficiency in thalassemic patients. Southeast Asian J Trop Med Public Health. 1992;23(Suppl. 2):65–73
  53. Visudhiphan S, Ketsa-Ard K, Tumliang S, Piankijagum A. Significance of blood coagulation and platelet profiles in relation to pulmonary thrombosis in beta-thalassemia/Hb E. Southeast Asian J Trop Med Public Health. 1994;25:449–456
  54. Musumeci S, Leonardi S, Di Dio R, Fischer A, Di Costa G. Protein C and antithrombin III in polytransfused thalassemic patients. Acta Haematol. 1987;77:30–33
  55. Giordano P, Galli M, Del Vecchio GC, Altomare M, Norbis F, Ruggeri L, et al. Lupus anticoagulant, anticardiolipin antibodies and hepatitis C virus infection in thalassaemia. Br J Haematol. 1998;102:903–906
  56. Sharma S, Raina V, Chandra J, Narayan S. Lupus anticoagulant and anticardiolipin antibodies in polytransfused beta thalassemia major. Hematology. 2006;11:287–290
  57. Kashef S, Karimi M, Amirghofran Z, Ayatollahi M, Pasalar M, Ghaedian MM, et al. Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patients. Int J Lab Hematol. 2008;30:11–16
  58. Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J Am Coll Cardiol. 1999;33:1424–1426
  59. Tiosano D, Hochberg Z. Endocrine complications of thalassemia. J Endocrinol Invest. 2001;24:716–723
  60. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007;21:37–47
  61. Morris CR, Kuypers FA, Kato GJ, Lavrisha L, Larkin S, Singer T, et al. Hemolysis-associated pulmonary hypertension in thalassemia. Ann NY Acad Sci. 2005;1054:481–485
  62. Eldor A, Durst R, Hy-Am E, Goldfarb A, Gillis S, Rachmilewitz EA, et al. A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood. Br J Haematol. 1999;107:739–746

PII: S0268-960X(08)00036-2

doi: 10.1016/j.blre.2008.04.001

Blood Reviews
Volume 22, Issue 5 , Pages 283-292 , September 2008

Article Tools

* Image Usage & Resolution