Abstract：This article summarizes the pathogenesis of hypercoagulability in β thalassemia patients, including platelet activation, alteration of red blood cell membranes, abnormal expression of adhesion molecules on vascular endothelial cells and iron overload. Clinical evidence, clinical manifestations of hypercoagulable state and thrombosis in β thalassemia and the effect of splenectomy on hypercoagulable state were reviewed. Strategies to prevent and treat the thromboembolic events in β-thalassemia intermedia are also discussed, including transfusion therapy to raise hemoglobin levels, avoidance or delay of splenectomy and a number of treatments in the exploration.
LV Rong-Yu,WEN Fei-Qiu,YU Jie. Advances in pathogenesis and correlated clinical research of hypercoagulability in β thalassemia[J]. CJCP, 2014, 16(7): 774-778.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators[J]. Bull World Health Organ, 2008, 86(6): 480-487.
[2]
Eldor A, Lellouche F, Goldfarb A, et al. In vivo platelet activation in β-thalassemia major reflected by increased plateletthromboxane urinary metabolites[J]. Blood, 1991, 77(8): 749-753.
[3]
Del Principe D, Menichelli A, Di Giulio S, et al. PADGEM/GMP-140 expression on platelet membranes from homozygous beta thalassaemic patients[J]. Br J Haematol, 1993, 84(1): 111-117.
[4]
Goldschmidt N, Spectre G, Brill A, et al. Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells[J]. Thromb Haemost, 2008, 100(5): 864-870.
[5]
Mannu F, Arese P, Cappellini MD, et al. Role of hemichrome binding to erythrocyte membrane in the generation of band-3 alterations in beta-thalassemia intermedia erythrocytes[J]. Blood, 1995, 86(5): 2014-2020.
[6]
Cappellini MD, Tavazzi D, Duca L, et al. Metabolic indicators of oxidative stress correlate with haemichrome attachment to membrane, band 3 aggregation and erythrophagocytosis in betathalassaemia intermedia[J]. Br J Haematol, 1999, 104(3): 504-512.
[7]
Rivella S. The role of ineffective erythropoiesis in nontransfusion-dependent thalassemia[J]. Blood Rev, 2012(Suppl 1): S12-S15.
[8]
Tan X, Shi J, Fu Y, et al. Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation[J]. Thromb Haemost, 2013, 109(6): 1025-1032.
[9]
Zwaal RF, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells[J]. Blood, 1997, 89(4): 1121-1132.
[10]
Hovav T, Goldfarb A, Artmann G, et al. Enhanced adherence of beta-thalassaemic erythrocytes to endothelial cells[J]. Br J Haematol, 1999, 106(1): 178-181.
Aleman MM, Gardiner C, Harrison P, et al. Differential contributions of monocyte-and platelet-derived microparticles towards thrombin generation and fibrin formation and stability[J]. J Thromb Haemost, 2011, 9(11): 2251-2261.
[13]
Habib A, Kunzelmann C, Shamseddeen W, et al. Elevated levels of circulating procoagulant microparticles in patients with β-thalassemia intermedia[J]. Haematologica, 2008, 93(6): 941-942.
[14]
Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia[J]. Ann N Y Acad Sci, 2010, 1202: 205-213.
[15]
Elgammal M, Mourad Z, Sadek N, et al. Plasma levels of soluble endothelial protein C-receptor in patients with β-thalassemia[J]. Alex J Med, 2012, 48: 283-288.
[16]
Taher A, Hershko C, Cappellini MD. Iron overload in thalassaemia intermedia:reassessment of iron chelation strategies[J]. Br J Haematol, 2009, 147(5): 634-640.
[17]
Gardenghi S, Grady RW, Rivella S. Anemia,ineffective erythropoiesis, and hepcidin: interacting factors in abnormal iron metabolism leading to iron overload in beta-thalassemia[J]. Hematol Oncol Clin North Am, 2010, 24(6): 1089-1107.
[18]
Teli A, Economou M, Rudolf J, et al. Subclinical central nervous system involvement and thrombophilic status in young thalassemia intermedia patients of Greek origin[J]. Blood Coagul Fibrinolysis, 2012, 23(3): 195-202.
[19]
Borgna Pignatti C, Carnelli V, Caruso V, et al. Thromboembolic events in beta thalassemia major:an Italian multicenter study[J]. Acta Haematol, 1998, 99(2): 76-79.
[20]
Taher A, Isma'eel H, Mehio G, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran[J]. Thromb Haemost, 2006, 96(4): 488-491.
[21]
Musallam KM, Beydoun A, Hourani R, et al. Brain magnetic resonance angiography in splenectomized adults with betathalassemia intermedia[J]. Eur J Haematol, 2011, 87(6): 539-546.
[22]
Musallam KM, Taher AT, Karimi M, et al. Cerebral infarction in beta-thalassemia intermedia: Breaking the silence[J]. Thromb Res, 2012, 130(5): 695-670.
[23]
Taher AT, Musallam KM, Nasreddine W, et al. Asymptomatic brain magnetic resonance imaging abnormalities in splenectomized adults with thalassemia intermedia[J]. J Thromb Haemost, 2010, 8(1): 54-59.
[24]
Taher AT, Musallam KM, Karimi M, et al. Splenectomy and thrombosis: the case of thalassemia intermedia[J]. J Thromb Haemost, 2010, 8(10): 2152-2158.
[25]
Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study[J]. Blood, 2010, 115(10): 1886-1892.
[26]
Akhlaghpoor S, Ghahari A, Morteza A, et al. Quantitative T2 Magnetic Resonance Imaging for Evaluation of Iron Deposition in the Brain of β-Thalassemia Patients[J]. Clin Neuroradiol, 2012, 22(3): 211-217.
[27]
Musallam KM, Cappellini MD, Wood JC, et al. Elevated liver iron concentration is a marker of increased morbidity in patients with βthalassemia intermedia[J]. Haematologica, 2011, 96(11): 1605-1612.
[28]
Karimi M, Bagheri H, Rastgu F, et al. Magnetic resonance imaging to determine the incidence of brain ischaemia in patients with beta-thalassaemia intermedia[J]. Thromb Haemost, 2010, 103: 989-993.
[29]
Cappellini MD, Robbiolo L, Bottasso BM, et al. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia[J]. Br J Haematol, 2000, 111(2): 467-473.
[30]
Musallam KM, Taher AT, Cappellini MD, et al. Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia[J]. Blood, 2013, 121(12): 2199-2212.
[31]
Ansari SH, Shamsi TS, Ashraf M, et al. Efficacy of Hydroxyurea in Providing Transfusion Independence in β-Thalassemia[J]. J Pediatr Hematol Oncol, 2011, 33(5): 339-343.
[32]
Sankaran VG, Xu J, Ragoczy T, et al. Developmental and species-divergent globin switching are driven by BCL11A[J]. Nature, 2009, 460(7259): 1093-1097.
[33]
Singer ST, Vichinsky EP, Sweeters N, et al. Darbepoetin alfa for the treatment of anaemia in alpha-or beta-thalassaemia intermedia syndromes[J]. Br J Haematol, 2011, 154(2): 281-284.
[34]
Elalfy MS, Adly AA, Ismail EA, et al. Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin overhydroxyurea in young β-thalassemia intermedia patients[J]. Eur J Haematol, 2013, 91(6): 522-533.
[35]
Preza GC, Ruchala P, Pinon R, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload[J]. J Clin Invest, 2011, 121(12): 4880-4888.
[36]
Li H, Rybicki AC, Suzuka SM, et al. Transferrin therapy ameliorates disease in beta-thalassemic mice[J]. Nat Med, 2010, 16(2): 177-182.
