Introduction: Patients with thalassemia major often present with a hypercoagulable state, the pathogenesis of which is still not understood. Materials and Methods: This study evaluates the risk factors for hypercoagulability in 50 β-thalassemia major patients and 50 healthy controls. Fasting total homocysteine, protein C (PC), protein S (PS), antithrombin (AT), activated protein C resistance (APCR) and lupus anticoagulant (LA) were assessed. MTHFR C677T mutation was determined. Results: Significant reductions in PC, PS and AT were noted in patients. Only 4% of the patients had hyperhomocysteinemia. Thirty-two percent of the patients were heterozygous and 4% were homozygous for MTHFR C677T mutation. Conclusion: The natural coagulation inhibitors PC, PS and AT were significantly reduced in patients with β-thalassemia major and were thus important risk factors for the hypercoagulable state, but hyperhomocysteinemia and MTHFR mutation do not seem to be significant risk factors for thromboembolic events.

Keywords:
β-Thalassemia major, Hypercoagulable state, Kuwait, Methylenetetrahydrofolate reductase (MTHFR) C677T mutation
1.
Harrison CR: Hemolytic anemias: intracorpuscular defect. IV. Thalassemia; in Harmening DM (ed): Clinical Hematology and Fundamentals of Hemostasis, ed 4. Philadelphia, Davis, 2002, pp 186–199.
2.
Olivieri NF: The β-thalassemias. N Engl J Med 1999;341:99–109.
3.
Adekile AD, Gu LH, Baysal E, Haider MZ, al-Fuzae L, Aboolbacker KC, al-Rashied A, Huisman THJ: Molecular characterization of α-thalassemia determinants, β-thalassemia alleles, and βS haplotypes among Kuwaiti Arabs. Acta Haematol 1994;92:176–181.
4.
al-Fuzae L, Aboolbacker CK, al-Saleh Q: β-Thalassemia major in Kuwait. J Trop Pediatr 1998;44:311–312.
5.
Cunningham MJ, Macklin EA, Nenfeld EJ, Cohen AR: Complications of β-thalassemia major in North America. Blood 2004;104:34–39.
6.
Hoffbrand AV, Pettit JE, Moss PAH: Genetic disorders of haemoglobin; in Essential Haematology, ed 4. Oxford, Blackwell, 2002, pp 71–90.
7.
Barrano B, Bertrand G, Lsaja T, Curreri R, Musumeci S: Plasma homocysteine is not involved in the thrombotic risk of β-thalassemia major patients. Acta Haematol 2000;104:148–150.
8.
Eldor A, Rachmilewitz EA: The hypercoagulable state in thalassemia. Blood 2002;99:36–43.
9.
Michaeli J, Mittelman M, Grisaru D, Rachmilewitz EA: Thromboembolic complications in beta thalassemia major. Acta Haematol 1992;87:71–74.
10.
Moratelli S, De Sanctis V, Gemmati D, Serino ML, Mari R, Gamberini MR, Scapoli GL: Thrombotic risk in thalassemic patients. J Pediatr Endocrinol Metab 1998;11:915–921.
11.
Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A: Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004;89:1187–1193.
12.
Eldor A, Durst R, Hy-Am E, Goldfarb A, Gillis S, Rachmilewitz EA, Abramov A, Maclouf J, Godefray YC, de Raucourt E, Guillin MC: A chronic hypercoagulable state in patients with β-thalassemia major is already present in childhood. Br J Haematol 1999;107:739–746.
13.
Giordano P, Sabato V, Schettini F, De Mattia D, Iolascon A: Resistance to activated protein C as a risk factor of stroke in a thalassemic patient. Haematologica 1997;82:698–700.
14.
Giordano P, Del Vecchio GC, Altomare M, Coppola B, Schettini F, Lolascon A, De Maffia D: Resistance to activated protein C in thalassemic patients: an underlying cause of thrombosis. Eur J Haematol 1998;61:123–127.
15.
Dahlbäck B, Carlsson M, Svensson PJ: Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993;90:1004–1008.
16.
Kassab-Chekir A, Laradi S, Ferchichi S, Khelil AH, Feki M, Amri F, Selmi H, Bejaoui M, Miled A: Oxidant, antioxidant status and metabolic data in patients with beta-thalassemia. Clin Chim Acta 2003;338:79–86.
17.
Mojtahedzadeh F, Kosaryan M, Mahdavi MR, Akbari J: The effect of folic acid supplementation in beta thalassemia major: a randomized placebo controlled clinical trial. Arch Iran Med 2006;9:266–268.
18.
Kosaryan M, Mahdavi MR, Shahmoradi M, Arabzadeh M: Is it necessary to give folic acid to thalassemia minor or major? International Congress on Pediatrics, Tehran, 2003.
19.
Rahimi Z, Ghaderi M, Nagel RL, Muniz A: Prevalence of thrombotic risk factors among β-thalassemia patients from Western Iran. J Thromb Thrombolysis 2008;26:229–233.
20.
Chaloupecky V, Svobodova I, Hadacova I, Tomek V, Huín B, Tláskal T, Janoušek J, Reich O, Škovránek J: Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up. Heart 2005;91:73–79.
21.
Sipahi T, Kara A, Kuybulu A, Egin Y, Akar N: Congenital thrombotic risk factors in beta-thalassemia. Clin Appl Thromb Hemost 2008, E-pub ahead of print. doi:10.1177/1076029608316170.
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2009
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