Main Article Content
carotid Doppler, thalasssemia, iron overload, atherosclerosis.
Iron over- load in patients with beta-thalassemia major lead to alterations in the arterial structures and in the thickness of the carotid arteries. Doppler ultrasound scanning of extra-cranial internal carotid arteries is non-invasive and fairly quick to perform and may identify children at increased risk of stroke who would otherwise be missed. Increased carotid artery intima media thickness (cIMT) is a structural marker for early atherosclerosis and it correlates with the vascular risk factors and to the severity and extent of coronary artery disease.
Objective: To evaluate the role of carotid Doppler examination and cIMT measurement as a predictive to atherosclerotic changes in BTM children with iron overload.
Patients and Methods: Sixty two children with (BTM) and 30 healthy normal controls of matched age and sex were included. Complete blood count, serum iron, ferritin, serum cholesterol and hemoglobin electrophoresis were performed as well as carotid Doppler ultrasonography to measure the (cIMT) in both patients and controls. Results: By using carotid Doppler we found that cIMT of thalassemic patients was significantly increased compared to normal controls and there was significant positive correlation between CIMT and patient's age, weight, height, BMI, duration of illness, serum cholesterol, iron overload parameters as serum iron, serum ferritin, frequent blood transfusion, irregular use of iron chelating agents and in those who had splenectomy. Significant negative correlation was found between CIMT and hematocrit value but no significant correlation was found between CIMT and Hb level. Conclusion: Carotid Doppler is very useful method in measurement of cIMT that increased in thalassemic patients which shows a strong relationship with features of iron overload. We recommend the routine use of Doppler measurement of cIMT in these patients to predict early atherosclerotic changes as well as in the follow-up to prevent progression of atherosclerosis.
2- Tuzmen S, Schechter AN. Genetic diseases of hemoglobin: diagnostic methods for elucidating beta-thalassemia mutations. Blood Rev 15: 19–29, 2001
3- Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias.Nat Rev Genet 2: 245–255, 2001
4- Hoffman R. Hematology: Basic Principles and Practice. New York: Churchill-Livingstone, 2005
5- Ekatherina Stoyanova , Marie Trudel , Hady Felfly , Damien Garcia , Guy Cloutier.Characterization of circulatory disorders in ?-thalassemic mice by noninvasive ultrasound biomicroscopy :Physiological Genomics Published 1 March 2007Vol. 29no. 1,84
6- FrancescaVinchi1, Martina U. Muckenthaler, Milene C. DaSilva, György Balla, József Balla and ViktóriaJen. "Atherogenesis and iron: from epidemiology to cellular level. Published: 05May2014 doi: 10.3389/fphar.2014.0009
7- 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 thalassaemia major treated with transfusion and deferoxamine". Haematologica 2004, 89:1187-93.
8- Colin R. Deane, David Goss, Jack Bartram, Keith R.E. Pohl, Susan E. Height, Naomi Sibtain, Jozef Jarosz, Swee Lay Thein, and David C. Rees Extracranial internal carotid arterial disease in children with sickle cell anemia: Haematologica. Aug 2010; 95(8): 1287–1292.Published online Mar 10, 2010. doi: 10.3324/haematol.2010.022624
9- - Aggoun Y, Szezepanski I, Bonnet D. Non invasive assessment of arterial stiffness and risk of atherosclerotic events in children. Pediatr Res. 2005;58(2):173-8.
10- Järvisalo MJ, Raitakari M, Toikka JO, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type-1 diabetes. Circulation.2004; 109(14):1750-5.
11- Cheung YF. Arterial Stiffness in Children and Teenagers: An Emerging Cardiovascular Risk Factor. HK J Paediatr, 2005;10:299-306.
12- Cooley TB, Lee P: "A series of cases of splenomegaly in children with anemia and peculiar changes". Trans Am Pediatr Soc 1925, 37:29-30.
13- Aessopos A, Farmakis D, Tsironi M, et al. Endothelial function and arterial stiffness in sickle-thalassemia patients. Atherosclerosis. 2007;191(2):427-32.
14- Cheung YF, Chow PC, Chan GC, Ha SY. Carotid intima-media thickness is increased and related to arterial stiffening in patients with b-thalassaemia major. Br J Haematol. 2006;135(5):732-4.
15- Tantawy A.G Azza, Adly A.M Amira, El Maaty G.A Mohamed and Amin A.G. Shatha. Subclinical Atherosclerosis In Young ?-thalassemia Major Patients. Hemoglobin. 2009; 33(6):463-74.
16- Gullu H, Caliskan M, Caliskan Z, Unler GK, Ermisler E, Ciftci O, Guven A, Muderrisoglu H. "Coronary Microvascular function, Peripheral Endothelial Function and Carotid IMT in beta-thalassemia minor"Thromb Res.2013 Jun;131(6):e247-52. doi: 10.1016/j.thromres.2013.03.013. Epub 2013 May 15.
17- Adly AA, El-Sherif NH, Ismail EA, El-Zaher YA, Farouk A, El-Refaey AM, Wahba MS."Vascular Dysfunction in Patients With Young ?-Thalassemia: Relation to Cardiovascular Complications and Subclinical Atherosclerosis". Clin Appl Thromb Hemost. 2014 Jul 2. pii: 1076029614541515. [Epub ahead of print]
18- Csmà Piccione M1, Piraino B, Zito C, Khandheria BK, Di Bella G, De Gregorio C, Oreto L, Rigoli L, Ferraù V, Salpietro CD, Carerj S.."Early identification of cardiovascular involvement in patients with ?-thalassemia major" Am J Cardiol 2013 Oct 15;112(8):1246-51. doi: 10.1016/j.amjcard.2013.05.080. Epub 2013 Jul 19.
19- Stoyanova E, Trudel M, Felfly H, Lemsaddek W, Garcia D, et al. Vascular Endothelial Dysfunction in b -Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO. PLoS 2012 ONE 7(6): e38089. doi:10.1371/journal.pone.0038089.
20- Gursel O1, Kurekci AE, Tascilar E, Ileri T, Altun D, Tapan S, Kurt I, Kocaoglu M, Aydin A, Okutan V, Ozcan O. Premature Atherosclerosis in Children With ?-Thalassemia Major" Journal of Pediatric Hematology/Oncology 2012; 34(8):630-4.
21- McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, Dickson R, Dundar Y, Greenhalgh J, Modell B, et al.: Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation. Health Technol Assess 2009, 13(1):iii-iv.ix-xi, 1-121.
22- Christoforidis A, Haritandi A, Tsitouridis I, Tsatra I, Tsantali H, Karyda S,Dimitriadis AS, Athanassiou-Metaxa M: Correlative study of iron accumulation in liver, myocardium, and pituitary assessed with MRI inyoung thalassemic patients. J Pediatr Hematol Oncol 2006, 28(5):311-5.
23- Papanikolaou G, Pantopoulos K: Iron metabolism and toxicity. Toxicol Appl Pharmacol 2005, 202(2):199-211.
24- Qayyum R, Schulman P: Iron and atherosclerosis. Clin Cardiol 2005, 28(3):119-22.
25- Shah SV, Alam MG: Role of iron in atherosclerosis. Am J Kidney Dis 2003, 41(3 Suppl 1):S80-83.
26- Cheung YF, Chan GC, Ha SY. Arterial stiffness and endothelial function in patients with beta-thalassemia major. Circulation 2002; 106:2561-6.
27- Ramakrishna G, Rooke TW, Cooper LT: Iron and peripheral arterial disease: revisiting the iron hypothesis in a different light. Vasc Med 2003, 8(3):203-10.
28- Ferrara DE, Taylor WR: Iron chelation and vascular function: in search of the mechanisms. Arterioscler Thromb Vasc Biol 2005, 25(11):2235-7.
29- Drueke T, Witko-Sarsat V, Massy Z, Descamps-Latscha B, Guerin AP, Marchais SJ, Gausson V, London GM: Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 2002, 106(17):2212-7.
30- Gaenzer H, Marschang P, Sturm W, Neumayr G, Vogel W, Patsch J, Weiss G: Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol2002, 40(12):2189-94.
31- de Valk B, Marx JJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med. 1999; 159(14):1542–8. doi: 10.1001/archinte.159.14.1542.
32- Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med.1989;320(14):915–924. doi: 10.1056/NEJM198904063201407.
33-Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57(5 Suppl):715S–724S. Discussion 724S-725S.
34- Hébert PC, McDonald BJ, Tinmouth . AClinical consequences of anemia and red cell transfusion in the critically ill. Crit Care Clin. 2004 Apr;20(2):225-35.
35- Jani SM, Smith DE, Share D, Kline-Rogers E, Khanal S, O'Donnell MJ, Gardin J, Moscucci M. Blood transfusion and in-hospital outcomes in anemic patients with myocardial infarction undergoing percutaneous coronary intervention. Clin Cardiol. 2007 Oct;30(10 Suppl 2):II49-56.
36- Kim P, Dixon S, Eisenbrey AB, O'Malley B, Boura J, O'Neill W. Impact of acute blood loss anemia and red blood cell transfusion on mortality after percutaneous coronary intervention. Clin Cardiol. 2007 Oct;30(10 Suppl 2):II35-43.