Blood transfusion and iron overload in patients with Sickle Cell Disease (SCD): Personal experience and a short update of diabetes mellitus occurrence

Blood transfusion and iron overload in patients with Sickle Cell Disease (SCD): Personal experience and a short update of diabetes mellitus occurrence


  • Ashraf T Soliman
  • Vincenzo De Sanctis Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy
  • Mohamed Yassin Department of Hematology and Oncology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
  • Awni Alshurafa Department of Hematology and Oncology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
  • Fateen Ata Department of Hematology and Oncology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
  • Abdulqadir Nashwan Department of Hematology and Oncology, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar


Sickle cell disease, blood transfusion, iron overload, complications, glucose homeostasis, diabetes mellitus, metformin.


The conventional treatment of β-thalassemia (β-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with β-TM in comparison to those occurring in β-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (


Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet 2017;390:311–23.

Nader E, Conran N, Romana M, Connes P. Vasculopathy in Sickle Cell Disease: From Red Blood Cell Sickling to Vascular Dysfunction. Compr Physiol 2021;11:1785-803.

Nader E, Romana M, Connes P. The Red Blood Cell-Inflammation Vicious Circle in Sickle Cell Disease. Front Immunol. 2020;11:454.

Kassim AA, Sharma D. Hematopoietic stem cell transplantation for sickle cell disease: The changing landscape. Hematol Oncol Stem Cell Ther 2017;10:259-66.

Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. J Med 1995;332:1317–22.

Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA 2003;289:1645–51.

de Montalembert M, Voskaridou E, Oevermann L, et al.; All ESCORT HU Investigators. Real-Life experience with hydroxyurea in patients with sickle cell disease: Results from the prospective ESCORT-HU cohort study. Am J Hematol 2021 ;96: 1223-31.

Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312: 1033-48.

DeBaun MR. Hydroxyurea therapy contributes to infertility in adult men with sickle cell disease: a review. Expert Rev Hematol 2014;7:767-73.

Ballas SK. The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease. Mediterr J Hematol Infect Dis 2020;12(1):e2020010.

Rai P, Ataga KI. Drug Therapies for the Management of Sickle Cell Disease. F1000Res 2020;9:F1000 Faculty Rev-592.

Leibovitch JN, Tambe AV, Cimpeanu E, et al. l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope? Blood Rev 2022:100925.

Davis BA, Allard S, Qureshi A, et al. Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects. Br J Hematol 2017; 176:179–91.

Wang WC, Dwan K. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database Syst Rev 2013;11:003146.

Howard J. Sickle cell disease: when and how to transfuse. Hematol Am Soc Hematol Educ Program 2016;2016:625–31.

Inati A, Musallam KM, Wood JC, Taher AT. Iron overload indices rise linearly with transfusion rate in patients with sickle cell disease. Blood 2010;115:2980-1.

Inati A. Recent advances in improving the management of sickle cell disease. Blood Rev 2009; 23 (Suppl 1): S9-13.

Kwiatkowski JL, Hamdy M, El-Beshlawy A, et al. Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study. Blood Adv 2022; 6: 1243-54.

Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology Am Soc Hematol Educ Program 2013;447-56.

Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of Childhood and Adult Obesity in the United States, 2011-2012. JAMA 2014 311(8):806.

American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43 Suppl 1:S14–S31.

Taher AT, Porter J, Viprakasit V, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebocontrolled study. Blood 2012;120:970-7.

St Pierre TG, Clark PR, Chua-anusorn W. Single spin-echo proton transverse relaxometry of iron-loaded liver. NMR Biomed 2004; 17: 446–58.

Casale M, Meloni A, Filosa A, et al . Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study.Circ Cardiovasc Imaging 2015;8(8): e003230.

He T, Gatehouse PD, Smith GC, Mohiaddin RH, Pennell DJ, Firmin DN. Myocardial T2* measurements in iron-overloaded thalassemia: An in vivo study to investigate optimal methods of quantification. Magn Reson Med 2008;60:1082-9.

Koehl B, Missud F, Holvoet L, et al. Continuous manual exchange transfusion for patients with sickle cell disease: an efficient method to avoid iron overload. J Vis Exp 2017; 121:551-72.

Wood JC, GhugreN. Magnetic resonance imaging assessment of excess iron in thalassaemia, sickle cell disease and other iron overload diseases. Hemoglobin 2008;32:85–96.

Hogen R, Kim M, Lee Y, et al. Liver Transplantation in Patients with Sickle Cell Disease in the United States. J Surg Res 2020;255:23-32.

Oduor H, Minniti CP, Brofferio A, et al. Severe cardiac iron toxicity in two adults with sickle cell disease.Transfusion 2017;57:700–4.

Hankins JS, Smeltzer MP, McCarville MB, et al. Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload. Eur J Haematol 2010; 85:51–7.

Linder GE, Chao ST. Red cell transfusion and alloimmunization in sickle cell disease. Haematologica 2021;06:270546.

Abou Zahr R, Burkhardt BEU, Ehsan L, Potersnak A, Greil G, Dillenbeck J, et al. Real-world experience measurement of liver iron concentration by R2 vs. R2 Star MRI in hemoglobinopathies. Diagnostics 2020: 10:768.

Drasar E, Vasavda N, Igbineweka N, Awogbade M, Allman M, Thein SL. Serum ferritin and total units transfused for assessing iron overload in adults with sickle cell disease. Br J Haematol 2012;157:645-47.

Banerjee S, Owen C, Chopra S. Sickle cell hepatopathy. Hepatology 2001;33:1021-8.

Vichinsky E, Butensky E, Fung E, et al. Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia.Am J Hematol 2005; 80:70-4.

Shah R, Taborda C, Chawla S. Acute and chronic hepatobiliary manifestations of sickle cell disease: A review. World J Gastrointest Pathophysiol 2017;8:108-16.

Wood JC, Tyszka JM, Carson S, Nelson MD, Coates TD. Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease. Blood 2004;103:1934–6.

Meloni A, Puliyel M, Pepe A, Berdoukas V, Coates TD, Wood JC. Cardiac iron overload in sickle-cell disease. Am J Hematol 2014;89:678-83.

Bawor M, Kesse-Adu R, Gardner K, Marino P, Howard J, Webb J.Prevalence of cardiac abnormalities in sickle cell disease identified using cardiac magnetic resonance imaging, Eur Heart J 2020; 41 (Suppl. 2): ehaa946.1026.

Coates TD, Wood JC. How we manage iron overload in sickle cell patients. Br J Haematol 2017;177:703-16.

Alkindi S, Panjwani V, Al-Rahbi S, Al-Saidi K, Pathare AV. Iron Overload in Patients With Heavily Transfused Sickle Cell Disease-Correlation of Serum Ferritin With Cardiac T2* MRI (CMRTools), Liver T2* MRI, and R2-MRI (Ferriscan®). Front Med (Lausanne) 2021;8:731102.

Harrington JK, Krishnan U, Jin Z, Mardy C, Kobsa S, Lee MT. Longitudinal Analysis of Echocardiographic Abnormalities in Children With Sickle Cell Disease. J Pediatr Hematol Oncol 2017;39:500-5.

Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol 2012 59:1123-33.

Oduor H, Minniti CP, Brofferio A, et al. Severe cardiac iron toxicity in two adults with sickle cell disease. Transfusion. 2017;57:700-4.

Niss O, Fleck R, Makue F, et al. Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. Blood 2017;130:205-13.

Kaur H, Aurif F, Kittaneh M, Chio JPG, Malik BH. Cardiomyopathy in Sickle Cell Disease. Cureus 2020;12(8):e9619.

Darbari DS, Kple-Faget P, Kwagyan J, Rana S, Gordeuk VR, Castro O. Circumstances of death in adult sickle cell disease patients. Am J Hematol 2006;81:858–3.

Fung EB, Harmatz P, Milet M, et al; Multi-Center Study of Iron Overload Research Group. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol 2007;82:255-65.

Morrison JC, Schneider JM, Kraus AP, Kitabchi AE. The prevalence of diabetes mellitus in sickle cell hemoglobinopathies. J Clin Endocrinol Metab 1979;48:192-5.

Ngombe LK, Mulangu AM, Kasole TL, Numbi OL. Sickle cell disease and diabetes: a rare combination in a black teenager in Lubumbashi, Democratic Republic of Congo [in French]. Pan Afr Med J. 2014;18:74.

Abraham EC, Rao KR. Glycosylated hemoglobins in a diabetic patient with sickle cell anemia. Clin Physiol Biochem 1987;5:343-9.

Miodovnik M, Hurd WW, Lobel JS, Siddiqi TA. Pregnancy associated with both insulin-dependent diabetes mellitus and sickle cell disease. A report of two cases. J Reprod Med 1987; 32:317-9.

Reid HL, Photiades DP, Oli JM, Kaine W. Concurrent sickle cell disease and diabetes mellitus. Trop Geogr Med 1988;40:201-4.

Reid HL, Ene MD, Photiades DP, Famodu AA. Insulin-dependent diabetes mellitus in homozygous sickle-cell anaemia. Trop Geogr Med 1990;42:172-3.

Mohapatra MK. Type 1 diabetes mellitus in homozygous sickle cell anaemia. J Assoc Physicians India 2005;53:895-6.

Shoar Z, Rezvani G, De Luca F. Type 1 diabetes mellitus in a patient with homozygous sickle cell anemia. J Pediatr Endocrinol Metab 2013;26:1205-7.

Jarrett OO, Olorundare EI. Type 1 diabetes mellitus in a known sickle cell anaemia patient: a rare combination in Nigeria. Afr J Med Med Sci 2014;43:177-81.

Morrison JC, Schneider JM, Kraus AP, Kitabchi AE. The prevalence of diabetes mellitus in sickle cell hemoglobinopathies. J Clin Endocrinol Metab 1979;48:192-5.

WHO. Diabetes Country Profiles. Qatar, 2016.

Mohamed AA, Al-Qurashi F, Whitford DL. Does Sickle Cell Disease Protect Against Diabetes Mellitus?: Cross-sectional study. Sultan Qaboos Univ Med J 2015;15:e116-e 9.

Fung EB, Harmatz PR, Lee PD, et al. Multi-Centre study of Iron overload research group. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol 2006;135:574–82.

Yavropoulou MP, Pikilidou M, Pantelidou D, et al. Insulin secretion and resistance in normoglycemic patients with sickle cell disease. Hemoglobin 2017;41:6–11.

Smiley D, Dagogo-Jack S, Umpierrez G. Therapy insight: metabolic and endocrine disorders in sickle cell disease. Nat Clin Pract Endocrinol Metab 2008;4:102–9.

Mandese V, Bigi E, Bruzzi P, et al. Endocrine and metabolic complications in children and adolescents with Sickle Cell Disease: an Italian cohort study. BMC Pediatr 2019;19(1):56.

Alsultan AI, Seif MA, Amin TT, Naboli M, Alsuliman AM. Relationship between oxidative stress, ferritin and insulin resistance in sickle cell disease. Eur Rev Med Pharmacol Sci 2010;14:527–38,

Al Harbi M, Khandekar R, Kozak I, Schatz P. Association between sickle cell trait and the prevalence and severity of diabetic retinopathy. PloS One 2016;11:e0159215.

Zhou J, Han J, Nutescu EA, et al. Similar burden of type 2 diabetes among adult patients with sickle cell disease relative to African Americans in the U.S. population: a six-year population-based cohort analysis. Br J Haematol 2019;185:116-27.

Diaw M, Pialoux V, Martin C, et al. Sickle cell trait worsens oxidative stress, abnormal blood rheology, and vascular dysfunction in type 2 diabetes. Diabetes Care 2015;38:2120–7

Badawy SM, Payne AB. Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus. Blood Adv 2019;3:3297-306.

Gordon D K, Hussain M, Kumar P, Khan S, Khan S. The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability. Cureus 2020;12(8): e9685.

Reid HL, Famodu AA, Photiades DP, Osamo ON. Glycosylated haemoglobin HbA1c and HbS1c in non-diabetic Nigerians. Trop Geogr Med 1992;44:126-30.

Schnedl WJ, Trinker M, Lipp RW. HbA1c determination in patients with hemoglobinopathies. Diabetes Care 1999;22:368-9.

Kosecki SM, Rodgers PT, Adams MB. Glycemic monitoring in diabetics with sickle cell plus beta-thalassemia hemoglobinopathy. Ann Pharmacother 2005;39:1557-60.

Lacy ME, Wellenius GA, Sumner AE, et al. Association of Sickle Cell Trait With Hemoglobin A1c in African Americans. JAMA 2017;317:507-15.

Koduri PR. Iron in sickle cell disease: a review why less is better. Am J Hematol. 2003;73:59-63.

Lucania G, Vitrano A, Filosa A,Maggio A.Chelation treatment in sickle-cell-anaemia: much ado about nothing? Br J Haematol.2011;154:545–55







How to Cite

Soliman AT, De Sanctis V, Yassin M, Alshurafa A, Ata F, Nashwan A. Blood transfusion and iron overload in patients with Sickle Cell Disease (SCD): Personal experience and a short update of diabetes mellitus occurrence. Acta Biomed [Internet]. 2022 Aug. 31 [cited 2024 Jul. 20];93(4):e2022291. Available from: