Introduction: Hemoglobinopathies are a group of genetic disorders of hemoglobin (Hb) structure or synthesis. They are among the most common inherited diseases. Approximately 7% of the global population is a carrier, and 300,000–500,000 children are born with a severe Hb disorder annually. They are classified according to the impaired globin chains and whether the disorder leads to reduced production of a normal chain or an abnormal tertiary structure of globin chains. There are two types of hemoglobinopathies, sickle cell disease (SCD), and thalassemia. For years, these diseases impair the quality of life of those afflicted. Impairment in the quality of life can be due to the disease, its complications or even as a result of its treatment. Mortality and morbidity from these diseases are staggering, and many of those affected do not survive to adulthood. However, as medical science develops, the etiology and treatment of the disease are now almost completely unraveled. These have enabled the provision of quality care to those affected with concomitant improvement in quality of life and survival for those affected. Those that get pregnant now constitute a high-risk cohort who require meticulous quality prenatal, intrapartum, and postpartum care to survive. Such care is widely available in developed countries; however, in developing countries where the burden of the disease is highest, such care is scarce, and maternal and perinatal morbidity and mortality remain high.
Methods: This review is done through extensive literature search from various sources. It first discusses sickle disease and then the thalassemias.
Aims: The review is aimed at summarizing the disease and its management in pregnancy with the hope that physicians will use the acquired knowledge of the disease and the various strategies to improve the quality of life and survival of patients and their fetuses in pregnancy and postpartum.
Conclusion: Hemoglobinopathies are a group of genetic disorders of hemoglobin (Hb) structure or synthesis. There are two types of hemoglobinopathies, sickle cell disease (SCD), and thalassemia. Mortality and morbidity from these diseases are staggering, and many of those affected do not survive until adulthood. Those that get pregnant now constitute a high-risk cohort who require meticulous quality prenatal, intrapartum, and postpartum care to survive. The aim of the review is to provide current overview of the disease and its management with the hope that physicians will use the knowledge to improve the quality of life and survival of pregnant women afflicted with the disease to go through pregnancy safely.
Aliyu Labaran Dayyabu. Haemoglobinopathies in perinatal medicine: challenges in management. In: Chervenak FA, Kupesic Plavsic S, Kurjak A. The fetus as a patient: current perspectives. Jaypee Brothers, New Delhi, 2019, pp. 1–18.
Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood 2010;115(22):4331–4336. DOI: 10.1182/blood-2010-01-251348
Petrakos G, Andriopoulos P, Tsironi M. Pregnancy in women with thalassemia: challenges and solutions. Int J Womens Health 2016;8:441–451. DOI: 10.2147/IJWH.S89308
Kwawukume E.Y. Sickle cell disease in Pregnancy. In: Comprehensive Obstetrics in the Tropics. First edition, Chapter 39. 2008, pp. 303–311.
Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. 1910. Yale J Biol Med 1910;74(3):179–184. DOI: 10.1001/jama.2014.11011
Pauling L, Itano HA, Singer SJ, et al. Sickle cell anemia, a molecular disease. Science 1949;110(2865):543–548. DOI: 10.1126/science.110.2865.54
Neel JV. The inheritance of sickle cell anemia. Science 1949;110(2846):64–66. DOI: 10.1126/science.110.2846.64
Serjeant G (1985) ‘Sickle cell disease’, Oxford University Press, Oxford, PP 13–19
Angastiniotis M, Modell B, Englezos P, et al. Prevention and control of haemoglobinopthies. Bull World Health Organ 1995;73(3):375–386.
Serjeant GR. Sickle cell disease. Lancet 1997;350(9079):725–730. DOI: 10.1016/S0140-6736(97)07330-3
Diallo D, Tchernia G. Sickle cell disease in Africa. Curr Opin Hematol 2002;9(2):111–116. DOI: 10.1097/00062752-200203000-00005
Agboola A. Anemia in pregnancy, sickle cell disease. Agboola A (ed). Textbook of obstetrics and gynecology for medical students. 2nd edition. Heinemann Educational Books (Nigeria) Plc. pp. 331–339.
Streetley A, Latinovic R, Hall K, et al. Implementation of universal newborn bloodspot screening for sickle cell disease and other clinically significant haemoglobinopthies in England: screening results for 2005–7. J Clin Pathol 2009;62(1):26–30. DOI: 10.1136/jcp.2008.058859
Green-top Guideline, No.61 July 2011
Tonniges TF. Serving the family from birth to the medical home: newborn screening: a blueprint for the future—a call for a national agenda on state newborn screening programs. Paediatrics 2000;106(2):389–422. DOI: 10.1542/peds.106.S2.389
The Council of Regional Networks for. Genetics Services (corn), Atlanta, December 1995
Tuck S, White JM. Sickle cell disease. In: JWW Studd (ed) Prog Obstet Gynaecol 1981;1:70–79. https://doi.org/10.1111/j.1471-0528.1983.tb08893.x
Kobak AJ, Stein PJ, Daro AF. Sickle cell anaemia in pregnancy. A review of literature and report of six cases. Am J Obstet Gynecol 1941;41(5):811–821. DOI: 10.1016/S0002-9378(41)90869-4
Rajab KE, Issa AA, Mohammed AM, et al. Sickle cell disease and pregnancy in Bahrain. Int J Gynaecol Obstet 2006;93(2):171–175. DOI: 10.1016/j.ijgo.2006.02.007
Smith JA, Espeland M, Bellevue R, et al. Pregnancy in sickle cell disease: experience of the cooperative study of sickle cell disease. Obstet Gynecol 1996;87(2):199–204. DOI: 10.1016/0029-7844(95)00367-3
Al Jama FE, Gasem T, Burshaid S, et al. Pregnancy outcome in patients with homozygous sickle cell disease in a university hospital, Eastern Saudi Arabia. Arc Gynecol Obstet 2009;280(5):793–797. DOI: 10.1007/s00404-009-1002-7
el-Shafei AM, Sandhu AK, Dhaliwal JK. Maternal mortality in Bahrain with special reference to sickle cell disease. Aust N Z J Obstet Gynaecol 1988;28(1):41–44. DOI: 10.1111/j.1479-828x.1988.tb01609.x
Villers MS, Jamison MG, De Castro LM, et al. Morbidity associated with sickle cell disease in pregnancy. Am J Obstet Gynecol 2008;199(2):125.e1–125.e5. DOI: 10.1016/j.ajog.2008.04.016
Afolabi BB, Iwuala NC, Iwuala IC, et al. Morbidity and mortality in sickle cell pregnancies in Lagos, Nigeria: a case control study. J Obstet Gynaecol 2009;29(2):104–146. DOI: 10.1080/01443610802667112
Tuck SM, Studd JW, White JM. Pregnancy in sickle cell disease in the UK. Br J Obstet Gynaecol 1983;90(2):112–117. DOI: 10.1111/j.1471-0528.1983.tb08893.x
Sun PM, Wilburn W, Raynor BD, et al. Sickle cell disease in pregnancy: twenty years experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol 2001;184(6):1127–1130. DOI: 10.1067/mob.2001.115477
Serjeant GR, Loy LL, Crowther M, et al. Outcome of pregnancy in homozygous sickle cell disease. Obstet Gynecol 2004;103(6):1278–1285. DOI: 10.1097/01.AOG.0000127433.23611.54
Chakravarty EF, Khanna D, Chung L. Pregnancy outcomes in systemic sclerosis, primary pulmonary hypertension, and sickle cell disease. Obstet Gynecol 2008;111(4):927–934. DOI: 10.1097/01.AOG.0000308710.86880.a6
Ranney HM, Sharma V. Structure and function of haemoglobin. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ. (eds) Williams’ Haematology, 5th edn. New York: McGraw-Hill, 1995;417.
Chernoff AI. The amino acid composition of haemoglobin: IV. The preparation of pure polypeptide chains of human haemoglobins. J Chromatogr 1965;17:140–148. DOI: 10.1016/S0021-9673(00)99844-3
Progress in Obstetrics and Gynaecology 16
Jaffe RH. Die Schelzellenanamie. Virch Arch Pathol Anat 1927;265:452–471.
Ballas SK, Larner J, Smith ED, et al. Rheologic predictors of the severity of the painful sickle cell crises. Blood 1988;72(4):1216–1223. DOI: 10.1182/blood.V72.4.1216.1216
Martin Jr JN, Files J, Morrison JC. Sickle cell cell crises. In: Clark SL, Cotton DV, Hankins GDV, Phelan JP. (eds) Critical care Obstetrics, 2nd edn. Cambridge, MA: Blackwell 1991;212.
Beutler E. The sickle cell disease related disorders. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ. (eds) Williams’ Haematology, 5th edn. New York: McGraw-Hill, 1995;616.
Howard RJ, Tuck SM, Pearson TC. Pregnancy in sickle cell disease in the UK: results of a multicentre survey of the effect of prophylactic blood transfusion on maternal and fetal outcome. Br J Obstet Gynaecol 1995;102(12):947–951. DOI: 10.1111/j.1471-0528.1995.tb10900.x
Perrine RP, Brown MJ, Clegg JB, et al. Benign sickle-cell anaemia. Lancet 1972;2(7788):1163–1167. DOI: 10.1016/s0140-6736(72)92592-5
Pembrey ME, Wood WG, Weatherall DJ, et al. Fetal haemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia. Brit J Haematol 1978;40(3):415–429. DOI: 10.1111/j.1365-2141.1978.tb05813.x
Weatherall DJ, Clegg JB, Blankston J, et al. A new sickling disorder resulting from interaction of the genes for haemoglobin S and α-thalassemia. Brit J Haemtol 1969;17(6):517–526. DOI: 10.1111/j.1365-2141.1969.tb01402.x
Warsy AS. Frequency of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. A study in Saudi Arabia. Hum Hered 1985;35(3):143–147. DOI: 10.1159/000153534
Johnson K, Posner SF, Biermann J, et al. Recommendation to improving preconception health and healthcare; United States. MMWR 2006;55(No. RR–06):1–23
Lindenbaum J, Klipstein FA. Folic acid deficiency in sickle-cell anemia. N Engl J Med 1963;269:875–882. DOI: 10.1056/NEJM196310242691701
Charache S, Niebyl JR. Pregnancy in sickle cell disease. Clin Haematol 1985;14(3):729–746. DOI: 10.1016/S0308-2261(21)00502-6
Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the multicenter study of hydroxyurea in sickle cell anemia. N Engl J Med 1995;332(20):1317–1322. DOI: 10.1056/NEJM199505183322001
Diav-Citrin O, Hunnisett L, Sher GD, et al. Hydroxyurea use during pregnancy: a case report in sickle cell disease and a review of literature. Am J Hematol 1999;60(2):148–150. DOI: 10.1002/(sici)1096-8652(199902)60:2<148::aid-ajh12>3.0.co;2-i
Byrd DC, Pitts SR, Alexander CK. Hydroxyurea in two pregnant women with sickle cell anemia. Pharmacotherapy 1999;19(12):1459–1462. DOI: 10.1592/phco.19.18.1459.30901
Foucan L, Bourhis V, Bangou J, et al. A randomized trial of captopril for microalbuminuria in normotensive adults with sickle cell anemia. Am J Med 1998;104(4):339–342. DOI: 10.1016/s0002-9343(98)00056-4
McKie KT, Hanevold CD, Hernandez C, et al. Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. J Pediatr Hematol Oncol 2007;29(3):140–144. DOI: 10.1097/MPH.0b013e3180335081
Gaston MH, Verter JI, Woods G, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 1986;314(25):1593–1599. DOI: 10.1056/NEJM198606193142501
Sickle cell Society. Standards for the Clinical Care of Adults with Sickle Cell Disease in the UK. London: Sickle Cell Society; 2008.
Working party of the British committee for standards in haematology clinical haematology task force. Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. BMJ 1996;312(7028):430–434. DOI: 10.1136/bmj.312.7028.430
Ataga KI, Moore CG, Jones S, et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol 2006;134(1):109–115. DOI: 10.1111/j.1365-2141.2006.06110.x
Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004;350(9):886–895. DOI: 10.1056/NEJMoa035477
Clarkson JG. The ocular manifestation of sickle-cell disease: a prevalence and natural history study. Trns Am Opthalmol Soc 1992;90:481–504. PMID: 1494832; PMCID: PMC1298447.
Royal College of Obstetricians and Gynaecologists. Amniocentesis and chorionic villus sampling. Green-top Guideline No. 8. London: RCOG; 2010 [http://www.rcog.org.uk/womens-health/clinical-guidance/amniocentesis-andchorionic-villus-sampling-green-top-8]
Powars DR, Sandhu M, Niland-Weis J, et al. Pregnancy in sickle cell disease. Obstet Gynecol 1986;67(2):217–228. DOI: 10.1097/00006250-198602000-00012
Maeda T, Wakasawa T, Shima Y, et al. Role of polyamines derived from arginine in differentiation and proliferation of human blood cells. Biol Pharm Bull 2006;29(2):234–239. DOI: 10.1248/bpb.29.234
Tuck SM, Studd JW, White JM. Sickle cell disease in pregnancy complicated by anti-U antibody. Case report. Br J Obstet Gynaecol 1982;89(1):91–92. DOI: 10.1111/j.1471-0528.1982.tb04645.x
Cunningham FG, Pritchard JA, Mason R, et al. Prophylactic transfusions of normal red blood cells during pregnancies complicated by sickle cell hemoglobinopthies. Am J Obstet Gynecol 1979;135(7):994–1003. DOI: 10.1016/0002-9378(79)90825-1
Morrison JC, Schneider JM, Whybrew WD, et al. Prophylactic transfusion in pregnant patients with sickle hemoglobinopthies: benefit versus risk. Obstet Gynecol 1980;56(3):274–280. PMID: 7422165.
Tuck SM, James CE, Brewster EM, et al. Prophylactic blood transfusion in maternal sickle cell syndromes. Br J Obstet Gynaecol 1987;94(2):121–125. DOI: 10.1111/j.1471-0528.1987.tb02337.x
Koshy M, Burd L, Wallace D, et al. Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperatve study. N Engl J Med 1988;319(22):1447–1452. DOI: 10.1056/NEJM198812013192204
Aken'Ova YA, Adeyefa I, Okunade M. Ferritin and serum iron levels in adult patients with sickle cell anaemia at Ibadan, Nigeria. Afr J Med Sci 1997;26(1-2):39–41. DOI: 10.1155/2015/386451
Akinyanju OO, Nnatu SNN, Ogedengbe OK. Antenatal iron supplementation in sickle cell disease. Int J Gynaecol Obstet 1987;25(6):433–436. DOI: 10.1016/0020-7292(87)90057-9
Duley L, Henderson-Smart DJ, Meher S, et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007;(2):CD004659. DOI: 10.1002/14651858.CD004659.pub2
National Institute for Health and Clinical excellence
Rees DC, Olujohungbe AD, Parker NE, et al. Guidelines for the management of acute painful crisis in sickle cell disease. Br J Haematol 2003;120(5):744–752. DOI: 10.1046/j.1365-2141.2003.04193.x
Anyaegbunam A, Morel MI, Merkatz IR. Antepartum fetal surveillance tests during sickle cell crisis. Am J Obstet Gynecol 1991;165(4):1081–1083. DOI: 10.1016/0002-9378(91)90475-7
Anyaegbunam A, Mikhail M, Axioitis C, et al. Placental histology and placental/fetal weight ratios in pregnant women with sickle cell disease: relationship to pregnancy outcome. J Assoc Acad Minor Phys 1994;5(3):123–125. PMID: 7949824.
Camous J, N'da A, Etienne-Julan M, et al. Anaesthetic management of pregnant women with sickle cell disease–effect on postnatal sickling complications. Can J Anaesth 2008;55(5):276–283. DOI: 10.1007/BF03017204
De Ceulaer K, Gruber C, Hayes R, et al. Medroxyprogesterone acetate and homozygous sickle-cell disease. Lancet 1982;2(8292):229–231. DOI: 10.1016/s0140-6736(82)90320-8
Legardy JK, Curtis KM. Progesterone-only pill use among women with sickle cell anemia: a systematic review. Contraception 2006;73(2):195–204. DOI: 10.1016/j.contraception.2005.08.010
Bauer DE, Orkin SH. Update on fetal hemoglobin gene regulation in hemoglobinopathies. Curr Opin Pediatr 2011;23(1):1–8. DOI: 10.1097/MOP.0b013e3283420fd0
Old JM. Screening and genetic diagnosis of haemoglobin disorders. Blood Rev 2003;17(1):43–53. DOI: 10.1016/s0268-960x(02)00061-9
Cohen AR, Galanello R, Pennell DJ, et al. Thalassemia. Hematology Am Soc Hematol Educ Program 2004;2004:14–34. DOI: 10.1182/asheducation-2004.1.14
De Sanctis V, Soliman AT, Elsedfy H, et al. Growth and endocrine disorders in thalassemia: the international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab 2013;17(1):8–18. DOI: 10.4103/2230-8210.107808
De Sanctis V. Growth and puberty and its management in thalassemia. Horm Res 2002;58(1):72–79. DOI: 10.1159/000064766
Roussou P, Tsagarakis NJ, Diamanti-Kandarakis E, et al. Beta-thalassemia major and female fertility: the role of iron and iron-induced oxidative stress. Anemia 2013;2013(2):617204. DOI: 10.1155/2013/617204
Agarwal A, Allamaneni SS. Role of free radicals in female reproductive diseases and assisted reproduction. Reprod Biomed Online 2004;9(3):338–347. DOI: 10.1016/s1472-6483(10)62151-7
Al-Gubory KH, Garrel C, Faure P, et al. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress. Reprod Biomed Online 2012;25(6):551–560. DOI: 10.1016/j.rbmo.2012.08.004
Mahachoklertwattana P, Yimsumruay T, Poomthavorm P, et al. Acute effects of blood transfusion on growth hormone and insulin-like growth factor-1 levels in children with thalassemia. Horm Res Paediatr 2011;75(4):240–245. DOI: 10.1159/000321189
Soliman A, Yassin M, El-Awwa A, et al. Acute effects of blood transfusion on pituitary gonadal axis and sperm parameters in adolescents and young men with thalassemia major: a pilot study. Fertil Steril 2012;98(3):638–643. DOI: 10.1016/j.fertnstert.2012.05.047
De Sanctis V, Elsedfy H, Soliman AT, et al. Acquired hypogonadotropic hypogonadism (AHH) in thalassemia major patients: an underdiagnosed condition?. Mediterr J Haematol Infect Dis 2016;8(1):e2016001. DOI: 10.4084/MJHID.2016.001
Kiess W, Reich A, Meyer K, et al. A role for leptin in sexual maturation and puberty?. Horm Res 1999;51(3):55–63. DOI: 10.1159/000053163
Perrone L, Perrotta S, Raimondo P, et al. Inappropriate leptin secretion in thalassemia: a potential cofactor of pubertal timing derangement. J Pediatr Endocrinol Metab 2003;16(6):877–881. DOI: 10.1515/jpem.2003.16.6.877
De Sanctis V, D'Ascola G, Wonke B. The development of diabetes mellitus and chronic liver disease in long term chelated beta thalassemic patients. Postgrad Med J 1986;62(731):831–836. DOI: 10.1136/pgmj.62.731.831
Singer ST, Vichinsky EP, Gildengorin G, et al. Reproductive capacity in iron overloaded women with thalassemia major. Blood 2011;118(10):2878–2881. DOI: 10.1182/blood-2011-06-360271
Skordis N, Petrikkos L, Toumba M, et al. Update on fertility in thalassemia major. Pediatr Endocrinol Rev 2004;2(2):296–302.
De Scantis V, Perera D, Katz M, et al. Spermatozoal DNA damage in patients with B thalassemia syndromes. Pediatr Endocrinol Rev 2008;6(1):185–189.
Alpendurada F, Smith GC, Carpenter JP, et al. Effects of combined deferiprone with deferoxamine on right ventricular function in thalassemia major. J Cardiovasc Magn Reson 2012;14(1):8. DOI: 10.1186/1532-429X-14-8
Pennell D, Porter JB, Cappellini MD, Li CK, Aydinok Y, Lee CL, et al. Efficacy and safety deferasirox (ExjadeR) in reducing cardiac iron in patients with B-thalassemia major: results from the cardiac sub-study of the EPIC trial [abstract]. Blood 2008;112(ASH Annual Meeting Abstract): Abstract, 3873 [http://abstract.haematologylibrary.org/cgi/content/abstract/112/11/3873]
Barry M, Flynn DM, Letsky EA, et al. Long-term chelation therapy in thalassemia major: effect on liver iron concentration, liver histology, and clinical progress. Br Med J 1974;2(5909):16–20. DOI: 10.1136/bmj.2.5909.16
Schnebli H.P. Final Report: Preclinical evaluation of CGP 37 391(L1). Schnebli HP, editor. ERS 62/93;1993. pp. 2–30.
Khoury S, Odeh M, Oettinger M. Deferoxamine treatment for acute iron intoxication in pregnancy. Acta Obstet Gynecol Scand 1995;74(9):756–757. DOI: 10.3109/00016349509021190
Singer ST, Vichinsky EP. Deferoxamine treatment during pregnancy: is it harmful? Am J Hematol 1999;60(1):24–26. DOI: 10.1002/(sici)1096-8652(199901)60:1
de Assis RA, Ribeiro AA, Kay FU, et al. Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients. Eur J Radiol 2012;81(7):1465–1470. DOI: 10.1016/j.ejrad.2011.03.077
National Institute for Health and Clinical Excellence. Diabetes in pregnancy: Management of diabetes and its complications from pre-conception to the postnatal period. NICE clinical guideline 63. Manchester: Nice; 2008.
Spencer DH, Grossman BJ, Scott MG. Red cell transfusion decreases hemoglobin A1c in patients with diabetes. Clin Chem 2011;57(2):344–346. DOI: 10.1373/clinchem.2010.157321
De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97(8):2543–2565. DOI: 10.1210/jc.2011-2803
Kirk P, Roughton M, Porter JB, et al. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation 2009;120(20):196–198. DOI: 10.1161/CIRCULATIONAHA.109.874487
Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89(3):2621.
Walsh JM, McGowan CA, Kilbane M, et al. The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth. Reprod Sci 2013;20(5):536–541. DOI: 10.1177/1933719112459222
Thompson AA, Cunningham MJ, Singer ST, et al. Red cell alloimmunization in a diverse population of transfused patients with thalassemia. Br J Haematol 2011;153(1):121–128. DOI: 10.1111/j.1365-2141.2011.08576.x
Royal College of Obstetricians and Gynaecologists. The management of women with red cell. Antibodies during pregnancy. Green-top Guideline No.65. London: RCOG; 2014.
Royal College of Obstetrician and Gynaecologists. Blood Transfus. Royal College of Obstetrician and Gynaecologists. Blood Transfusions in Obstetrics. Green-top Guideline No. 47. London: RCOG; 2007.
Davis BA, Porter JB. Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. Blood 2000;95(4):1229–1236. DOI: 10.1182/blood.V95.4.1229.004k32_1229_1236
Anderson LJ, Westwood MA, Holden S, et al. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. Br J Haematol 2004;127(3):348–355. DOI: 10.1111/j.1365-2141.2004.05202.x
Davis BA, O'Sullivan C, Jarrit PH, et al. Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major. Blood 2004;104(1):263–269. DOI: 10.1182/blood-2003-08-2841
Lekawanvijit S, Chattipakorn N. Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 2009;25(4):213–218. DOI: 10.1016/s0828-282x(09)70064-9
Begley CM, Gyte GM, Devane D, et al. Active versus expectant management for women in the third stage of labor. Cochrane Database Syst Rev 2011;(11):CD007412. DOI: 10.1002/14651858.CD007412.pub3
National Institute for Health and Clinical Excellence. Intrapartum care: Care of healthy women and their babies during childbirth. NICE clinical guideline 55. Manchester: NICE; 2007.
Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002;99(1):36–43. DOI: 10.1182/blood.v99.1.36
Taher A, Isma'eel H, Mehio G, et al. Prevalence of thromboembolic events among 8,860 patients with thalassemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96(4):488–491. DOI: 10.1160/TH06-05-0267
Royal College of Obstetrician and Gynaecologists. Reducing the Risk of Thrombosis and Embolism during Pregnancy and the Puerperium. Green-top Guideline No. 37a. London: RCOG; 2009.