Sickle Cell Anemia as the First in the Hierarchy for Cardiac Alterations, Drives Attention to the Whole Spectrum of Hemolytic Anemias

Keywords
Cardiovascular Diseases; Anemia, Sickle Cell; Anemia, Hemolytic; Hemonoglobinopathies/complications: Hypertension, Pulmonary/complications; Diagnostic; Imaging/methods

The focus on the cardiac repercussions of Hemolytic Anemias has been greatly emphasized by publications issued by academic and official government documents that are easily accessed by all health professionals, mainly articles that aim at Sickle Cell Anemia¹,² and Thalassemia.³,⁴

Sickle cell disease is the most frequent genetic hemoglobinopathy worldwide.⁵ Thanks to the improvement of the medical management of these patients, their life expectancy has improved in recent years.⁶ However, cardiopulmonary complications remain one of the main causes of death in adult patients with sickle cell disease.⁷

Current knowledge about cardiac involvement in sickle cell disease is mainly derived from studies of sickle cell anemia genotypes.⁸,⁹ Pulmonary systolic hypertension, assessed by increased tricuspid regurgitation rate (TRV) and left ventricular diastolic dysfunction diagnosed by ultrasound, has been associated with increased mortality and is characteristic of sickle cell anemia characterized by hemoglobin S⁸-¹⁰ homozygosis. On the other hand, hemoglobin SC disease (HbSC), resulting from compound heterozygosity for two different mutations of the beta-globin gene, has a different pathophysiology¹¹ and a more attenuated clinical profile of clinical presentation.¹² Patients with HbSC usually have a relatively low hemolysis rate and only mild anemia.¹¹ In addition, the prevalence of obesity is higher in patients with HbSC than in sickle cell anemia.¹³ This non-hematological comorbidity may contribute to cardiac remodeling.¹⁴ Currently, echocardiography is recommended for routine follow-up of all patients with sickle cell disease, regardless of genotype.

Despite advances in the management of thalassemia major, heart disease remains the main cause of mortality in patients with this disease.¹⁵

Cardiac involvement in thalassemia encompasses a spectrum of disorders, including myocardial dysfunction, arrhythmias, hypertension and peripheral vascular disease.¹⁶ Although cardiac siderosis (accumulation of iron in cardiac myocytes) as a consequence of repeated blood transfusions is considered the main etiological factor for myocardial dysfunction in transfusion-dependent patients, other pathophysiological mechanisms are increasingly recognized, especially in patients not dependent on transfusion.¹⁷ Managing cardiac complications in thalassemia major depends on treating the underlying pathophysiology, which is often iron overload.

Susceptibility to iron toxicity and its phenotypic manifestations vary widely among thalassemia patients. At present, the detection of myocardial iron deposition by cardiac magnetic resonance imaging remains the best marker of future cardiac dysfunction.¹⁸

Echocardiographic studies suggest that myocardial deposition can directly affect left ventricular contractility, while in others, it may cause myocardial restriction of the left ventricle with concomitant pulmonary hypertension and predominant right heart failure.¹⁹

The rarest forms of Hemolytic Anemias have also to be investigated because they present particular characteristics that involve their clinical follow-ups.²⁰

• Short Editorial related to the article: Prevalence of Cardiovascular Complications in Individuals with Sickle Cell Anemia and Other Hemoglobinopathies: A Systematic Review

Referências

• ¹
  Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Especializada. Manual da anemia falciforme para a população. Brasília: 2007. 24 p. (Série A. Normas e Manuais Técnicos). ISBN: 978-85-334-1327-6. https://www.nupad.medicina.ufmg.br/wp-content/uploads/2016/12/Manual-da-Anemia-Falciforme-para-a-populacao.pdf
  » https://www.nupad.medicina.ufmg.br/wp-content/uploads/2016/12/Manual-da-Anemia-Falciforme-para-a-populacao.pdf
• ²
  Brasil. Ministerio da Saúde. ANVISA.Manual de Diagnóstico e Tratamento de Doença Falciformes. Brasília; 2001. 142 p. ISBN 85-88233-04-5. https://bvsms.saude.gov.br/bvs/publicacoes/anvisa/diagnostico.pdf
  » https://bvsms.saude.gov.br/bvs/publicacoes/anvisa/diagnostico.pdf
• ³
  Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Especializada e Temática. Orientações para diagnóstico e tratamento das Talassemias Beta. Brasilia; 2016. 184 p. ISBN 978-85-334-2358-9.
• ⁴
  Brasil. Ministério da Saúde Secretaria de Atenção à Saúde Departamento de Atenção Hospitalar e de Urgência. Coordenação-Geral de Sangue e Hemoderivados. Área de Assessoramento Técnico às Talassemias. Disponível em: https://bvsms.saude.gov.br/bvs/folder/talassemias_folder.pdf
  » https://bvsms.saude.gov.br/bvs/folder/talassemias_folder.pdf
• ⁵
  Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6. doi: 10.1182/blood-2010-01-251348
  » https://doi.org/10.1182/blood-2010-01-251348
• ⁶
  Chaturvedi S, DeBaun MR. Evolution of sickle cell disease from a life-threatening disease of children to a chronic disease of adults: The last 40 years. Am J Hematol. 2016;91(1):5-14. doi: 10.1002/ajh.24235
  » https://doi.org/10.1002/ajh.24235
• ⁷
  Fitzhugh CD, Lauder N, Jonassaint JC, Telen MJ, Zhao X, Wright EC, et al. Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am J Hematol. 2010;85(1):36-40. doi: 10.1002/ajh.21569
  » https://doi.org/10.1002/ajh.21569
• ⁸
  Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350(9):886-95. doi: 10.1056/NEJMoa035477
  » https://doi.org/10.1056/NEJMoa035477
• ⁹
  Sachdev V, Machado RF, Shizukuda Y, Rao YN, Sidenko S, Ernst I, et al. Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. J Am Coll Cardiol. 2007;49(4):472-9. doi: 10.1016/j.jacc.2006.09.038
  » https://doi.org/10.1016/j.jacc.2006.09.038
• ¹⁰
  Cabrita IZ, Mohammed A, Layton M, Ghorashian S, Gilmore A, Cho G, et al. The association between tricuspid regurgitation velocity and 5-year survival in a North West London population of patients with sickle cell disease in the United Kingdom. Br J Haematol. 2013;162(3):400-8. doi: 10.1111/bjh.12391
  » https://doi.org/10.1111/bjh.12391
• ¹¹
  Nagel RL, Fabry ME, Steinberg MH. The paradox of hemoglobin SC disease. Blood Rev. 2003;17(3):167-78. doi: 10.1016/s0268-960x(03)00003-1
  » https://doi.org/10.1016/s0268-960x(03)00003-1
• ¹²
  Lionnet F, Hammoudi N, Stojanovic KS, Avellino V, Grateau G, Girot R, et al. Hemoglobin sickle cell disease complications: a clinical study of 179 cases. Haematologica. 2012;97(8):1136-41. doi: 10.3324/haematol.2011.055202
  » https://doi.org/10.3324/haematol.2011.055202
• ¹³
  Chawla A, Sprinz PG, Welch J, Heeney M, Usmani N, Pashankar F, et al. Weight status of children with sickle cell disease. Pediatrics. 2013;131(4):e1168-e1173. doi: 10.1542/peds.2012-2225
  » https://doi.org/10.1542/peds.2012-2225
• ¹⁴
  Kim SH, Després JP, Koh KK. Obesity and cardiovascular disease: friend or foe? Eur Heart J. 2016;37(48):3560-8. doi: 10.1093/eurheartj/ehv509
  » https://doi.org/10.1093/eurheartj/ehv509
• ¹⁵
  Fattizzo B, Giannotta JA, Cecchi N, Barcellini W. Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias. Orphanet J Rare Dis. 2021;16(1):415. doi: 10.1186/s13023-021-02036-4
  » https://doi.org/10.1186/s13023-021-02036-4
• ¹⁶
  Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353(11):1135-46. doi: 10.1056/NEJMra050436
  » https://doi.org/10.1056/NEJMra050436
• ¹⁷
  Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci. 1998;850:191-201. doi: 10.1111/j.1749-6632.1998.tb10475.x
  » https://doi.org/10.1111/j.1749-6632.1998.tb10475.x
• ¹⁸
  Wood JC. Cardiac iron across different transfusion-dependent diseases. Blood Rev. 2008;22 Suppl 2(Suppl 2):S14-S21. doi: 10.1016/S0268-960X(08)70004-3
  » https://doi.org/10.1016/S0268-960X(08)70004-3
• ¹⁹
  Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) [Internet]. 3rd ed. Nicosia (CY): Thalassaemia International Federation; 2014. PMID:25610943
• ²⁰
  Kremastinos DT. Heart failure in beta-thalassemia. Congest Heart Fail. 2001;7(6):312-4. doi: 10.1111/j.1527-5299.2001.00259.x
  » https://doi.org/10.1111/j.1527-5299.2001.00259.x
• ²¹
  Lopes A, Dantas MT, Ladeia AMT. Prevalence of Cardiovascular Complications in Individuals with Sickle Cell Anemia and Other Hemoglobinopathies: A Systematic Review. Arq Bras Cardiol. 2022; 119(6):893-899.

Publication Dates

• Publication in this collection
  19 Dec 2022
• Date of issue
  Dec 2022