Genetic counseling for individuals with hemoglobin disorders and for their relatives: a systematic literature review

Asesoramiento genético para individuos con alteraciones de las hemoglobinas y sus familiares: revisión sistemática de literatura

Tatiana Dela-Sávia Ferreira Elisângela de Paula Silveira-Lacerda Marco Tulio Antonio García-Zapata About the authors

Abstracts

Objective: To identify genetic counseling programs that do not encourage therapeutic abortion for individuals with hemoglobin disorders and/or for their relatives. Method: Systematic literature review of articles published from 2001 to 2012 that are located in the PubMed, LILACS, SciELO and SCOPUS databases using keywords in Portuguese, English and Spanish and that met the inclusion and exclusion criteria described on a standardized form. Results: A total of 409 articles were located, but only eight (1.9%) were selected for analysis. Conclusion: Although seldom mentioned in the literature, educational/preventive programs targeting hemoglobinopathies are feasible and allow the affected individuals to acquire knowledge on the consequences of this condition and their odds of transmitting it.



Genetic counseling; Hemoglobinopathies; Disease prevention; Health education; Review


Objetivo: Identificar programas de asesoramiento genético sin incentivo al aborto terapéutico para individuos con alteraciones de las hemoglobinas y/o sus familiares. Método: Revisión sistemática de literatura realizada en las bases de datos PubMed, LILACS, SciELO y SCOPUS por artículos publicados de 2001 a 2012, utilizando descriptores en portugués, inglés y español, según formularios estandarizados que abarcaban criterios de inclusión y exclusión. Resultados: De los 409 estudios encontrados solo ocho (1,9%) fueron seleccionados. Conclusión: Los programas de educación/prevención para hemoglobinopatías, aunque rara vez encontrados en la literatura, son posibles y permiten que los individuos adquieran conocimiento acerca de las consecuencias de su disturbio y la probabilidad de trasmitirlo.

Asesoramiento genético; Hemoglobinopatías; Prevención de enfermedades; Educación en salud; Revisión


Objetivo

Identificar programas de aconselhamento genético sem incentivo ao aborto terapêutico para indivíduos com alterações das hemoglobinas e/ou seus familiares.

Método

Revisão sistemática de literatura realizada nas bases de dados PubMed, LILACS, SciELO e SCOPUS por artigos publicados de 2001 a 2012, utilizando descritores em português, inglês e espanhol, de acordo com formulários padronizados contendo critérios de inclusão e exclusão.

Resultados

Dos 409 estudos encontrados somente oito (1,9%) foram selecionados.

Conclusão

Os programas de educação/prevenção para hemoglobinopatias, embora raramente encontrados na literatura, são possíveis e permitem que indivíduos adquiram conhecimento sobre as consequências de seu distúrbio e a probabilidade de transmití-lo.


Aconselhamento genético; Hemoglobinopatias; Prevenção de doenças; Educação em saúde; Revisão


Introduction

Hemoglobinopathy is a group of disorders caused by substitutions, insertions or deletions in the coding regions of the α and/or β globin chain genes(101 Cardoso GL, Guerreiro JF. Molecular characterization of sickle cell anemia in the Northern Brazilian State of Pará. Am J Hum Biol. 2010;22(5):573-7). The clinical manifestations of these disorders exhibit quite a broad scope and are characterized by striking differences in severity(202 Belisário AR, Viana MB. Efeitos da talassemia alfa nas manifestações clínicas e hematológicas da anemia falciforme: uma revisão sistemática. Rev Med Minas Gerais. 2010;20(1):312-21). Episodes of pain are the most recurrent among such manifestations and might result in stress, anxiety, depression, frequent hospital admissions and suffering for both patients and their relatives. The most severe cases are associated with productivity loss and socioeconomic, emotional and psychological problems(303 Dias TL, Oliveira CGT, Enumo SRF, Paula KMO. A dor no cotidiano de cuidadores e crianças com anemia falciforme. Psicol USP. 2013;24(3):391-411-404 Santos MZ, Kusahara DM, Pedreira MLG. The experiences of intensive care nurses in the assessment and intervention of pain relief in children. Rev Esc Enferm USP. 2012;46(5):1074-81).

Approximately 7% of the world population currently exhibits symptoms of hemoglobinopathies(505 Carvalho FS, Dias-Penna KGB, Araújo ES, Ramos ALM, Bataus LAM. Estudo comparativo da eficiência da eletroforese alcalina em acetato de celulose na identificação de hemoglobinas utilizando diferentes tampões. Rev Bras Anal Clin. 2010;42(4):293-6). It is estimated that 4% of the Brazilian population is heterozygous for sickle cell anemia (sickle cell trait) and that 25,000 to 50,000 individuals exhibit some type of hemoglobinopathy(606 Brasil. Ministério da Saúde. Portaria n. 55, de 29 de janeiro de 2010. Protocolo Clínico e Diretrizes Terapêuticas - Doença Falciforme [Internet]. Brasília; 2010 [citado 2013 dez. 12]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/sas/2010/prt0055_29_01_2010.html
http://bvsms.saude.gov.br/bvs/saudelegis...
). This high prevalence of hemoglobinopathies emphasizes the need for educational preventive actions by means of community-based programs for early diagnosis, information, education and communication(707 Bandeira FMGC, Santos MNN, Bezerra MAM, Gomes YM, Araújo AS, Braga MC, et al. Triagem familiar para o gene HBB*S e detecção de novos casos de traço falciforme em Pernambuco. Rev Saúde Pública. 2008;42(2):234-41).

Genetic counseling is a process of communication regarding human problems related to the occurrence or risk of recurrence of genetic disorders within families(808 Fraser FC. Current issues in medical genetics. Am J Hum Genet. 1974;26(5):636-61). This process is used by counselors to help patients and families interpret the results of tests; to provide information on heredity, prevention, resources, diagnosis and follow up; and to promote informed decision-making and adaptation to the conditions of risk(909 Resta R, Biesecker BB, Bennett RL, et al. A new definition of genetic counseling: National Society of Genetic Counselors’ Task Force Report. J Genet Couns. 2006;15(2):77-83).

Genetic counseling plays a crucial role in the promotion of public health and human rights(1010 Ramalho AS, Magna LA. Aconselhamento genético do paciente com doença falciforme. Rev Bras Hematol Hemoter. 2007;29(3):229-32). In the countries in which abortion is allowed in cases of fetal abnormalities, to preserve the mother’s health or for socioeconomic reasons(1111 Henshaw SK. Induced abortion: a world review. Fam Plann Perspect. 1990;22(2):76-89), genetic counseling might encourage the termination of high-risk pregnancies as an approach to reduce the incidence of hemoglobinopathy(1212 Guedes C, Diniz D. A ética na história do aconselhamento genético: um desafio à educação médica. Rev Bras Educ Med. 2009;33(2):247-52). In Brazil, where therapeutic abortion is prohibited, genetic counseling appears to seldom be provided to families with hemoglobinopathies and is mostly performed in the neonatal period for the purpose of diagnosis and family planning or at blood donation centers(1313 Guimarães CTL, Coelho GO. A importância do aconselhamento genético na anemia falciforme. Ciênc Saúde Coletiva. 2010;15 Supl.1:1733-40).

In the current genomic era, however, genetic counseling, including its broad scope of genetic information but without encouraging therapeutic abortion, plays a crucial role in primary care, as it allows for counselors and their patients to engage in the search for preventive measures(1414 Houwink EJF, Henneman L, Westerneng M, van Luijk SJ, Cornel MC, Dinant JG, et al. Prioritization of future genetics education for general practitioners: a Delphi study. Genet Med. 2012;14(3):323-29). Thus, the aim of the present study was to identify genetic counseling programs that do not encourage therapeutic abortion for individuals with hemoglobinopathies and for their relatives by means of a systematic literature review.

Method

A systematic literature review was performed of scientific articles published from 2001 to 2012 located in the PubMed, LILACS, SciELO and SCOPUS databases to answer the following question: are individuals with hemoglobinopathies and/or their relatives provided genetic counseling without encouraging therapeutic abortion following clinical and laboratory-based diagnosis? Several keywords were tested in the attempt to answer this question, and the best combination was sickle cell anemia, thalassemia, and genetic counseling (anemia falciforme,talassemia and aconselhamento genético in Portuguese and anemia de células falciformes, talasemia and asesoramiento genético in Spanish), as located at the Virtual Health Library using the controlled vocabulary thesaurus DeCS (Descritores em Ciências da Sáude/Health Science Keywords) and PubMed using MeSH (Medical Subject Headings) (MeSH). Except for PubMed, which allows combining several keywords in searches, the terms were combined in pairs in the remainder of the databases to ensure that all of the relevant articles would be included for analysis.

The articles found were subjected to relevance tests using standardized forms composed of inclusion and exclusion criteria (Chart 1). The abstracts of the articles were analyzed first by means of relevance test I, and the articles considered to be potentially relevant for the present systematic review were subjected to relevance test II, which targeted the full text of the articles.

Articles published in English, Portuguese or Spanish from 2001 to 2012 that describe genetic counseling for individuals with sickle cell anemia or thalassemia or for individuals heterozygous for those conditions were selected for analysis. A manual search was performed based on the references cited in the selected articles to include relevant articles that could have been missed.

The articles were independently assessed by two examiners. Any instances of disagreement as to the inclusion or exclusion of studies were resolved by consensus.

Results

Based on the search criteria and keywords used, 409 articles were located in the investigated databases. Following the application of relevance test I, 345 articles were excluded according to the established inclusion and exclusion criteria, and 64 articles were considered as potentially relevant for the aims of the present review. The full text of those 64 articles was read and subjected to relevance test II, which resulted in the exclusion of another 56 articles. As a result, only eight articles were included for systematic analyses (Figure 1).

Figure 1
Process of inclusion and exclusion of articles in the present systematic review (GC: genetic counseling)

The characteristics of the included articles are summarized in Chart 2. Although the studies included different populations, most authors, who were from several different countries, agreed that genetic counseling including information/education ought to be provided to individuals with hemoglobinopathy and to their relatives as well as to individuals liable to transmit altered genes to their offspring.

Although the authors of the included studies employed various genetic counseling strategies, the purpose of the counseling was similar: to prevent the occurrence of hemoglobinopathies and to promote awareness of this subject (Chart 3).

Discussion

The results of the present review show that several scientific articles published from 2001 to 2012 correlated genetic counseling and hemoglobin disorders; however, only eight (1.9%) referred to genetic counseling that does not encourage abortion. The reason for that small number of articles might be that genetic monitoring of individuals with hemoglobinopathies began only very recently. This fact also accounts for the decision of a large proportion of authors to address several other aspects of genetic counseling, such as its relevance, the need to establish specific programs for this purpose and the successful models that should be reproduced, but without actually providing genetic counseling. In addition, the aim of genetic counseling in many countries is to reduce the incidence of hemoglobinopathy through therapeutic abortion.

Currently, non-directive genetic counseling is better accepted, as it takes the psychological and social issues of the individuals into consideration. Presently, psychosocial genetic counseling is not only based on the future reproductive decisions of an individual but also on a concern for the education, culture, personality and values of patients and their relatives to help all of them adjust to the risk of occurrence/recurrence of disease(2323 Pina-Neto JM. Aconselhamento genético. J Pediatr. 2008;84(4 Supl.):S20-6). In addition, within the context of that model, counselors attempt to help patients choose the best possible option based on their personal perspective while avoiding steering them into any particular direction(2424 Elwyn G, Gray J, Clarke A. Shared decision making and non-directiveness in genetic counselling. J Med Genet. 2000;37(2):135-8).

Overall, although the studies included in the present review had quite different designs and methods, all of them emphasized the relevance of providing genetic counseling to patients with hemoglobinopathy and to their relatives. The authors emphasized that preventive programs using information-, education- and communication-based methods are feasible and allow for individuals to acquire knowledge of the consequences of hemoglobinopathies, the odds of transmitting them and the available options for family planning.

Thus, the key elements for the prevention of hemoglobinopathies are information, laboratory diagnosis and genetic counseling. In addition, genetic counseling should not be coercive but should enable the affected couples to make an informed decision and ensure their reproductive freedom(2525 Giordano PC. Prospective and retrospective primary prevention of hemoglobinopathies in multiethnic societies. Clin Biochem. 2009;42(18):1757-66).

The efficacy of the educational process might be centered on the identification of individuals with hemoglobinopathy through neonatal screening(2626 Hayeems RZ, Bytautas JP, Miller FA. A systematic review of the effects of disclosing carrier results generated through newborn screening. J Genet Couns. 2008;17(6):538-49) or any other diagnostic resource(2727 Amato A, Giordano PC. Screening and genetic diagnosis of hemoglobinopathies in Southern and Northern Europe: two examples. Mediterr J Hematol Infect Dis. 2009;1(1):e2009007) followed by the provision of information, which provides countless benefits to families, such as the possibility of future reproductive choices, awareness of the relevance of the status of individuals with this disease and the advancement of genetic knowledge. Most parents of children with sickle cell anemia who were provided genetic counseling increased and maintained their knowledge about the disease, particularly when counseling was performed by specialized services(2626 Hayeems RZ, Bytautas JP, Miller FA. A systematic review of the effects of disclosing carrier results generated through newborn screening. J Genet Couns. 2008;17(6):538-49).

Several proposals were observed in the present review, such as the selection of unaffected embryos for later implantation(1818 Farra C, Nassar AH, Usta IM, Salameh P, Souaid M, Awwad J. Acceptance of preimplantation genetic diagnosis for β-thalassemia in Lebanese women with previously affected children. Prenat Diagn. 2008;28(9):828-32), which is advocated as an option for the Palestinian community as a result of its high prevalence of β-thalassemia and religious restrictions. At-risk couples from that same area are also suggested not to conceive children(1919 Tazari I, Al Najjar E, Lulu N, Sirdah M. Obligatory premarital tests for β-thalassaemia in the Gaza Strip: evaluation and recommendations. Int J Lab Hematol. 2007;29(2):111-8).

It is worth noting that the investigators who conducted the three Brazilian studies included in the present review(1717 Souza RAV, Pratesi R, Fonseca SF. Programa de triagem neonatal para hemoglobinopatias em Dourados, MS: uma análise. Rev Bras Hematol Hemoter. 2010;32(2):126-30,2020 Diniz D, Guedes C. Confidencialidade, aconselhamento genético e saúde pública: um estudo de caso sobre o traço falciforme. Cad Saúde Pública. 2005;21(3):747-55,2222 Viana-Baracioli LMS, Bonini-Domingos CR, Pagliusi RA, Naoum PC. Prevenção de hemoglobinopatias a partir do estudo em gestantes. Rev Bras Hematol Hemoter. 2001;23(1):31-9) chose screening and genetic counseling services. This observation demonstrates that the educational process is an essential tool for the prevention of genetic diseases in Brazil, where abortion is prohibited.

Due to the high prevalence of hemoglobinopathies in Brazil and the need to provide genetic counseling, Ruling no. 1,391(2828 Brasil. Ministério da Saúde. Portaria n. 1.391, de 16 de agosto de 2005. Institui no âmbito do Sistema Único de Saúde, as diretrizes para a Política Nacional de Atenção Integral às Pessoas com Doença Falciforme e outras Hemoglobinopatias [Internet]. Brasília; 2005 [citado 2013 dez. 12]. Disponível em: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-1391.htm
http://dtr2001.saude.gov.br/sas/PORTARIA...
) from 2005 established the promotion of access to information and genetic counseling for families and individuals with sickle cell disease or traits within the framework of the Unified Health System (Sistema Único de Saúde - SUS). This type of encouragement policy might serve as a model of prevention for other countries in which therapeutic abortion is prohibited, as it is in Brazil.

Several actions aimed at controlling hemoglobinopathies might be incorporated into the public primary care setting. Among such actions, the following stand out: population and family screening, multidisciplinary and multi-professional follow up and access to services specialized in genetic counseling (1010 Ramalho AS, Magna LA. Aconselhamento genético do paciente com doença falciforme. Rev Bras Hematol Hemoter. 2007;29(3):229-32,1212 Guedes C, Diniz D. A ética na história do aconselhamento genético: um desafio à educação médica. Rev Bras Educ Med. 2009;33(2):247-52-1313 Guimarães CTL, Coelho GO. A importância do aconselhamento genético na anemia falciforme. Ciênc Saúde Coletiva. 2010;15 Supl.1:1733-40,2929 Bonini-Domingos CR. Programa de Triagem Neonatal de Hemoglobinopatias: uma reflexão [editorial]. Rev Bras Hematol Hemoter. 2010;32(2):99).

Although training and additional resources are needed, genetic counseling should be implemented in the public healthcare system as a program to ensure access to healthcare for individuals with hemoglobin disorders. The benefits are considerable, as genetic counseling decreases the morbidity and mortality and reduces the financial costs associated with this condition, improves the quality of life of patients, prevents complications and sequelae and helps all of the affected individuals to make informed decisions about their reproductive future.

Conclusion

The present systematic review showed that few individuals who are homozygous or heterozygous for hemoglobinopathies from several countries have been provided genetic counseling to date, although the implementation of preventive actions has paramount importance. Thus, these findings establish the need to implement a larger number of genetic counseling programs that do not encourage therapeutic abortion in an attempt to demonstrate that this type of intervention might help individuals affected by or homozygous for hemoglobinopathies to better understand aspects that are crucial for disease management and for family planning.

References

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    Cardoso GL, Guerreiro JF. Molecular characterization of sickle cell anemia in the Northern Brazilian State of Pará. Am J Hum Biol. 2010;22(5):573-7
  • 02
    Belisário AR, Viana MB. Efeitos da talassemia alfa nas manifestações clínicas e hematológicas da anemia falciforme: uma revisão sistemática. Rev Med Minas Gerais. 2010;20(1):312-21
  • 03
    Dias TL, Oliveira CGT, Enumo SRF, Paula KMO. A dor no cotidiano de cuidadores e crianças com anemia falciforme. Psicol USP. 2013;24(3):391-411
  • 04
    Santos MZ, Kusahara DM, Pedreira MLG. The experiences of intensive care nurses in the assessment and intervention of pain relief in children. Rev Esc Enferm USP. 2012;46(5):1074-81
  • 05
    Carvalho FS, Dias-Penna KGB, Araújo ES, Ramos ALM, Bataus LAM. Estudo comparativo da eficiência da eletroforese alcalina em acetato de celulose na identificação de hemoglobinas utilizando diferentes tampões. Rev Bras Anal Clin. 2010;42(4):293-6
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    Brasil. Ministério da Saúde. Portaria n. 55, de 29 de janeiro de 2010. Protocolo Clínico e Diretrizes Terapêuticas - Doença Falciforme [Internet]. Brasília; 2010 [citado 2013 dez. 12]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/sas/2010/prt0055_29_01_2010.html
    » http://bvsms.saude.gov.br/bvs/saudelegis/sas/2010/prt0055_29_01_2010.html
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    Fraser FC. Current issues in medical genetics. Am J Hum Genet. 1974;26(5):636-61
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    Resta R, Biesecker BB, Bennett RL, et al. A new definition of genetic counseling: National Society of Genetic Counselors’ Task Force Report. J Genet Couns. 2006;15(2):77-83
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    Ramalho AS, Magna LA. Aconselhamento genético do paciente com doença falciforme. Rev Bras Hematol Hemoter. 2007;29(3):229-32
  • 11
    Henshaw SK. Induced abortion: a world review. Fam Plann Perspect. 1990;22(2):76-89
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    Guedes C, Diniz D. A ética na história do aconselhamento genético: um desafio à educação médica. Rev Bras Educ Med. 2009;33(2):247-52
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    Guimarães CTL, Coelho GO. A importância do aconselhamento genético na anemia falciforme. Ciênc Saúde Coletiva. 2010;15 Supl.1:1733-40
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    Houwink EJF, Henneman L, Westerneng M, van Luijk SJ, Cornel MC, Dinant JG, et al. Prioritization of future genetics education for general practitioners: a Delphi study. Genet Med. 2012;14(3):323-29
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    Memish ZA, Saeedi MY. Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia. Ann Saudi Med. 2011;31(3):229-35
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    Kladny B, Williams A, Gupta A, Gettig EA, Krishnamurti L. Genetic counseling following the detection of hemoglobinopathy trait on the newborn screen is well received, improves knowledge, and relieves anxiety. Genet Med. 2011;13(7):658-61
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    Souza RAV, Pratesi R, Fonseca SF. Programa de triagem neonatal para hemoglobinopatias em Dourados, MS: uma análise. Rev Bras Hematol Hemoter. 2010;32(2):126-30
  • 18
    Farra C, Nassar AH, Usta IM, Salameh P, Souaid M, Awwad J. Acceptance of preimplantation genetic diagnosis for β-thalassemia in Lebanese women with previously affected children. Prenat Diagn. 2008;28(9):828-32
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    Tazari I, Al Najjar E, Lulu N, Sirdah M. Obligatory premarital tests for β-thalassaemia in the Gaza Strip: evaluation and recommendations. Int J Lab Hematol. 2007;29(2):111-8
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    Diniz D, Guedes C. Confidencialidade, aconselhamento genético e saúde pública: um estudo de caso sobre o traço falciforme. Cad Saúde Pública. 2005;21(3):747-55
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    Karetti M, Yardumian A, Karetti D, Modell B. Informing carriers of β-thalassemia: giving the good news. Genet Test. 2004;8(2):109-13
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    Viana-Baracioli LMS, Bonini-Domingos CR, Pagliusi RA, Naoum PC. Prevenção de hemoglobinopatias a partir do estudo em gestantes. Rev Bras Hematol Hemoter. 2001;23(1):31-9
  • 23
    Pina-Neto JM. Aconselhamento genético. J Pediatr. 2008;84(4 Supl.):S20-6
  • 24
    Elwyn G, Gray J, Clarke A. Shared decision making and non-directiveness in genetic counselling. J Med Genet. 2000;37(2):135-8
  • 25
    Giordano PC. Prospective and retrospective primary prevention of hemoglobinopathies in multiethnic societies. Clin Biochem. 2009;42(18):1757-66
  • 26
    Hayeems RZ, Bytautas JP, Miller FA. A systematic review of the effects of disclosing carrier results generated through newborn screening. J Genet Couns. 2008;17(6):538-49
  • 27
    Amato A, Giordano PC. Screening and genetic diagnosis of hemoglobinopathies in Southern and Northern Europe: two examples. Mediterr J Hematol Infect Dis. 2009;1(1):e2009007
  • 28
    Brasil. Ministério da Saúde. Portaria n. 1.391, de 16 de agosto de 2005. Institui no âmbito do Sistema Único de Saúde, as diretrizes para a Política Nacional de Atenção Integral às Pessoas com Doença Falciforme e outras Hemoglobinopatias [Internet]. Brasília; 2005 [citado 2013 dez. 12]. Disponível em: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-1391.htm
    » http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-1391.htm
  • 29
    Bonini-Domingos CR. Programa de Triagem Neonatal de Hemoglobinopatias: uma reflexão [editorial]. Rev Bras Hematol Hemoter. 2010;32(2):99

Publication Dates

  • Publication in this collection
    Oct 2014

History

  • Received
    05 Feb 2014
  • Accepted
    21 Aug 2014
Universidade de São Paulo, Escola de Enfermagem Av. Dr. Enéas de Carvalho Aguiar, 419 , 05403-000 São Paulo - SP/ Brasil, Tel./Fax: (55 11) 3061-7553, - São Paulo - SP - Brazil
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