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Serum ferritin levels in beta thalassemia carrier

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Abstract

A low iron level, the commonest nutritional deficiency in the world, is a public health problem in developing countries. On the other hand, an excessive amount of iron is toxic, causing several organic dysfunctions, such as diabetes, cirrhosis, endocrinopathies and heart disease. Researchers have reported an association of iron overload with beta-thalassemia. The aim of this paper was to compare the serum ferritin levels of women with the beta-thalassemia trait. The results of serologic tests of 137 women of childbearing age were analyzed; 63 had the beta-thalassemia trait and 74 had Hb AA. In the beta-thalassemia carriers, the median ferritin value was 51.90 ng/mL and in the non-carriers 31.60 ng/mL (p = 0.0052). Levels of less than 20 and above 150 ng/mL were observed in 28% and 3% of the non-carriers and in 16% and 11% of the carriers, respectively. With these results it is possible to conclude that women in the reproductive age with the beta-thalassemia trait present higher ferritin levels in the northeastern region of São Paulo State. Further studies are necessary to clarify possible genetic and/or environment factors which interfere in iron absorption.
171
Carta ao Editor / Letter to Editor
Valores de ferritina sérica em beta
talassemia heterozigota
Serum ferritin levels in beta thalassemia
carrier
REVISTA BRASILEIRA
DE HEMATOLOGIA
E HEMOTERAPIA
REVISTA BRASILEIRA
DE HEMATOLOGIA
E HEMOTERAPIA
Sr. Editor
Estima-se que 1,5% a 3% da população mundial sejam
portadores do traço talassêmico.1 No Brasil, a incidência
depende da região avaliada. No estado de São Paulo acredita-
se que 2% dos indivíduos sejam portadores dessa alteração
de hemoglobinas.2
Os heterozigotos geralmente são assintomáticos e o
quadro hematológico se caracteriza por diminuição dos níveis
de hemoglobina (Hb), redução do volume corpuscular médio
(VCM), sendo frequentemente confundida com anemia ferro-
priva. O diagnóstico diferencial é realizado pela avaliação
dos índices hematológicos, análise morfológica do sangue
periférico e quantificação das Hb A2 e Hb Fetal.3 A avaliação
da ferritina sérica é fundamental para a discriminação diag-
nóstica.
Os níveis de ferro podem ser influenciados pelo aumen-
to na absorção, pela baixa excreção e por mecanismos que
regulem esse processo.4,5,6 A deficiência está relacionada a
estados mórbidos, como alterações neurológicas, complica-
ções obstétricas e do recém-nascido, incapacidade para o
trabalho e imunodeficiência.5,6,7 Os grupos mais suscetíveis
são as crianças entre 1 e 3 anos de
idade, adolescentes, mulheres em
idade fértil e idosos.8,9
Com o objetivo de comparar os
níveis de ferritina sérica entre mulhe-
res portadoras e não portadoras de
beta talassemia heterozigota, avali-
amos 137 mulheres no período de um
ano, 63 com diagnóstico de beta-
talassemia heterozigota e 74 com
1Médica hematologista. Preceptora de Clínica médica da UFSCar
2Biomédica do Laboratório Unilab, São Carlos-SP
3Professor. Departamento de Ciências da Computação e Estatística -
Unesp, Campus de São José do Rio Preto-SP
4Bióloga. Professora do Depto. de Biologia, Unesp, São José do Rio
Preto-SP
Isabeth F. Estevão1
Maria Cristina S. Souza2
Antonio J. Manzato3
Claudia R. Bonini-Domingos4
hemoglobinas normais (Hb AA). Esse foi um estudo
retrospectivo, fundamentado em observação clínica de que
portadoras de beta talassemia heterozigota apresentavam
valores de ferritina aumentados. A seleção das mulheres foi
aleatória e segundo a sua busca por consulta médica. Nesse
momento foram orientadas sobre a pesquisa e, após o con-
sentimento, incluídas no estudo. Os critérios de inclusão
no grupo das não portadoras foram o nível de Hb igual ou
superior a 12g/dL e o VCM entre 80 e 100 pg, e os de exclu-
são, para ambos os grupos, o uso de medicamentos à base
de ferro há pelo menos um mês e a presença de doenças
inflamatórias e/ou neoplásicas. As idades encontravam-se
entre 10 e 49 anos.
O diagnóstico de beta talassemia foi baseado em hemo-
grama (Pentras 120 Retic-Horiba ABX), na quantificação das
Hb A2 e Hb Fetal por HPLC (Bio-Rad) e na análise morfo-
lógica de sangue periférico. A dosagem de ferritina sérica foi
realizada por quimioluminescência e esses resultados anali-
sados estatisticamente pelo teste de Mann Whitney.
No grupo de mulheres não portadoras de talassemia
beta minor, a idade variou de 10 a 48 anos, com média de 31,5
anos, e entre as portadoras de talassemia, de 12 a 49 anos,
com média de 28, 48 anos. Os valores de Hb e VCM, utilizados
para a separação dos grupos, estão descritos na Tabela 1 e
evidenciam as diferenças inerentes à beta talassemia hetero-
zigota.
O valor de ferritina sérica variou de 5,00 a 489,49 ng/ml
com mediana de 51,90 nas portadoras de beta talassemia e de
7,09 a 170,00 ng/mL com mediana de 31,60 nas não portadoras.
Valores acima de 150 ng/mL foram observados em sete (11%)
mulheres com talassemia e, em apenas duas (3%) do grupo
com Hb AA, encaminhadas para avaliação de hemocro-
matose. Em 10 (16%) talassêmicas e em 20 (27%) não talassê-
micas foram encontrados valores abaixo de 20 ng/ml indicando
deficiência de ferro, posteriormente investigada. A avaliação
estatística dos níveis globais de ferritina sérica mostrou
diferença significante entre os dois grupos (p = 0,0052)
conforme ilustra a Figura 1.
Na beta talassemia heterozigota, geralmente a eritro-
cinética é normal, podendo ocorrer discreta diminuição da
sobrevida dos eritrócitos e leve eritropoese ineficaz. Todavia,
alguns estudos têm demonstrado a presença de sobrecarga
de ferro nesses pacientes.10,11,12 A fisiopatologia dessa asso-
ciação não está esclarecida e sugere-se um sinergismo entre
as mutações nos genes que codificam proteínas relacionadas
à absorção de ferro e a beta talassemia.11,12 A diferença de
ferritina entre os dois grupos estudados sugere maior poder
172
Carta ao Editor Rev. Bras. Hematol. Hemoter. 2010;32(2):171-172
de absorção do ferro intestinal em portadoras de beta talas-
semia heterozigota. Em algumas situações, como em gestan-
tes, crianças, adolescentes e mulheres que menstruam, podem
acarretar uma vantagem seletiva.12 Por outro lado, quando
não existe aumento das necessidades de absorção, há o risco
do desenvolvimento de sobrecarga e, eventualmente, dano
orgânico.
A heterogeneidade dos valores encontrados e a não
correlação com os níveis de hemoglobina sugerem que esse
aumento da absorção possa ser não só pela hemólise e eritro-
poese ineficaz desencadeada pela talassemia. Portanto, há
necessidade de investigação de possíveis fatores genéticos
e/ou ambientais que possam influenciar o mecanismo de
absorção em talassêmicos do tipo beta heterozigotos.
Abstract
A low iron level, the commonest nutritional deficiency in the world,
is a public health problem in developing countries. On the other
hand, an excessive amount of iron is toxic, causing several organic
dysfunctions, such as diabetes, cirrhosis, endocrinopathies and
heart disease. Researchers have reported an association of iron
overload with beta-thalassemia. The aim of this paper was to
compare the serum ferritin levels of women with the beta-
thalassemia trait. The results of serologic tests of 137 women of
childbearing age were analyzed; 63 had the beta-thalassemia trait
and 74 had Hb AA. In the beta-thalassemia carriers, the median
ferritin value was 51.90 ng/mL and in the non-carriers 31.60 ng/mL
(p = 0.0052). Levels of less than 20 and above 150 ng/mL were
observed in 28% and 3% of the non-carriers and in 16% and 11% of
the carriers, respectively. With these results it is possible to conclude
that women in the reproductive age with the beta-thalassemia trait
present higher ferritin levels in the northeastern region of São Paulo
State. Further studies are necessary to clarify possible genetic and/
or environment factors which interfere in iron absorption. Rev.
Bras. Hematol. Hemoter. 2010;32(2):171-172.
Key words: Beta-thalassemia; ferritins; iron deficiency.
Referências Bibliográficas
1. Galanello R, et al. Prevention of thalassaemias and other
haemoglobin disorders. Nicosia: Thalassaemia International
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2. Cançado RD, Jesus JA. A doença falciforme no Brasil. Rev Bras
Hematol Hemoter. 2007;29(3):203-6.
3. Clark BE, Thein SL. Molecular diagnosis of haemoglobin disorders.
Clin Lab Haematol. 2004;26(3):159-76.
4. Andrews NC. Molecular control of iron metabolism. Best Pract
Res Clin Haematol. 2005;18(2):159-69.
5. Ganz T, Nemeth E. Iron imports. VI. Hepcidin and regulation of
body iron metabolism. Am J Physiol Gastrointest Liver Physiol.
2006;290(2):G199-203
6. Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys
Acta. 2006;1763(7):700-10.
7. Booth IW, Aukett MA. Iron deficiency in infancy and early
childhood. Arch Dis Child. 1997;76(6):549-54.
8. De Maeyer EM. Preventing and controlling iron deficiency in
infancy anaemia through primary health care. Geneva: WHO;
1989.
9. Hallberg L, et al. Screening for iron deficiency; an analysis base on
bone marrow examinations and serum ferritin determinations in a
population sample of women. Br J Haematol. 1993;85(4):787-98.
10. Melis MA, Cau M, Deidda F, Barella S, Cao A, Galanello R. H63D
mutation in the HFE gene increases iron overload in beta-
thalassemia carriers. Haematologica. 2002;87(3):242-5.
11. Riva A, Mariani R, Bovo G, Pelucchi S, Arosio C, et al. Type 3
hemochromatosis and beta-thalassemia trait. Eur J Haematol.
2004;72(5):370-4.
12. Martins R, Picanço I, Fonseca A, Ferreira L, Rodrigues O, Coelho
M, et al. The role of HFE mutations on iron metabolism in beta-
thalassemia carriers. J Hum Genet. 2004;49(12):651-5.
Avaliação: Editor e dois revisores externos
Conflito de interesse: sem conflito de interesse
Recebido: 26/10/2009
Aceito após modificações: 01/02/2010
Unesp – Campus de São José do Rio Preto. Departamento de Biologia,
Laboratório de Hemoglobinas e Genética das Doenças Hematológicas
Correspondência: Isabeth da Fonseca Estevão
Laboratório de Hemoglobinas e Genética das Doenças Hematológicas,
Departamento de Biologia
Rua Cristóvão Colombo, 2265 – Jd Nazareth
15054-000 – Unesp – Campus de São José do Rio Preto-SP – Brasil
Tel.:/Fax (55 17)3221-2392.
E-mail: isabeth@terra.com.br
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