Haematologica, Vol 94, Issue 9, 1220-1226 doi:10.3324/haematol.2008.002642
Copyright © 2009 by Ferrata Storti Foundation
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Bone Marrow Failure

Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

Eliane Maluf2, Nelson Hamerschlak1, Alexandre Biasi Cavalcanti1, Álvaro Avezum Júnior1, José Eluf-Neto3, Roberto Passetto Falcão4, Irene G. Lorand-Metze5, Daniel Goldenberg6, Cézar Leite Santana7, Daniela de Oliveira Werneck Rodrigues8, Leny Nascimento da Motta Passos9, Luis Gastão Mange Rosenfeld1, Marimilia Pitta, Sandra Loggetto, Andreza A. Feitosa Ribeiro1, Elvira Deolinda Velloso1, Andrea Tiemi Kondo1, Erika Oliveira de Miranda Coelho10, Maria Carolina Tostes Pintão4, Hélio Moraes de Souza11, José Rafael Borbolla12, Ricardo Pasquini2

1 Hospital Israelita Albert Einstein/Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, Brazil
2 Hospital das Clínicas da Universidade Federal do Paraná, Curitiba, Brazil
3 Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
4 Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, Brazil
5 Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Campinas, Brazil
6 Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
7 Instituto de Hemoterapia de Goiânia, Goiânia, Brazil
8 Hemocentro Regional de Juiz de Fora, Juiz de Fora, Brazil
9 Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus (AM), Brazil
10 Fundação Hemope, Recife, Brazil
11 Hemocentro Regional de Uberaba, Uberaba, Brazil
12 Hospital San José Tec de Monterrey, Monterrey, México, Centro de Hematologia de São Paulo

Correspondence: Nelson Hamerschlak, Centro de Pesquisa Clínica, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Av. Albert Einstein, 627/701, Piso Chinuch, São Paulo (SP), Brazil, CEP 05651-901. E-mail:hamer{at}einstein.br

Background: Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained.

Design and Methods: This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis.

Results: The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (≥30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82–9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87–87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14–108.02).

Conclusions: The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone.

Key words: aplastic anemia, incidence, risk factors, benzene.