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Incidence and risk factors for agranulocytosis in Latin American countries—the Latin Study

A multicenter study

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

LATIN is a multinational case–control study designed to identify risk factors for agranulocytosis and to estimate the incidence rate of the disease in some Latin American countries.

Methods

Each study site in Brazil, Argentina and Mexico conducted an active search of agranulocytosis patients in hematology clinics and looked for possible associations with drug use.

Results

The overall incidence rate was 0.38 cases per 1 million inhabitant–years. Agranulocytosis patients more often took medications already associated with agranulocytosis than controls (p = 0.01), mainly methimazole (OR 44.2, 95% CI 6.8 to infinity). The population attributable risk percentage (etiologic fraction) was 56%. The use of nutrient supplements was more frequent among patients than controls (p = 0.03).

Conclusions

Agranulocytosis seems to be very rare in Latin America. The lower than expected number of cases identified during the study period precluded estimation of the risk associated to individual drugs, with the exception of methimazol. However, this is the longest series of agranulocytosis cases ever gathered in Latin America, and information on drug exposures was collected prospectively. The conclusion is that drug-induced agranulocytosis does not seem to be a major public health problem in the study regions.

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References

  1. Ibáñez L, Vidal X, Ballarín E, Laporte JR (2005) Population-based drug-induced agranulocytosis. Arch Intern Med 165(8):869–874

    Article  PubMed  Google Scholar 

  2. Young NS (1994) Agranulocytosis. JAMA 271(12):935–938

    Article  PubMed  CAS  Google Scholar 

  3. Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA 256(13):1749–1757

  4. Hamerschlak N, Cavalcanti AB (2005) Neutropenia, agranulocytosis and dipyrone. Sao Paulo Med J 123(5):247–249

    Article  PubMed  Google Scholar 

  5. Kaufman DW, Kelly JP, Jurgelon JM et al (1996) Drugs in the aetiology of agranulocytosis and aplastic anaemia. Eur J Haematol Suppl 60:23–30

    PubMed  CAS  Google Scholar 

  6. Kaufman DW, Kelly JP, Levy M, Shapiro S (1991) The drug etiology of agranulocytosis and aplastic anemia: the international agranulocytosis and aplastic anemia study. New York, Oxford University Press

    Google Scholar 

  7. Andersohn F, Konzen C, Garbe E (2007) Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 146(9):657–665

    PubMed  Google Scholar 

  8. Ibáñez L, Vidal X, Ballarín E, Laporte JR (2005) Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol 60(11):821–829

    Article  PubMed  Google Scholar 

  9. Shapiro S, Issaragrisil S, Kaufman DW et al (1999) Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group. Am J Trop Med Hyg 60(4):573–577

    PubMed  CAS  Google Scholar 

  10. Hamerschlak N, Montezuma MP, Bacal N et al (1993) Retrospective prevalence and incidence of drug-induced agranulocytosis in the city of São Paulo-Brazil. Rev Paul Med 111(1):294–298

    PubMed  CAS  Google Scholar 

  11. Hamerschlak N, Maluf E, Pasquini R et al (2005) Incidence of aplastic anemia and agranulocytosis in Latin America–the LATIN study. Sao Paulo Med J 123(3):101–104

    Article  PubMed  Google Scholar 

  12. Hennekens CH, Buring JE (1987) Measures of disease frequency. In: Hennekens CH, Buring E (eds) Epidemiology in medicine. Lippincott, Williams & Wilkins, Philadelphia

  13. Hine LK, Gerstman BB, Wise RP, Tsong Y (1990) Mortality resulting from blood dyscrasias in the United States, 1984. Am J Med 88(2):151–153

    Article  PubMed  CAS  Google Scholar 

  14. Böttiger LE, Furhoff AK, Holmberg L (1979) Drug-induced blood dyscrasias. A ten-year material from the Swedish Adverse Drug Reaction Committee. Acta Med Scand 205(6):457–461

    PubMed  Google Scholar 

  15. Arneborn P, Palmblad J (1979) Drug-induced neutropenias in the Stockholm region 1976–1977. Acta Med Scand 206(4):241–243

    PubMed  CAS  Google Scholar 

  16. Arneborn P, Palmblad J (1982) Drug-induced neutropenia–a survey for Stockholm 1973–1978. Acta Med Scand 212(5):289–292

    PubMed  CAS  Google Scholar 

  17. Tavassoli N, Duchayne E, Sadaba B et al (2007) Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals. Eur J Clin Pharmacol 63(3):221–228

    Article  PubMed  CAS  Google Scholar 

  18. Andrès E, Zimmer J, Affenberger S et al (2006) Idiosyncratic drug-induced agranulocytosis: Update of an old disorder. Eur J Intern Med 17(8):529–535

    Article  PubMed  Google Scholar 

  19. Benseñor IM (2005) Dipyrone and blood dyscrasia revisited: “non-evidence based medicine”. Sao Paulo Med J 123(3):99–100

    Article  PubMed  Google Scholar 

  20. Garcia S, Canionero M, Lopes G (2006) Dipyrone-induced granulocytopenia: a case for awareness. Pharmacotherapy 26(3):440–442

    Article  PubMed  Google Scholar 

  21. Hedenmalm K, Spigset O (2002) Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol 58(4):265–274

    Article  PubMed  CAS  Google Scholar 

  22. Carvalho-Silva DR, Santos FR, Rocha J, Pena SD (2001) The phylogeography of Brazilian Y-chromosome lineages. Am J Hum Genet 68(1):281–286

    Google Scholar 

  23. Dettling M, Cascorbi I, Opgen-Rhein C, Schaub R (2007) Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. Pharmacogenomics J 7(5):325–332

    Article  PubMed  CAS  Google Scholar 

  24. Güzelcan Y, Scholte WF (2006) Door clozapine geïnduceerde agranulocytose: genetische en immunologische verklaringen. [Clozapine-induced agranulocytosis: genetic risk factors and an immunologic explanatory model]. Tijdschr Psychiatr 48(4):295–302

    PubMed  Google Scholar 

  25. World Health Organization (2006) WHO Statistical Information System (WHOSIS). Core Health Indicators. World Health Organization. http://www.who.int/whosis/database/core/core_select.cfm. Accessed 15 Feb 2007

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Acknowledgments

The authors want to thank Joan Laporte and David Kaufman for the careful review of the text.

Disclosure

This study was supported by a grant from Sanofi Aventis and Boehringer Ingelheim. The study sponsors were not involved at all in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and had the ultimate responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. 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

    Nelson Hamerschlak, Alexandre Biasi Cavalcanti & Álvaro Avezum Júnior

  2. Hospital das Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Eliane Maluf & Ricardo Pasquini

  3. Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil

    José Eluf-Neto

  4. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

    Roberto Passeto Falcão & Maria Carolina Tostes Pintão

  5. Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil

    Irene Gyongyvér Heidemarie Lorand-Metze

  6. Policlínica Bancaria, Obra Social Bancaria Argentina, Buenos Aires, Argentina

    Daniel Goldenberg

  7. Instituto de Hemoterapia de Goiânia, Goiânia, GO, Brazil

    Cézar Leite Santana

  8. Hemocentro Regional de Juiz de Fora, Juiz de Fora, MG, Brazil

    Daniela de Oliveira Werneck Rodrigues

  9. Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil

    Leny Nascimento da Motta Passos

  10. Fundação Hemope, Recife, PE, Brazil

    Erika Oliveira de Miranda Coelho

  11. Hemocentro Regional de Uberaba, Uberaba, MG, Brazil

    Hélio Moraes de Souza

  12. Hospital San José Tec de Monterrey, Monterrey, México

    José Rafael Borbolla

Authors
  1. Nelson Hamerschlak
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  2. Eliane Maluf
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  3. Alexandre Biasi Cavalcanti
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  4. Álvaro Avezum Júnior
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  5. José Eluf-Neto
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  6. Roberto Passeto Falcão
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  7. Irene Gyongyvér Heidemarie Lorand-Metze
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  8. Daniel Goldenberg
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  9. Cézar Leite Santana
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  10. Daniela de Oliveira Werneck Rodrigues
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  11. Leny Nascimento da Motta Passos
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  12. Erika Oliveira de Miranda Coelho
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  13. Maria Carolina Tostes Pintão
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  14. Hélio Moraes de Souza
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  15. José Rafael Borbolla
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  16. Ricardo Pasquini
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Corresponding author

Correspondence to Nelson Hamerschlak.

Additional information

Investigators in the LATIN Study

Steering Committee: Nelson Hamerschlak, Ricardo Pasquini, Eliane Maluf, José Eluf Neto, Álvaro Avezum.

Executive Committee: Álvaro Avezum, Iria R. Okano, Fernanda de Oliveira Alves Lima, Luis Paulo Agostino de Magalhães Duprat, Alexandre Biasi Cavalcanti.

Independent Validation Committee: Marimília T. Pita, Roberto Passeto Falcão,

Luís G. Rosenfeld, Sandra R. Loggetto, Irene G. H. L. Metze, Andreza Alice Feitosa Ribeiro, Morgani Rodrigues, Elvira Deolinda Velloso

Data Management: Ruy Guilherme Rodrigues Cal, Marcos Rodrigues Gouveia

Statistician: Frederico R. Moreira

Advisory Board: David Kaufman, Samuel Shapiro, Joan R. Laporte, Ricardo Sesso,

Celso Guerra

Investigators:

Brazil: Hospital da Clínicas da Universidade Federal do Paraná, Curitiba: Eliane Maluf, Ricardo Pasquini, Maria Inês Neves, Solange Delazeri; Instituto de Hemoterapia de Goiânia, Goiânia: César. L. Sant’Anna, Geraldo S. Cunha Jr., Luciana S. Cunha Jr; Hemocentro Regional de Juiz de Fora, Juiz de Fora: Daniela W. Rodrigues, Abrahão Hallak Neto, Camila S. Hallak; Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus: Leny M. Passos, Suênia Araujo, Lana Sulamita dos Santos Vecchia, Maria de Nazaré Faunier Barboza, Rosangela Castro; Fundação Hemope, Recife: Erika O. Coelho, Raul Melo, Maria F. Patú; Waldelourdes Souto Maior; Faculdade de Medicina da Universidade de São Paulo (FMUSP) Campus Ribeirão Preto, Ribeirão Preto: Rodrigo Calado de Rodrigues, Maria Carolina R Pintão, Daniel Mazza; Hemocentro Regional de Uberaba, Uberaba: Hélio M. de Souza, Ana Marcela R. Fosnseca, Gisele M. P. Sternick. Argentina: Hospital de Clínicas José de San Martín, Buenos Aires: Daniel Goldenberg (Buenos Aires Study Coordinator), Ariel Goldenberg; Hospital Francés, Buenos Aires: María Pía Amoroso Copello; Policlínica Bancaria, Buenos Aires: Carlos Marín; Hospital de Niños “Ricardo Gutierrez”, Buenos Aires: Raúl Plager, Guillermo Drelichman; Hospital Alvarez, Buenos Aires: Fernando Bezares; Hospital Churruca, Buenos Aires: Luis Palmer, Graciela Schwalb; Swiss Medical Group, Buenos Aires: Hugo Ferro; Hospital Italiano, Buenos Aires: Dorotea Fantl, María Paula Cárdenas. Mexico: Hospital San José Tec de Monterrey, Monterrey: José Rafael Borbolla, Nancy G. Maldonado.

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Hamerschlak, N., Maluf, E., Biasi Cavalcanti, A. et al. Incidence and risk factors for agranulocytosis in Latin American countries—the Latin Study. Eur J Clin Pharmacol 64, 921–929 (2008). https://doi.org/10.1007/s00228-008-0513-7

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  • DOI: https://doi.org/10.1007/s00228-008-0513-7

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