Aplastic anemia in Brazil: Incidence and risk factors

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Aplastic Anemia in Brazil: Incidence and Risk Factors. Eliane M.C.P. Maluf,1* Ricardo Pasquini,1 Jose N. Eluf,2 Judith Kelly,3 and David W. Kaufman3.
American Journal of Hematology 71:268–274 (2002)

Aplastic Anemia in Brazil: Incidence and Risk Factors Eliane M.C.P. Maluf,1* Ricardo Pasquini,1 Jose N. Eluf,2 Judith Kelly,3 and David W. Kaufman3 1

Bone Marrow Transplantation Center, Faculty of Medicine, Federal University of Parana, Curitiba, Brazil 2 Preventive Medicine Department, Faculty of Medicine, Sa˜o Paulo University, Sa˜o Paulo, Brazil 3 Slone Epidemiology Center, Boston University School of Medicine, Boston, Massachusetts

This study is the first large-scale epidemiological investigation of acquired aplastic anemia (AAA) in South America. The objective was to estimate the incidence and to identify risk factors for AAA in Brazil. A national case–control study was conducted to investigate the risk factors for the disease. One hundred twenty-five cases and 129 controls were included. Multiple logistic regression was used in the estimation of odds ratios (OR) to control confounding. The size of Brazil made it unfeasible to estimate the incidence of AAA in the whole country, and we limited the calculation to the state of Parana. The annual incidence of AAA in Parana was 2.4 cases/106 inhabitants. There was no positive association between chloramphenicol use and AAA (OR 0.4; 95% CI: 0.1–2.9). The OR of AAA associated with household pesticides that include organophosphates in their composition was 2.7 (1.0–8.4). The OR for the usage of unspecified thinner and/or acetone for at least 7 days was 3.0 (1.2–7.3). Cases of AAA in Brazil seem to be associated with some factors traditionally related to this disease, such as certain solvents and the incidence is similar to what has been reported from Europe. Am. J. Hematol. 71:268–274, 2002. © 2002 Wiley-Liss, Inc.

Key words: aplastic anemia; epidemiology; incidence; etiology; risk factors; Brazil

INTRODUCTION

Acquired aplastic anemia (AAA) is a rare hematological disease with a high lethality rate, often of unknown origin [1,2]. The incidence seems to vary geographically. The annual incidence rate reported in the literature ranges from 1.4 to 14 cases per million with the range from more rigorous studies from 1.4 to 3.7 [3]. AAA occurs more frequently in the Orient than in Western countries [3]. It is believed that environmental factors are more important than genetic factors to explain this difference [4,5]. The determination of risk factors for AAA faces multiple difficulties. The evidence of the myelotoxicity of several drugs, infectious agents, solvents, and other chemical agents is circumstantial; there are no tests available that could confirm their cause-effect relationship. In addition, multiple exposures are the rule. It is very difficult or even impossible to isolate the offending agent of the bone marrow. For these reasons from 50 to 74 percent of AAA cases in the literature are classified as idiopathic [2,6]. The present study was the first large-scale epidemiological investigation of the disease in South America. © 2002 Wiley-Liss, Inc.

The goals were to identify risk factors for AAA in Brazil and to estimate the incidence rate of AAA in the state of Parana. MATERIALS AND METHODS

The study was performed in the Bone Marrow Transplantation Center, at the Hospital de Clinicas—Curitiba, Universidade Federal do Parana (UFPR), state of Parana, in southern Brazil. This service is a national referral center for the treatment of AAA patients in Brazil, and receives cases from all regions of the country. Incidence Study

The size of Brazil makes it unfeasible to estimate the incidence of AAA in the whole country. We limited the *Correspondence to: Eliane M.C.P. Maluf, M.D., Department of Internal Medicine, Faculty of Medicine, Hospital de Clinicas, Federal University of Parana, Av. Silva Jardim 2833, Apto. 501, Cep 80240020, Curitiba, PR, Brazil. E-mail: [email protected] Received for publication 9 January 2002; Accepted 15 August 2002 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ajh.10232

Aplastic Anemia in Brazil: Incidence and Risk Factors

calculation to the state of Parana, for which ascertainment of cases was judged to be complete. All cases of AAA diagnosed between 1997 and 1998 were identified prospectively. We obtained a list of all hematologists of the state of Parana from the Regional Medicine Council. The main researcher called each one to explain the importance of the study. After this, a formal document was sent to all of the referred hematologists from the cities of the state of Parana. All the hematologists returned the form with the required information. We received information about age, sex, diagnosis, and patient’s residence. All patients had been submitted to peripheral blood count, bone marrow aspiration, and/or bone marrow biopsy. All patients under 18 years old had been submitted to specific test to exclude Fanconi’s anemia. Census data was used to estimate the incidence. The population of Parana was 9.34 million (1996 official census). Patients included in this study had at least two of the following three peripheral blood count criteria: granulocytes < 1,000/mm3; platelets < 20,000/mm3; reticulocytes < 1%, in presence of anemia. To exclude alternative diagnoses, the final acceptance of cases for inclusion in the study required a characteristic hypocellular bone marrow biopsy (marrow cellularity