Thai Studies of Aplastic Anemia and Agranulocytosis

Objectives

To document the incidence of the two blood dyscrasias in Thailand, and to identify risk factors. It is thought that the incidence of aplastic anemia is higher than in Western countries, which suggests the possibility of a unique etiology. Factors of particular interest include pesticides, other environmental exposures, and hepatitis viruses, as well as drugs.

Methods

The study is of a population-based case-control design, with methods similar to the IAAAS. All cases of the dyscrasias meeting specified criteria that occur in three regions of Thailand , Bangkok , Khonkaen in the northeast, and Songkla in the south, (total population, 21.4 million) were identified, and interviewed if possible. Up to four hospital controls were matched to each interviewed case according to age, sex, and region. The study ended in Songkla in December 1994; and in Bangkok and Khonkaen in June 2002, with 541 cases of aplastic anemia, 36 cases of agranulocytosis, and 2261 hospital controls enrolled.

The information obtained included demographic details, medical history, current occupation and exposure to chemicals and other occupational factors, and detailed histories of pesticide and medication use in the six months before hospital admission. In addition, for as many cases as possible and at least one control per case, blood samples were obtained and tested for infection with hepatitis A, B, and C. Samples are also stored for the evaluation of future hypotheses.

The study is the largest epidemiologic investigation of aplastic anemia that has been conducted. Publications to date have shown an incidence in Bangkok that is approximately double that in Western countries, a strong inverse association between aplastic anemia and socioeconomic status, a low drug attributability, the relative safety of household pesticides, a strong association with grain farming in rural Thailand and an association with agricultural pesticides, and the relation of the disease to hepatitis viruses. Analyses of the full dataset are now in progress.

Investigators and Study Staff

David Kaufman, Sc.D., Co-Principal Investigator
Surapol Issaragrisil, M.D., Co-Principal Investigator
Kanchana Chansung, M.D., Co-Investigator
Tharatorn Thamprasit, M.D., Co-Investigator
Anon Piankijagum, M.D., Co-Investigator
Samuel Shapiro, M.B., F.R.C.P.(E), Co-Investigator
Neal S. Young, M.D., Co-Investigator
Paul E. Leaverton, Ph.D., Co-Investigator

Study Details

Sources of Funding:

  • National Heart, Lung, and Blood Institute
  • Hoechst AG
  • Grants in Thailand

Study Period:

January 1989 to February 2004

Publications

  • Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS, and the Aplastic Anemia Study Group. The epidemiology of aplastic anemia in Thailand. Blood 2006;107(4):1299-307.
  • Kaufman DW, Kelly JP, Issaragrisil S, Laporte JR, Anderson T, Levy M, Shapiro S, Young NS. Relative incidence of agranulocytosis and aplastic anemia. Am J Hematol 2006;81(1):65-7.
  • Issaragrisil S, Leaverton PE, Chansung K, Thamprasit T, Porapakham Y, Vannasaeng S, Piankijagum A, Kaufman DW, Anderson TE, Shapiro S, Young NS, and the Aplastic Anemia Study Group. Regional patterns in the incidence of aplastic anemia in Thailand. Am J Hematol 1999;61:164-8.
  • Shapiro S, Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakkham Y, Vannasaeng S, Leaverton PE, Young NS, and the Aplastic Anemia Study Group. Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Am J Trop Med Hyg 1999;60:573-7.
  • Wiholm BE, Kelly JP, Kaufman DW, Issaragrisil S, Levy M, Anderson T, Shapiro S. Relation of aplastic anaemia to use of chloramphenicol eye drops in two international case-control studies. BMJ 1998;316:666.
  • Werler MM. Teratogen update: smoking and reproductive outcomes. Teratology 1997;55:382-8.
  • Issaragrisil S, Kaufman DW, Thongput A, Chansung K, Thamprasit T, Piankijagum A, Anderson TE, Shapiro S, Leaverton PE, Young NS. Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand. Hepatology 1997;25:1255-7.
  • Kaufman DW, Issaragrisil S, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakkham Y, Vannasaeng S, Leaverton PE, Shapiro S, Young NS, and the Aplastic Anemia Study Group. Use of household pesticides and the risk of aplastic anaemia in Thailand. Int J Epidemiol 1997;26:643-50.
  • Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakkham Y, Vannasaeng S, Leaverton PE, Shapiro S, Young NS, and the Aplastic Anemia Study Group. Low drug attributability of aplastic anemia in Thailand. Blood 1997;89:4034-9.
  • Issaragrisil S, Kaufman DW, Anderson T, and the Aplastic Anemia Study Group. Incidence and non-drug aetiologies of aplastic anaemia in Thailand. Eur J Haematol 1996;57(Suppl.):31-4.
  • Kelly JP, Jurgelon JM, Issaragrisil S, Keisu M, Kaufman DW. An epidemiological study of aplastic anaemia: relationship of drug exposures to clinical features and outcome. Eur J Haematol 1996;57(Suppl.):47-52.
  • Kaufman DW, Kelly JP, Jurgelon JM, Anderson T, Issaragrisil S, Wiholm BE, Young NS, Leaverton P, Levy M, Shapiro S. Drugs in the aetiology of agranulocytosis and aplastic anaemia. Eur J Haematol 1996;57(Suppl.):23-30.
  • Issaragrisil S, Kaufman DW, Anderson TE, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakham Y, Vannasaeng S, Leaverton PE, Shapiro S, Young NS, and the Aplastic Anemia Study Group. An association of aplastic anemia in Thailand with low socioeconomic status. Br J Haematol 1995;91:80-4.
  • Issaragrisil S, Sriratanasatavorn C, Piankijagum A, Vannasaeng S, Porapakkham Y, Leaverton PE, Kaufman DW, Anderson TE, Shapiro S, Young NS, and the Aplastic Anemia Study Group.  Incidence of aplastic anemia in Bangkok.  Blood 1991;77:2166-8.