Brief Title
Drug Etiology of Aplastic Anemia and Related Dyscrasias
Brief Summary
To determine the role of drugs in the etiology of aplastic anemia, agranulocytosis, and
thrombocytopenic purpura. Drugs used in chemotherapy and immunotherapy were excluded.
Detailed Description
BACKGROUND:
It was well established that drugs played a role in the etiology of aplastic anemia,
agranulocytosis, and thrombocytopenic purpura. In 1985, much of the evidence concerning the
relation of exposure to drugs to the risk of the three dyscrasias was based on case reports.
Such reports could sometimes be appropriate for raising hypotheses, but they rarely served to
establish associations firmly. They could also be subject to selection bias due to a tendency
to publish reports only when a dyscrasia followed the use of a drug already under suspicion,
and could result in spurious and non-causal associations. Moreover, since denominator
populations were not known, case reports could never provide quantitative estimates of
associations, either in terms of their magnitude or of the incidence rates attributable to
the specific exposures The sparse quantitative information that did exist was of variable
quality because of methodological and other difficulties. And while overall incidence rates,
within orders of magnitude, could be estimated for the three dyscrasias, there was virtually
no acceptably reliable information available on the incidence rates due to specific drugs.
Even for well known associations such as aplastic anemia with chloramphenicol, estimates of
incidence, if given at all, were imprecise.
The list of drugs incriminated at one time or another in the etiology of each dyscrasia was
as long as the pharmacopoeia itself. Based on the clinical evidence, however, there were
patterns for each dyscrasia, some of which overlapped. Drugs commonly linked to aplastic
anemia included chloramphenicol, phenylbutazone, oxyphenbutazone, sulfonamides, and
antithyroid drugs; all of them, except chloramphenicol, were also implicated in the etiology
of agranulocytosis, together with phenothiazine derivatives. The same drugs were commonly
linked to thrombocytopenia, which had also frequently been linked to the use of quinidine.
The exact listing of drugs related to each disorder varied between reports and, presumably,
between patterns of drug use in different populations. One major concern in 1985 was with all
of the newer nonsteroidal anti-inflammatory drugs currently on the market in the United
States. There were numerous case reports implicating these drugs in the etiology of all three
dyscrasias.
DESIGN NARRATIVE:
The design was that of a case-control study. All hospitals with at least 100 beds in
geographically defined areas of eastern Massachusetts and Rhode Island were enrolled. All
cases of aplastic anemia and agranulocytosis were identified prospectively for the purpose of
estimating incidence rates. A proportion of cases of thrombocytopenic purpura were identified
but incidence rates were not estimated. The eligibility of cases was determined by a
committee of hematologists, according to strict diagnostic criteria. All identified cases of
the dyscrasias, suitable hospital controls, and, in Massachusetts, neighbor controls were
interviewed. Information was obtained on drug use, occupational and chemical exposure,
personal data, and relevant medical history. The data were used to quantify known
associations between the three dyscrasias and drug use, to identify and quantify previously
unsuspected associations, and to document absence of associations for commonly used drugs.
Incidence rates of aplastic anemia and agranulocytosis attributable to specific drugs and
classes of drugs were estimated.
The study completion date listed in this record was obtained from the "End Date" entered in
the Protocol Registration and Results System (PRS) record.
Study Type
Observational
Condition
Blood Disease
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Start Date
April 1985
Completion Date
June 1992
Gender
Male
Ages
N/A - 100 Years
Accepts Healthy Volunteers
No
Contacts
, ,
Administrative Informations
NCT ID
NCT00005302
Organization ID
3003
Secondary IDs
R01HL031768
Study Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor
, ,
Verification Date
May 2000