that appear to react with intrinsic RBC antigens; the serologic test results are
indistinguishable from those seen in the warm autoimmune hemoIytic anemias. Often,
the antibody can be shown to have specificity associated with the Rh system; the serum
antibody behaves independently of the presence or absence of the drug "in vitro".
(b) The clinical and laboratory characteristics of methyldopa-induced
abnormalities are as follows:
1 Positive direct antiglobulin tests are found in 15 of patients
2 The development of a positive direct antiglobulin test is
dose-dependent (for example, approximately 36 percent of patients on 3 gm of drug
daily develop positive direct antiglobulin tests, as compared with only 11 percent on less
than 1 gm daily).
3 The direct antiglobulin test usually becomes positive after three
to six months of treatment.
4 Only 0.5 to 1 percent of patients on methyldopa (Aldomet)
deveIop hemolytic anemia.
5 The RBCs are usually sensitized with only lgG.
6 The antibodies in the serum, and eluate, are indistinguishable in
the laboratory from those found in idiopathic warm autoimmune hemolytic anemia.
7 The positive direct antiglobulin test gradually becomes negative
once methyldopa is stopped. This may take from one month to two years. Hematologic
values usually improve within the first week or so.
(c) One other drug unrelated to methyldopa, mefenamic acid (Ponstel),
has been described as a cause of immune hemolytic anemia with serologic results
identical to methyldopa.
2-10. LABORATORY INVESTIGATION OP DRUG-RELATED PROBLEMS
a. The most commonly encountered problem associated with drugs is the
occurrence of a positive direct antiglobulin test. A positive direct antigloblin test may of
course occur with any of the drugs mentioned in this review, but methyldopa is by far
the most common cause, followed by penicillin. Positive results in indirect antiglobulin
tests obtained without adding drugs to the incubation mixtures are seen only in the
methyldopa group as these are the only drugs that produce antibodies that react with
normal untreated RBCs. The serologic evaluation of positive results of a direct or
indirect antiglobulin test are basically the same as that mentioned earlier in this lesson
in the investigation of autoimmune hemolytic anemia.