(c) The most common characteristics of this group of drugs in causing
immune abnormalities are:
1 The patient needs to take only a small quantity of drug.
2 Acute intravascular hemolysis with hemoglobinemia and
hemoglobinuria is the usual clinical presentation.
3 The antibody is often lgM.
4 Patient's RBCs are often sensitized with complement alone.
5 "In vitro" reactions (agglutination, hemolysis, and/or
sensitization to antiglobulln serum) are only obvious when patient's serum, drug, and
RBCs are incubated together.
Drug absorbed onto RBCs.
(a) Unlike the previous group of drugs, the penicillins and
cephalosporins (and possibly carbromal and methadone) bind firmly to the RBC
membrane. Considerable experimental work has demonstrated that the
immunogenicity is a result of its ability to react chemically with tissue proteins to form
several different haptenic groups. The major haptenic determinant is the
benzylpenicilloyl (BPO) group. Approximately three percent of patients receiving
massive doses of intravenous penicillin will develop a positive direct antiglobulin test,
and some of these will develop hemolytic anemia. The mechanism of the positive direct
antiglobulin test and hemolytic anemia seems clear. The drug is absorbed to the RBCs.
A immune antibody, for example, antipenicillin, is produced by the patient and will react
with the penicillin on the RBCs. The end-product, therefore, is a RBC sensitized with
lgG. Complement is not usually involved in this reaction, and, thus intravascular
hemolysis does not usually occur. The red blood celIs are destroyed extravascularly by
the reticuloendothelial system, probably in the same way as red cells sensitized with
lgG blood group alloantibodies (for example, Rh). If a sensitive enough technique is
used, most serums can be shown to contain penicillin (BPO) antibodies. Most serums
contain low-titer lgM antibodies alone; some contain IgG in addition. The high
percentage of penicillin antibodies in the normal population is probably because of the
continual exposure to penicillin in our modern environment. It should be noted that
there is no direct correlation between the presence of penicillin hemagglutinating
antibodies, and allergic reactions.
(b) The clinical and laboratory features of penicillin-induced immune
hemolytic anemia are as follows:
1 Hemolysis typically develops only in patients receiving very
large doses of penicillin (at least 10 million units daily for a week or more).