Hemolytic anemia penicillin-induced

Type II, or cytolytic, reactions are mediated by both IgG and IgM antibodies and usually are attributed to their ability to activate the complement systerrr The major target tissues for cytolytic reactions are the cells in the circulatory system. Examples of type II allergic responses include penicillin-inhemolytic anemia, methyldopa-indMced autoimmune hemolytic anemia, quinidine-induced thrombocytopenic purpura, and sulfonamide-induced granulocytopenia. These autoimmune reactions to drugs usually subside within several months after removal of the offending agent. 

The answer is a. (Katzung, p 162.) Many drugs can cause an immunohemolytic anemia. Methyldopa may cause a positive Coombs test in as many as 20% of patients, along with hemolytic anemia. Other drugs with similar actions on red blood cells are penicillins, quinidine, procainamide, and sulfonamides. These form a stable or unstable hapten on the red cell surface, which induces an immune reaction I immunoglobulin G (IgG) antibodies] and leads to dissolution of the membrane. 

In contrast to a-methyldopa-induced hemolytic anemia, most drug-induced hemolytic anemia, especially for penicillins [34] and cephalosporins [35], involves drug-dependent antibodies, presumably because the drug acts as a hapten to directly modify erythrocytes or form immune complexes [36], However, there are many examples where a drug, such as nomifensine, induces both drug- (or metabolite)-dependent and drug-... 

Antibiotics Isoniazid Penicillins Hypersensitivity and Autoimmunity Rash, dermatitis, vasculitis, arthritis, drug-induced SLE Anaphylaxis, dermatitis vasculitis, serum sickness, hemolytic anemia... 

Autoantibodies to red blood cells and autoimmune hemolytic anemia have been observed in patients treated with numerous drugs, including procainamide, chlor-propaminde, captopril, cefalexin, penicillin, and methyldopa (Logue et al., 1970 Kleinman et al., 1984). Hydralazine- and procainamide-induced autoantibodies may also result in SLE. Approximately 20% of patients administered methyldopa for several weeks for the treatment of essential hypertension developed a dose-related titer and incidence of autoantibodies to erythrocytes, 1% of which presented with hemolytic anemia. Methlydopa does not appear to act as a hapten but appears to act by modifying erythrocyte surface antigens. IgG autoantibodies then develop against the modified erythrocytes. 

The IgD profile in a normal Nigerian population was similar to that of the British and American populations (T7). Interestingly, in more than half the patients with African trypanosomes, IgD was absent from their sera (M35). Three out of six diabetic patients had insulin antibodies of the IgD class (D3), and IgD levels were five to six times higher in Ethiopian children than in Swedish children of the same age (J4). Patients with penicillin-induced hemolytic anemia had IgD receptors on their erythrocyte surfaces and sera from some subjects allergic to penicillin G were shown to have IgD antibodies specific for the benzyl-penicilloyl-antigenic determinant of this antibiotic (C19). 

Kerr RO, Cardamone J, Dalmasso AP, Kaplan ME. Two mechanisms of erythrocyte destruction in penicillin-induced hemolytic anemia. N Engl J Med 1972 287(26) 1322-5. 

An immunologically induced hemolytic anemia due to penicillin or its congeners occurs but is rare (44—47). It typically occurs during treatment with high doses (over 10 million units/day) of penicillin for more than 2 weeks (44,45,48). The dose- and time-dependence of this reaction appear to be explained by the underlying mechanism. 

Besides this hapten or penicillin-type of drug-induced hemolysis, a second less frequent mechanism, the so-called innocent bystander mechanism can occur (46,49,50). Penicillin-antibody complexes are only loosely bound to erythrocytes and activate complement, which can be detected on the erythrocyte surface with the complement antiglobulin test ( complement or nongamma type). This mechanism plays a part in immune hemolytic anemias due to various drugs other than penicillins. The hemolytic reaction can continue for weeks after withdrawal of penicillin, that is as long as sufficient penicillin-coated erythrocytes and specific antibodies remain in circulation. 

A classic example is penicillin-induced hemolytic anemia. Associated with long-term use of the drug, it is caused by hapten-red blood cell complexes... 

In one clinical situation, the nature of the autologous carrier may be rather clearly defined this is in drug-induced hemolytic anemia based on immunologic mechanisms. It has been shown that destruction of erythrocytes is due to interaction of IgG antibodies with the red cell membrane after its appreciable penicilloy-lation during therapy with high doeses of penicillin (Levine and Redmond 1967). The antibodies involved were penicilloyl specific but it appeared possible that modified structures of the red cell surface are also contributing to the specificity. If this can be substantiated, the erythrocyte will be definitively implicated as the actual immunogenic carrier. 

Levine BB (1971) Genetic factors in reagin production in mice. In Austen KF, Becker EL (eds) Biochemistry of the acute allergic reactions. Blackwell, Oxford Levine BB, Redmond AP (1967) Immunochemical mechanisms of penicillin-induced Coombs positivity and hemolytic anemia in man. Int Arch Allergy Appl Immunol 31 594-606... 

Van Arsdel PP Jr (1978) Adverse drug reactions. In Middleton E Jr, Reed CE, Ellis EF (eds) Allergy principles and practice, vol 2. Mosby, St. Louis, p 1133 Van Arsdel PP Jr, Franz KB (1963) Nature of antibody in penicillin-induced hemolytic anemia. J Clin Invest 42 988... 

Amos HE, Bishop ANR, Seaman MJ, Trowell J (1968) Penicillin induced hemolytic anemia. Br Med J 3 439... 

The evaluation of anti-BPO antibodies of the IgG class, by a similar procedure to the one used in the RAST assay, has proved of interest in the evaluation of penicillin-induced hematological disorders, such as hemolytic anemia or leukopenia (Neftel et al. 1981), although anti-BPO IgG antibodies are also encountered in asymptomatic individuals treated with high doses of penicillins. Previously described methods, such as hemagglutination or bacteriophage inhibition, are cumbersome, less reproducible, and may be considered as obsolete. 

Immunologically induced hemolytic anemia can occur by at least three independent mechanisms typified by the drugs stibophen, penicillin, and methyldopa. 

Dawson RB, Segal BL (1966) Penicillin-induced hemolytic anemia. Arch Intern Med 118 575... 

Kerr RO, Cardamone J, Dalmasso AP, Kaplan ME (1972) Two mechanisms of erythrocyte destruction in penicillin-induced hemolytic anemia. N Engl J Med 287 1322 Klein KG, Parkin JD, Madaras F (1976) Studies on an acquired inhibition of factor VIII induced by penicillin allergy. Clin Exp Immunol 26 155 Klemola E (1970) Hypersensitivity reactions to ampicillin in cytomegalovirus mononucleosis. Scand J Infect Dis 2 29... 

Ries CA, Rosenbaum TJ, Garratty G (1975) Penicillin-induced hemolytic anemia. JAMA 233 432... 

Unlike the other types of hypersensitivity caused by antibodies, namely types II and ni, only a proportion of the population, the so-called atopies, have a predisposition to developing a type 1 hypersensitivity reaction when exposed to the allergen in question. Atopy may have a genetic component but type 11 and III reactions like, for example, penicillin-induced hemolytic anemia and serum sickness, may occur in all individuals, and this may result without a prior sensitization phase. 

Hematologic Cases of penicillin-induced hemolytic anemia continue to be reported [107 ]. The risk appears to be especially high in patients with cystic fibrosis, which might be explained by the frequent use of penicillins, including piperacillin, combined with a hyperimmune state. More cases have been reported [108, 109 ]. 

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