Penicillin hemolytic anemia with

T cells control these learned responses and decide which tools to use in the reaction. Sometimes they choose several different tools at once, and multiple reactions ensue, such as when a person becomes sensitized to penicillin and has not only anaphylaxis but hemolytic anemia and serum sickness. There are different types of T cells, and they communicate either directly with other cells or by chemical messages called cytokines. The pattern of cytokines released is one way T cells have of determining which kind of response will occur. They are broadly called Thl andTh2 responses, with Thl mostly responding to infections and Th2 often producing allergy or asthma. 

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. 

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). 

Hematologic/Lymphatic Anemia hemolytic anemia thrombocytopenia thrombocytopenic purpura eosinophilia leukopenia granulocytopenia neutropenia bone marrow depression agranulocytosis reduction of hemoglobin or hematocrit prolongation of bleeding and prothrombin time decrease in WBC and lymphocyte counts increase in lymphocytes, monocytes, basophils, and platelets. Hypersensitivity Adverse reactions (estimated incidence, 1% to 10%) are more likely to occur in individuals with previously demonstrated hypersensitivity. In penicillin-sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immediate and severe. 

Cephalosporins are sensitizing and may elicit a variety of hypersensitivity reactions that are identical to those of penicillins, including anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, and hemolytic anemia. However, the chemical nucleus of cephalosporins is sufficiently different from that of penicillins so that some individuals with a history of penicillin allergy may tolerate cephalosporins. The frequency of cross-allergenicity between the two groups of drugs is uncertain but is probably around 5-10%. However, patients with a history of anaphylaxis to penicillins should not receive cephalosporins. 

The newer derivatives seem less likely to cause hypersensitivity reactions, perhaps because the protein adducts generated are shorter lived. All four types of hypersensitivity reaction have been observed with penicillin. Thus, high doses may cause hemolytic anemia and immune complex disease and cell-mediated immunity may give rise to skin rashes and eruptions, and the most common reactions are urticaria, skin eruptions, and arthralgia. Antipenicillin IgE antibodies have been detected consistently with an anaphylactic reaction. The anaphylactic reactions (type 1 see above), which occur in 0.004% to 0.015% of patients, may be life threatening. 

Blood dyscrasias, mostly dose independent, are among the most important allergic-type adverse reactions to drugs. Aplastic anemia is a serious but rare (presumably) idiosyncratic reaction. It has been reported in association with chloramphenicol, quinacrine, phenylbutazone, mephenytoin, gold compounds, and potassium chlorate. Hemolytic anemia, thrombocytopenia, and agranulocytosis may result from an unusual, acquired sensitivity to a variety of widely used drugs including aminopyrine, phenylbutazone, phenothiazines, propylthiouracil, diphenylhydantoin, penicillins, chloramphenicol, sulfisoxazole, and tolbutamide. 

The major adverse reactions to the penicillins are hypersensitivity responses. Manifestations of hypersensitivity inclnde nrticaria, angioedema, and anaphylaxis (type 1 reaction) hemolytic anemia (type 11 reaction) interstitial nephritis, vascnlitis, and serum sickness (type 111 reaction) and contact dermatitis or Stevens-Johnson syndrome (type IV reaction). A maculopapular rash occnrs late in the treatment course of 2% to 3% of patients receiving a penicillin drug. Once a patient has had a hypersensitivity response to a penicillin, it is probable, bnt not certain, that a reaction will occur with exposure to the same penicillin or to any other penicillin. Intradermal skin tests can predict whether a patient is at risk for developing a hypersensitivity reaction to the penicillins. If the resnlts are positive, penicillins should generally be avoided. 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

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... 

Vasculitis may be related to penicillin hypersensitivity. The Coombs reaction frequently becomes positive during prolonged therapy, but hemolytic anemia is rare. Reversible neutropenia has been noted, occurring in up to 30% of patients treated with 8-12 g nafcillin for longer than 21 days. Eosinophilia occasionally accompanies other allergic reactions to penicillin. 

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. 

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. 

Penicillins can cause all four types of hypersensitivity responses provoking type I IgE-mediated reactions such as urticaria, angioedema, asthma, and anaphylaxis type n antibody-mediated hemolytic anemia and thrombocytopenia type III immune complex-mediated serum sickness-like reactions and vasculitis and type IV T cell-mediated contact dermatitis, rashes, and other skin eruptions (refer to Chaps. 2 and 3). Table 5.1 lists clinical adverse reactions, together with their immune... 

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