Aplastic anemia chloramphenicol-induced

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

Exceptions, however, to this situation may occur for some drugs, particularly those possessing inherent properties that can threaten human health. One such example is chloramphenicol, which has been implicated as the causative agent in many cases of fatal aplastic anemia, a condition reported to be non-dose-related and potentially could be induced by even extremely low levels of this antibiotic in food (30). Thus, the establishment of a safe level in chloramphenicol residue exposure from food animal tissues can be precluded. 

Adverse events are sometimes termed type A (usually pharmacologically predictable, relatively frequent, seldom fatal and usually identified during clinical trials) or type B (unpredictable idiosyncratic reactions which are usually infrequent but can be very serious or fatal) (Rawlins and Thompson, 1977 Venning, 1983). Postmarketing ADR monitoring usually identifies the more serious, type B reactions. The sample size needed in clinical trials to detect differences between an incidence rate of 1/10 000 and 2/10 000 is about 306 000 patients (e.g. for a placebo comparison of chloramphenicol-induced aplastic anemia, which occurs in 1/30 000 Lasagna, 1983). Clinical trials at this scale are simply impractical. 

Genetic predisposition may also influence the development of drug-induced aplastic anemia. Studies in animals and a case report of chloramphenicol-induced aplastic anemia in identical twins suggest a genetic predisposition to the development of drug-induced aplastic anemia. " Furthermore, pharmacogenetic research that focuses on patients who may be slow or normal metabolizers of drugs may increase the clinician s ability to predict the development of aplastic anemia. Initial case-control studies have not had the power necessary to identify a statistical difference between controls and cases, bnt continued research may establish the role of altered metabolism in this population. ... 

Chloramphenicol causes two distinct forms of toxicity in humans. The most serious form is an irreversible aplastic anaemia. This rare idiosyncratic response (the incidence is 25,000-60,000) may have an immunological component however, the meehanism of chloramphenicol-induced aplastic anemia remains unknown. Neither a dose-response relationship nor a threshold dose for the induction of aplastic anaemia has been established. Aplastic anemia is associated with reduced numbers of erythrocytes, leukocytes, and platelets (pancytopaenia), with resultant bleeding disorders and secondary infections. The condition tends to be irreversible and fatal. By comparison, leukemia may be a sequel of hypoplastic anemia. Because thiamphenicol and florfenicol lack the p-nitro moiety, they do not induce irreversible aplastic anemia in humans. 

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