Drug-Induced Aplastic Anemia

The most serious side effects associated with acetazolamide are blood dyscrasias.Thrombocytopenia, agranulocytosis, and aplastic anemia have all occurred in patients taking acetazolamide however, drug-induced blood dyscrasias are extremely rare. 

Oral use of sulfonamides, pyrimethamine, and trimethoprim can canse blood dyscrasias such as hemolytic anemia, aplastic anemia, lenkopenia, and agran-nlocytosis. Becanse these blood changes are due to a drug-induced folic acid deficiency, administering folinic (not folic) acid can coimteract the toxicity. Use of folinic acid bypasses the need fc>r dihydrofolate reductase by supplying the fully reduced folate. 

Pisciotta AV. Drug-induced leukopenia and aplastic anemia. CUn Pharmacol Ther 1971 12(1) 13 3. 

Nagao T, Mauer AM. Concordance for drug-induced aplastic anemia in identical twins. N Engl J Med 1969 281(1) 7-11. 

The most common drug-induced hematologic disorders in- elude aplastic anemia, agranulocytosis, megaloblastic anemia, thrombocytopenia, and hemolytic anemia. 

By most reports, idiosyncratic drug-induced hematologic disorders are rare. Relatively few epidemiologic studies have addressed the actual incidence of these adverse reactions. A report from The Netherlands estimated the incidence of drug-associated agranulocytosis as 1.6 to 2.5 cases per million inhabitants per year. Similar results were found in epidemiologic studies conducted in Thailand and BraziU Older data from a study conducted in Europe and Israel estimated the incidences of aplastic anemia and agranulocytosis to be 0.5 and 3.1 cases per million per year, respectively. ... 

The incidence of drug-induced aplastic anemia is estimated at 0.5 to 7.8 cases per 1 million population per year. Higher rates of occurrence have been seen in patients taking antirheumatic drugs such as indomethacin, penicillamine, and gold compounds. Table 102-1 lists drugs that have been associated with drug-induced aplastic anemia. 

The cause of drug-induced aplastic anemia is damage to the... 

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. ... 

Malkin D, Koren G, Saunders EF. Drug-induced aplastic anemia patho-... 

Myelosuppressant chemotherapy, in bone marrow transplantation, to reduce length of drug-induced neutropenia (aplastic anemia, hairy cell leukemia, AIDS)... 

In addition to aplastic anemia, more bone marrow selective drug-induced hypoplasias have been reported. For example, clozapine-induced agranulocytosis occurs in... 

Malkin, D., Koren, G., 8c Saunders, E. F. (1990 Winter). Drug-induced aplastic anemia Pathogenesis and clinical aspects. The American Journal of Pediatric Hematology/Oncology, 12(4), 402—410. 

All medications suspected to be possible triggers for the disease should be discontinued. Supportive measures, especially blood transfusions, are often necessary for treatment of anemia and bleeding complications. Drug-induced aplastic anemia is treated like the idiosyncratic form of the disease, and responds to therapy at about the same rate. Overall, immtmosuppressive therapy produces significant improvement in more than half of all patients younger individuals have a considerably better prognosis than those who are older than 45 years (Young et al. 2008). 

The role of immunity in anemic or thrombocytopenic reactions produced by these drugs has been less well studied, in part because of their lower frequency. Oxyphenbutazone was recently reported to be the commonest cause of drug-induced aplastic anemia in Sweden (Bottiger and Westerholm 1973). A positive lymphocyte transformation test has been reported in a patient with phenylbutazone-induced aplastic anemia (Reidenberg and Caccese 1975), suggesting an immune response to the drug and conceivably immune suppression of erythropoiesis, but further studies are needed. 

Thomas D, Moisidis A, Tsiakalos A, Alexandraki K, Syriou V, Kaltsas G. Antithyroid drug-induced aplastic anemia. Thyroid 2008 18(10) 1043-8. 

The perchlorate ion of potassium perchlorate, KCIO4, is a competitive inhibitor of thyroidal 1 transport via the Sodium Iodide Symporter (NIS).This drug can cause fatal aplastic anemia and gastric ulcers and is now rarely used. If administered with careful supervision, in limited low doses and for only brief periods, serious toxic effects can be avoided. The compound is especially effective in treating iodine-induced hyperthyroidism, which may occur, for example, in patients treated with the antiar-rhythmic compound amiodarone. Perchlorate ion can also be used in a diagnostic test of 1 incorporation into Tg, the so-called perchlorate discharge test. 

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