DRUGS INDUCED HEMATOLOGIC DISORDERS

Drugs may produce hematologic toxicity by one of three general mechanisms: 1) direct drug (or a metabolite) toxicity 2) toxicity due to a drug effect on a genetic abnormality in the bone marrow 3) toxicity involving immune mechanisms. The four major blood dyscrasias attributable to drugs are: 1) agranulocytosis or leukopenia (loss of the white blood cells) 2) aplastic anemia (loss of all the formed elements of the blood) 3) thrombocytopenia (loss of the platelets) 4) hemolytic anemia (loss of the red blood cells). The incidence of these adverse hematologic drug reactions, the relative importance of various etiologic chemicals, and their resultant morbidity and mortality vary.

1. Drugs Suspected of Inducing Agranulocytosis (Leukopenia) Drug-induced agranulocytosis is classified as Type 1 (due to an immune mechanism) and Type II (drug effect on bone marrow DNA synthesis). In Type I reactions, blood immunoglobins are directed against drug-related antigens located on circulating leukocytes. Allopurinol* Aminopyrine Chloramphenicol Chlordiazepoxide Chloroquine Chlorpromazine Indomethacin Mefenamic acid Penicillamine Anticonvulsants Antimalarials Aspirin Captopril Cephalosporins Chlorthalidone Cimetidine Clindamycin Diazepam Isotretinoin L-dopa Mercurial diuretics Methyldopa Naproxyn Nitrofurantoin Penicillins Phenothiazines Piroxicam

Phenylbutazone Phenytoin Quinidine Rifampicin Sulfonamides Thiazides Acetaminophen Acetazolamide

Diflunisal Doxycycline Fenoprofen Gentamicin Griseofulvin Hydralazine Ibuprofen Isoniazid

Procainamide Propranolol Spironolactone Streptomycin Sulfonylureas Sulindac Tolmetin Vancomycin

* Underlined drugs are most significant. Many of these other drugs have been implicated in only one or a few case reports.

2. Drugs Suspected of Inducing Aplastic Anemia Aplastic anemia is an unexpected peripheral-blood pancytopenia with variable bone marrow hypocellularity in the absence of underlying malignant or myeloproliferative disease. Severe aplastic anemia is seen with a bone marrow of less than 25% of normal cellularity or a bone marrow of less than 50% of normal cellularity with less than 30% of the hematopoietic cells and at least two of the following peripheral blood values: 1) granulocytes fewer than 500/mm3 2) platelets fewer than 20,000/mm3 3) anemia with reticulocytes fewer than 1%. 15 About 65% of people with aplastic anemia die within 4 months of diagnosis; few die after this 4-month period.' Allopurinol* Aminopyrine Chloramphenicol Chloroquine Gold salts Indomethacin Mefenamic acid Phenylbutazone Propylthiouracil Sulfonamides Acetaminophen Aspirin Benzene Captopril Chlordiazepoxide Chlorpromazine Fenoprofen Indoprofen Naproxyn Organic solvents Phenytoin Piroxicam Sulfonylureas Sulindac Thiazides Thiocyanate

*Underlined drugs are most significant. Many of these other drugs have been implicated in only one or a few case reports.

3. Drugs Suspected of Inducing Thrombocytopenia Drug-induced immune thrombocytopenia is characterized by acute purpura, confluent petechiae or ecchy-moses- particularly after mild trauma-and gastrointestinal, central nervous system, or urinary tract bleeding,all associated with a mild or severe lack of blood platelets. Drugs may induce marrow hypoplasia, destroy platelets directly, or be responsible for an immune reaction. Thrombocytopenia may be associated with several disease states (acute leukemia, Gaucher's disease, systemic lupus erythematosus, sarcoidosis); drug-induced thrombocytopenia usually remits 1 to 2 weeks after drug discontinuance. Gold salts* Indomethacin Mefenamic acid Quinidine Quinine Thiazides Acetaminophen Aminopyrine Amiodarone Aspirin Codeine Danazol Diclofenac Digitoxin Fenoprofen Heparin Ibuprofen Isotretinoin Para-aminosalicyclic acid Phenytoin Piroxicam Ranitidine Sulindac Tolmetin

*Underlined drugs are most significant. Many of these other drugs have been implicated in only one or a few case reports.

4. Drugs Suspected of Inducing Hemolytic Anemia Aminopyrine* Methyldopa Quinidine Acetaminophen Aspirin Cephalosporins Chlorpromazine Phenytoin Diclofenac Ibuprofen L-dopa Mefenamic acid Naproxyn Penicillins Phenylbutazone Quinine Rifampicin Sulfonamides Sulindac Tetracyclines Thiopental Volatile nitrites

*Underlined drugs are most significant. Many of these other drugs have been implicated in only one or a few case reports.