Download drugs induced hematologic disorders

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.