salicylates and Anemia--Hemolytic

Topics: Anaphylaxis; Anemia, Hemolytic; Antigen-Antibody Reactions; Desensitization, Immunologic; Drug Eruptions; Drug Hypersensitivity; Epinephrine; Fever; Histamine H1 Antagonists; Humans; Jaundice; Lupus Erythematosus, Systemic; Prednisone; Salicylates; Serum Sickness; Skin Tests; Thrombocytopenia

Topics: Aged; Anemia, Hemolytic; Dermatitis, Exfoliative; Diflunisal; Drug Hypersensitivity; Female; Humans; Liver Function Tests; Middle Aged; Prednisone; Salicylates

Diflunisal [5-(2,4-difluorophenyl)-salicylic acid] is a new analgesic antiinflammatory drug that, when administered orally to rabbits at 40 and 60 mg/kg/day, caused terata, most commonly axial skeletal defects. These same dosage levels also caused a severe maternal hemolytic anemia following a dramatic decrease in erythrocyte ATP levels. The teratogenicity, anemia, and depletion of ATP were unique to the rabbit among species examined. To test the possible causality between the teratogenic effects and anemia induced by diflunisal, a single dose of 180 mg/kg diflunisal was administered to rabbits on gestation day 5. This treatment produced an anemia that persisted through gestation day 15 in addition to causing the characteristic axial skeletal defects. Since diflunisal was cleared from maternal blood before gestation day 9, the critical day for induction of similar axial skeletal defects by hypoxia, the skeletal malformations probably resulted from maternal hypoxia secondary to anemia and not from a direct and specific effect of the drug on the embryo. In addition, we observed that the diflunisal level in the embryo was less than 5% of the peak maternal blood level probably as a result of high plasma protein binding of diflunisal in the maternal blood (greater than 98%). This relatively low placental transfer may explain the lack of diflunisal teratogenicity in rats and mice compared to aspirin which crosses the placenta more readily. These studies demonstrate that a species that exhibits unusually severe drug-specific maternotoxicity is probably an unsuitable model for the prediction of the teratogenic potential of that drug in humans.

Topics: Abnormalities, Drug-Induced; Adenosine Triphosphate; Anemia, Hemolytic; Animals; Antioxidants; Aspirin; Diflunisal; Erythrocytes; Female; Gestational Age; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Hematologic; Rabbits; Rats; Rats, Inbred Strains; Salicylates

Salicylate is known to uncouple mitochondrial oxidative phosphorylation. Since the viability of pyruvate-kinase-deficient reticulocytes depends on ATP generated by mitochondrial metabolism, this study examined the effects of salicylate on erythrocytes deficient in pyruvate kinase. When deficient erythrocytes from patients with severe hemolysis were incubated with salicylate (2 to 30 mg per deciliter), there was a marked decrease (25 to 75 percent) in ATP. In addition, this drug-induced ATP depletion produced cell potassium and water loss, and the normal oxidant responsiveness of the hexose-monophosphate shunt was blunted. Since these cellular abnormalities are associated with accelerated hemolysis in vivo, the data suggest that aspirin therapy may aggravate hemolysis in patients with pyruvate kinase deficiency whose erythrocyte manifest sensitivity to salicylate in vitro.

Topics: Adenosine Triphosphate; Anemia, Hemolytic; Aspirin; Erythrocytes; Glucose; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Hexoses; Humans; Mitochondria; Oxidative Phosphorylation; Pyruvate Kinase; Salicylates

Topics: Adult; Anemia, Hemolytic; Blood Cell Count; Blood Group Antigens; Blood Transfusion; Child; Child, Preschool; Female; Glucosephosphate Dehydrogenase Deficiency; Hemoglobinopathies; Hemoglobinuria; Humans; Male; Prednisolone; Salicylates; Sri Lanka; Thalassemia

Topics: Anemia; Anemia, Hemolytic; Barbiturates; Catalase; Cholinesterases; Genetics, Medical; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Humans; Hydrogen Peroxide; Isoniazid; Malaria; Pharmacogenetics; Pharmacology; Porphyrias; Primaquine; Salicylates; Succinylcholine; Toxicology

Topics: Acetanilides; Aminosalicylic Acid; Aminosalicylic Acids; Anemia; Anemia, Hemolytic; Antibodies; Antigen-Antibody Reactions; Benzoates; Drug Hypersensitivity; p-Aminohippuric Acid; Phenacetin; Salicylates; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Anemia; Anemia, Hemolytic; Antimalarials; Antipyretics; Erythroblastosis, Fetal; Female; Fetal Diseases; Glucosephosphate Dehydrogenase Deficiency; Glucosephosphates; Humans; Hyperbilirubinemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Jaundice; Jaundice, Neonatal; Maternal-Fetal Exchange; North Carolina; Novobiocin; Pregnancy; Salicylates; Sulfisoxazole; Toxicology; Vitamin K

Topics: Anemia; Anemia, Hemolytic; Animals; Antineoplastic Agents; Cortisone; Cricetinae; Fibrosarcoma; Neoplasms; Neoplasms, Experimental; Salicylates; Sodium Salicylate

Topics: Anemia; Anemia, Hemolytic; Humans; Salicylates