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American Journal of Hematology Apr 2003The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and...
The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated. This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression. From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified. The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively. The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates. Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics. The increase in risk of neutropenia predominantly occurred during the first months of treatment. For most drugs investigated in this study, there was no relationship to daily dose. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state. In conclusion, the highest risks of neutropenia were generally found in patients starting treatment. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state.
Topics: Adolescent; Adult; Aged; Agranulocytosis; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Databases, Factual; England; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Neoplasms; Neutropenia; Odds Ratio; Pharmaceutical Preparations; Risk Factors; Wales
PubMed: 12666135
DOI: 10.1002/ajh.10295 -
Drugs in R&D Mar 2017Agranulocytosis is a rare but serious complication of antithyroid drug therapy, and an up-to-date understanding of this topic is important. Both direct toxicity and... (Review)
Review
Agranulocytosis is a rare but serious complication of antithyroid drug therapy, and an up-to-date understanding of this topic is important. Both direct toxicity and immune-mediated responses have been described as possible mechanisms. Some major susceptibility loci have recently been identified, which may lead the diagnosis of agranulocytosis into a genomic era. Onset is acute and patients present with symptoms and signs of infection together with high fever. Clinical suspicion is pivotal and should prompt blood sampling. An absolute neutrophil count of <500/μl in the presence of antithyroid drugs establishes the diagnosis. The causative drug should immediately be stopped to prevent further damage. Treatment includes broad-spectrum antibiotics and granulocyte-colony stimulation factor in selected patients. Later, patients will need definitive treatment for hyperthyroidism, usually with radioactive iodine or surgery. The best way to avoid the mortality associated with antithyroid drug-induced agranulocytosis is patient education.
Topics: Agranulocytosis; Antithyroid Agents; Humans; Risk Factors
PubMed: 28105610
DOI: 10.1007/s40268-017-0172-1 -
British Medical Journal Jul 1955
Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Humans
PubMed: 14389741
DOI: 10.1136/bmj.2.4933.246 -
Clinical & Developmental Immunology 2013The clinical course of chronic lymphocytic leukemia (CLL) may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as... (Review)
Review
The clinical course of chronic lymphocytic leukemia (CLL) may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Pure red cell aplasia (PRCA) and autoimmune agranulocytosis (AG) are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.
Topics: Agranulocytosis; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Autoimmunity; Humans; Immunologic Factors; Leukemia, Lymphocytic, Chronic, B-Cell; Red-Cell Aplasia, Pure; Rituximab; Thrombocytopenia
PubMed: 23690826
DOI: 10.1155/2013/730131 -
British Medical Journal Mar 1953
Topics: Adrenocorticotropic Hormone; Agranulocytosis; Cortisone
PubMed: 13019118
DOI: No ID Found -
British Medical Journal Jan 1980
Topics: Agranulocytosis; Clozapine; Dibenzazepines; Dyskinesia, Drug-Induced; Humans; Leukemia
PubMed: 7427106
DOI: 10.1136/bmj.280.6209.255-b -
BMJ (Clinical Research Ed.) Jul 1994
Topics: Agranulocytosis; Clozapine; Humans
PubMed: 8044077
DOI: 10.1136/bmj.309.6946.54b -
The Western Journal of Medicine May 1977Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of...
Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of the neutrophilic granulocyte count. Granulocytopenia occurs in about 4 percent and agranulocytosis occurs in about 0.3 percent of treated patients. Although this depression of the granulocyte count is reversible after the drug is discontinued, serious infection frequently accompanies agranulocytosis and accounts for almost all deaths related to the drugs. It is important to be aware of the clinical features of granulocytopenic reactions due to antithyroid drugs.
Topics: Agranulocytosis; Humans; Hypothyroidism; Methimazole; Propylthiouracil
PubMed: 867981
DOI: No ID Found -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9 -
The American Journal of Case Reports Sep 2018BACKGROUND Vancomycin has been used for decades to treat infections by Gram-positive bacteria, particularly those caused by methicillin-resistant staphylococci.... (Review)
Review
BACKGROUND Vancomycin has been used for decades to treat infections by Gram-positive bacteria, particularly those caused by methicillin-resistant staphylococci. Agranulocytosis is an infrequent complication of this antibiotic, postulated in its genesis a mechanism immune-mediated by antineutrophil antibodies and antineutrophil cytoplasm antibodies (ANCA). Treatment includes discontinuing vancomycin, and granulocyte colony-stimulating factor administration. CASE REPORT We present the case of a patient who developed agranulocytosis secondary to vancomycin during the treatment of an infectious endocarditis, which was reversed when the antibiotic was stopped. Concomitantly to neutropenia, he had ANCA positivity, which subsequently became negative. CONCLUSIONS Agranulocytosis induced by vancomycin is infrequent and generally occurs after day 12 of treatment. In most cases, like in our case, it is caused by an immune-mediated mechanism. More studies are needed to determine the pathogenic mechanism and the ANCA role in this adverse effect.
Topics: Abdominal Abscess; Adult; Agranulocytosis; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Endocarditis, Bacterial; Granulocyte Colony-Stimulating Factor; Humans; Kidney Diseases; Male; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Urinary Tract Infections; Vancomycin
PubMed: 30174327
DOI: 10.12659/AJCR.909956