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Atencion Primaria Oct 2021
Topics: Agranulocytosis; Clozapine; Humans
PubMed: 34116408
DOI: 10.1016/j.aprim.2021.102114 -
Singapore Medical Journal Feb 2008Clozapine is an atypical antipsychotic with superior efficacy in the treatment of refractory schizophrenia. But it can cause agranulocytosis, which occurs in one to two... (Review)
Review
Clozapine is an atypical antipsychotic with superior efficacy in the treatment of refractory schizophrenia. But it can cause agranulocytosis, which occurs in one to two percent of patients. This paper was prepared to discuss the condoned and controversial issues of therapy with this drug, but only within a haematological context. The feasibility of attempting therapeutically controversial blood monitoring regimes, as opposed to following standardised Western guidelines, given the differences in terms of accessibility, convenience and financial considerations between the public and private sector medical care will also be discussed. The proposal of adopting a structured pro forma, with a risk-benefit assessment, in the event of unavoidable veering from the guidelines may allay medicolegal implications, especially in countries where blood monitoring is not mandatory. It is hoped that this article will stimulate further research in our region, bearing in mind the increasing awareness and focus on genetic polymorphism, and the possibility of drawing up our own monitoring guidelines in the near future.
Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Developing Countries; Drug Monitoring; Humans; Liability, Legal; Patient Education as Topic; Practice Guidelines as Topic; Schizophrenia
PubMed: 18301833
DOI: No ID Found -
British Journal of Haematology Jul 2010Drug-induced agranulocytosis (neutrophil count <0.5 x 10(9)/l) is a rare haematological complication with an incidence of no more than 10 cases per million inhabitants... (Review)
Review
The role of haematopoietic growth factors granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the management of drug-induced agranulocytosis.
Drug-induced agranulocytosis (neutrophil count <0.5 x 10(9)/l) is a rare haematological complication with an incidence of no more than 10 cases per million inhabitants per year in Europe. Over the past few years there has been a steady decline in mortality rate, (currently at <5%), which can be partly explained by earlier recognition and the improved clinical management of associated intercurrent infections that may lead to severe sepsis if left untreated. The true impact of the use of haematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the decreased mortality rate remains unknown. Yet, most studies show that these molecules, especially G-CSF, reduce the duration of agranulocytosis, antibiotic course and length of hospital stay. Their use is particularly recommended in patients with poor prognostic factors, such as a neutrophil count <0.1 x 10(9)/l, age over 65 years, severe infection or multiple co-morbidities. In all cases, the drug responsible for causing the agranulocytosis must be discontinued and remain permanently contraindicated. The appropriate Medicines Regulatory Agency must also be notified of the adverse event.
Topics: Aged; Agranulocytosis; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Prognosis
PubMed: 20151980
DOI: 10.1111/j.1365-2141.2010.08104.x -
Scientific Reports Sep 2017Antithyroid drug (ATD)-induced agranulocytosis is associated with human leukocyte antigen (HLA) and nearby genes in Southeast Asian and European populations. The...
Antithyroid drug (ATD)-induced agranulocytosis is associated with human leukocyte antigen (HLA) and nearby genes in Southeast Asian and European populations. The susceptibility of the Han population from northern China to ATD-induced agranulocytosis has not been reported. We evaluated the associations of genetic variants at the HLA-B and HLA-DRB1 loci and 32 candidate single nucleotide polymorphisms (SNPs) with agranulocytosis in 29 patients with ATD-induced agranulocytosis and in 140 patients with Graves' disease (GD) as controls. All subjects were of Han descent from northern China. HLA-B*27:05 (P = 1.10 × 10), HLA-B*38:02 (P = 2.41 × 10) and HLA-DRB1*08:03 (P = 1.57 × 10) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying the HLA-B*27:05 allele had agranulocytosis. The odds ratios (ORs) comparing allele carriers to non-carriers were 66.24 (95% confidence interval (CI): 3.54-1239.66) for HLA-B*27:05, 7.525 (95% CI: 2.294-24.68) for HLA-B*38:02 and 4.316 (95% CI: 1.56-11.93) for HLA-DRB1*08:03. Two SNPs, rs2596487 (OR = 4.196, 95% CI = 2.086-8.441, P = 2.08 × 10) and rs2228391 (OR = 3.621, 95% CI = 1.596-8.217, P = 1.2 × 10), were independently associated with ATD-induced agranulocytosis. Subjects carrying the 'A' allele of rs1811197 or HLA-B*38:02 showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10 and P = 7.39 × 10, respectively). Our findings support the association between genetic variations of HLA-B and HLA-DRB1 with ATD-induced agranulocytosis in a Han population from northern China.
Topics: Adult; Agranulocytosis; Antithyroid Agents; China; Ethnicity; Female; Genetic Predisposition to Disease; HLA-B27 Antigen; HLA-DRB1 Chains; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Young Adult
PubMed: 28931918
DOI: 10.1038/s41598-017-12350-2 -
BMC Psychiatry Dec 2016Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory... (Comparative Study)
Comparative Study
BACKGROUND
Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia.
METHODS
The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well.
RESULTS
The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine.
CONCLUSIONS
Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.
Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Disease Progression; Electronic Health Records; Female; Hospitals, University; Humans; Iceland; Longitudinal Studies; Male; Middle Aged; Neutropenia; Risk Factors; Schizophrenia; Young Adult
PubMed: 27955666
DOI: 10.1186/s12888-016-1167-0 -
American Journal of Hematology Jan 2006Agranulocytosis and aplastic anemia are both rare, life-threatening blood dyscrasias. Agranulocytosis is mainly caused by medicines, whereas the etiology of aplastic...
Agranulocytosis and aplastic anemia are both rare, life-threatening blood dyscrasias. Agranulocytosis is mainly caused by medicines, whereas the etiology of aplastic anemia is largely unexplained. In two epidemiologic studies using the same methods, we observed a striking inverse relationship between the incidence of the two diseases in different regions, including five countries in Europe, and Israel and Thailand. The annual incidence of agranulocytosis ranged from 1.1 to 4.9 cases per million, and that of aplastic anemia, from 0.7 to 4.1 per million; the inverse correlation was consistent among the regions (R2 = 0.74). There is no clear explanation for this previously unreported pattern, but it seems unlikely to be due to methodology.
Topics: Agranulocytosis; Anemia, Aplastic; Female; Humans; Incidence; Male
PubMed: 16369972
DOI: 10.1002/ajh.20489 -
British Journal of Clinical Pharmacology Sep 2019Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in... (Meta-Analysis)
Meta-Analysis
AIMS
Antithyroid drug (ATD)-induced agranulocytosis is a life-threatening adverse drug reaction. Previous studies suggested that HLA genotypes may play an important role in ATD-induced agranulocytosis. To examine the associations between HLA genotypes and ATD-induced agranulocytosis, we conducted a systematic review and meta-analysis of pharmacogenomics studies.
METHODS
We searched the MEDLINE, Embase and CENTRAL databases on 16 June 2018 for case-control studies on the associations between HLA genotypes with ATD-induced agranulocytosis. The Newcastle-Ottawa scale was used to evaluate the risk of bias of included studies. We conducted random-effects model meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs) to determine the associations between HLA genotypes and ATD-induced agranulocytosis.
RESULTS
We included 5 studies with 142 ATD-induced agranulocytosis cases, 1529 matched ATD-tolerant controls and 5945 healthy controls. The risk of bias of included studies was generally low. ATD-induced agranulocytosis was associated with HLA-B*27:05 (OR 10.97; 95% CI 0.75-159.99), HLA-B*38:02 (OR 19.85; 95% CI 7.94-49.57) and HLA-DRB1*08:03 (OR 5.29; 95% CI 3.44-8.14). After excluding propylthiouracil, the associations of ATD-induced agranulocytosis with HLA-B*27:05 and HLA-B*38:02 were strengthened (OR being 20.61 (95% CI 5.21-81.58) and 40.59 (95% CI 13.24-124.47), respectively). The associations of ATD-induced agranulocytosis with HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 remained significant when compared to population controls (OR being 7.37 (95% CI 3.86-14.07), 36.43 (95% CI 12.80-103.70) and 5.42 (95% CI 2.36-12.47), respectively). HLA-B*27:05, HLA-B*38:02, and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
CONCLUSIONS
HLA-B*27:05, HLA-B*38:02 and HLA-DRB1*08:03 alleles were associated with ATD-induced agranulocytosis, especially in carbimazole/methimazole-induced agranulocytosis.
Topics: Agranulocytosis; Alleles; Antithyroid Agents; Graves Disease; HLA Antigens; Humans
PubMed: 31108563
DOI: 10.1111/bcp.13989 -
BMJ (Clinical Research Ed.) Oct 1989
Topics: Agranulocytosis; Diuretics; Female; Humans; Metolazone; Middle Aged; Neutropenia
PubMed: 2508968
DOI: 10.1136/bmj.299.6705.981-a -
The American Journal of Case Reports Jun 2016Angiotensin-converting enzyme inhibitors are widely used drugs, and in appropriately selected patients, serious side effects are infrequent. Commonly seen side effects...
BACKGROUND
Angiotensin-converting enzyme inhibitors are widely used drugs, and in appropriately selected patients, serious side effects are infrequent. Commonly seen side effects include cough, rash, hyperkalemia, renal dysfunction, and angioedema. Historically, dose-related agranulocytosis has been associated with captopril. Benazepril, a relatively more potent angiotensin-converting enzyme inhibitor, is rarely associated with agranulocytosis.
CASE REPORT
Here, we report a case of drug-induced agranulocytosis due to benazepril, with complete recovery of white blood cell count upon discontinuation of the drug. All tests for other causes of agranulocytosis were unremarkable. This report highlights a serious and rare side effect associated with benazepril.
CONCLUSIONS
Benazepril is a commonly employed anti-hypertensive medication, and we report an unusual condition associated with this medication in order to increase vigilance among caregivers. In such cases, prompt recognition and discontinuation of the causative drug can make the difference between a recovery and a fatal outcome associated with drug-induced agranulocytosis.
Topics: Agranulocytosis; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Humans; Male; Middle Aged
PubMed: 27335175
DOI: 10.12659/ajcr.898028 -
Genes Oct 2020Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably,...
Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations ( < 1 × 10) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41-6.68, = 1.01 × 10) and rs4427239 (OR = 5.47, 95%CI: 2.81-10.65, = 5.75 × 10), of which the latter is located in the gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.
Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Biomarkers, Pharmacological; Case-Control Studies; Dipyrone; Europe; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Germany; Humans; Male; Middle Aged; Neutropenia; Retrospective Studies; Switzerland
PubMed: 33138277
DOI: 10.3390/genes11111275