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Agranulocytosis

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Chinglung Cheung – One of the best experts on this subject based on the ideXlab platform.

  • incidence and risk estimate of drug induced Agranulocytosis in hong kong chinese a population based case control study
    Pharmacoepidemiology and Drug Safety, 2017
    Co-Authors: Chorwing Sing, Chinglung Cheung, Ian C K Wong, Bernard M Y Cheung, Johnny C Y Chan, Jody K P Chu

    Abstract:

    Purpose Drug-induced Agranulocytosis is a rare but life-threatening adverse drug reaction. Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with Agranulocytosis in Hong Kong Chinese. Methods A population-based case-control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug-induced Agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. Results 155 cases of drug-induced Agranulocytosis were identified. Mean age was 51.4 years and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person-years and the all-cause mortality of patients with drug-induced Agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of Agranulocytosis (adjusted OR 416.7, 95% Confidence Interval (CI) 51.5 – 3372.9) with an incidence of 9.2 (95% CI 6.9 – 12.1) per 10,000 users and 3.6 (95% CI 2.7 – 4.8) per 10,000 user-years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. Conclusions The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with Agranulocytosis in Hong Kong Chinese. Methods A population-based case-control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug-induced Agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. Results 155 cases of drug-induced Agranulocytosis were identified. Mean age was 51.4 years and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person-years and the all-cause mortality of patients with drug-induced Agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of Agranulocytosis (adjusted OR 416.7, 95% Confidence Interval (CI) 51.5 – 3372.9) with an incidence of 9.2 (95% CI 6.9 – 12.1) per 10,000 users and 3.6 (95% CI 2.7 – 4.8) per 10,000 user-years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. Conclusions The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common implicated drug class and carbimazole had the highest risk of Agranulocytosis.

  • hla b 38 02 01 predicts carbimazole methimazole induced Agranulocytosis
    Clinical Pharmacology & Therapeutics, 2016
    Co-Authors: Chinglung Cheung, Munir Pirmohamed, C W Sing, Clara S Tang, V K Cheng, C H Choi, C S Hung, Ey Lau, K F Lee, M W Mak

    Abstract:

    Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced Agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced Agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced Agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced Agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced Agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing Agranulocytosis in populations in which the frequency of the risk allele is high.

M M Van Der Klauw – One of the best experts on this subject based on the ideXlab platform.

  • a population based case cohort study of drug associated Agranulocytosis
    JAMA Internal Medicine, 1999
    Co-Authors: M M Van Der Klauw, R Goudsmit, M R Halie, M Vant B Veer, Rmc Herings, J H P Wilson, Bruno H Stricker

    Abstract:

    Background Agranulocytosis is a life-threatening disorder, often caused by drugs. Incidences or risks of drug-induced Agranulocytosis are not well known, since it is rare. Methods To determine the risk of drug-associated Agranulocytosis as a reason for admission to Dutch hospitals, we performed a population-based case-cohort study. Hospital discharge data came from the Dutch Centre for Health Care Information, Utrecht, which contains data on all general and university hospitals in the Netherlands. The reference cohort consisted of all persons in the catchment area of the Pharmaco Morbidity Record Linkage System (PHARMO RLS) in the Netherlands, composing a population of approximately 220,000 to 484,000 persons from 1987 through 1990. All admissions during that period with Agranulocytosis or related diagnoses were included in the study (n=923). The potential causes of Agranulocytosis were assessed in all cases classified as probable or possible Agranulocytosis. Results Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678, 108 were classified as “Agranulocytosis probable” or as “Agranulocytosis possible.” In 75 of these 108 cases, Agranulocytosis had been the reason for admission. Fifteen patients had used methimazole within 10 days before developing Agranulocytosis; 2, carbimazole; 9, sulfasalazine; 8, sulfamethoxazole-trimethoprim; 4, clomipramine hydrochloride; and 2, dipyrone with analgesics, yielding adjusted relative risks of Agranulocytosis of 114.8 (for thyroid inhibitors combined) (95% confidence interval [CI], 60.5-218.6), 74.6 (95% CI, 36.3-167.8), 25.1 (95% CI, 11.2-55.0), 20.0 (95% CI, 6.1-57.6), and 26.4 (95% CI, 4.4-11.1), respectively. Conclusions The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone combined with analgesics.

  • drug associated Agranulocytosis 20 years of reporting in the netherlands 1974 1994
    American Journal of Hematology, 1998
    Co-Authors: M M Van Der Klauw, J H P Wilson, B Ch H Stricker

    Abstract:

    In this descriptive study, all 425 reports were included concerning drug-associated Agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of Agranulocytosis or neutropenia according to previously defined criteria. Subsequently, the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports Agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports Agranulocytosis or neutropenia were unlikely. In the 13 reports of probable Agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasalazine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause Agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to

Olav Spigset – One of the best experts on this subject based on the ideXlab platform.

  • Long-term combination treatment with clozapine and filgrastim in patients with clozapine-induced Agranulocytosis.
    International Clinical Psychopharmacology, 2003
    Co-Authors: Staffan Hägg, Staffan Rosenius, Olav Spigset

    Abstract:

    Short-term treatment with granulocyte colony-stimulating factor has been successful in reducing the duration of clozapine-induced Agranulocytosis. Long-term combination treatment with filgrastim and clozapine in patients with clozapine-induced Agranulocytosis has only been described in two previous cases. We describe three patients with schizophrenia who developed granulocytopenia or Agranulocytosis during treatment with clozapine and who did not respond to other antipsychotics. The patients received long-term combination treatment with clozapine and filgrastim. Using a combination treatment with filgrastim and clozapine, the psychotic symptoms were successfully controlled and no haematological complications were observed during the follow-up periods of 11, 30 and 48 months, respectively. Our cases suggest that long-term treatment with filgrastim might be a useful, but exceptional, treatment approach in patients who have developed clozapine-induced granulocytopenia or Agranulocytosis.

  • Agranulocytosis and other blood dyscrasias associated with dipyrone metamizole
    European Journal of Clinical Pharmacology, 2002
    Co-Authors: Karin Hedenmalm, Olav Spigset

    Abstract:

    Abstract Objective. Agranulocytosis is a potentially lethal adverse drug reaction of dipyrone (metamizole). According to case-control studies, the frequency is low, approximately one per million users. The aim of the study was to describe the pattern of blood dyscrasias associated with dipyrone, identify possible risk factors and calculate the incidence of Agranulocytosis associated with dipyrone. Methods. All spontaneous reports of serious blood dyscrasias associated with dipyrone in Sweden were reviewed. The reports were scrutinised for additional information, including bone marrow findings. The reported incidence of Agranulocytosis was estimated from total prescription sales of dipyrone. Results. The reported incidence of Agranulocytosis with dipyrone in Sweden was estimated to be at least 1:1439 (95% confidence interval 1:850, 1:4684) prescriptions. Ninety-two percent of the cases of blood dyscrasias occurred during the first 2 months of treatment. Additional risk factors were identified in 36% of the patients. In a total of five cases of which four were fatal, all three haematopoieses were affected according to bone marrow sample findings. Among the fatal cases, a higher proportion had bi- or tricytopenia than among the non-fatal cases (P<0.005) Conclusion. Based on sales data and spontaneous reporting of adverse drug reactions in Sweden, the risk of Agranulocytosis with dipyrone seems to be considerably higher than the previously estimated risks. Dipyrone is also associated with other blood dyscrasias, and the prognosis for combined dyscrasias seems to be poorer than for isolated Agranulocytosis.