Druginduced agranulocytosis is a rare haematological. Druginduced agranulocytosis drug and therapeutics bulletin. In this chapter, we report and discuss the diagnosis and management of idiosyncratic druginduced, or drugassociated, severe neutropenia, and. Oct 25, 2012 clozapine is an atypical antipsychotic agent that has several advantages over conventional antipsychotics, not least of which is its superior efficacy. One baczol formulation also contained metamizole or dipyrone, a nonsteroidal antiinflammatory drug formerly widely prescribed outside the united states under trade names including analgin, dipirona, novalgin, and optalgin as an analgesic and antipyretic, and banned by the fda in 1977 because of its association with agranulocytosis 6. Similarities in the pathogenesis of agranulocytosis and druginduced ancaassociated vasculitis may offer insight into an improved understanding of vasculitis and agranulocytosis. Idiosyncratic druginduced agranulocytosis or acute neutropenia. In april 2008, a clinical reference laboratory in new mexico notified the new mexico department of health nmdoh of a cluster of unexplained agranulocytosis cases confirmed by bone marrow histopathology during the preceding 2 months. Agranulocytosis induced by drugs other than chemotherapy frank andersohn, md.
This metaanalysis aimed to assess the clinical effects of gcsf and nongcsf on recovery duration in patients with atdinduced agranulocytosis by analyzing the overall clinical outcomes. Febuxostatinduced agranulocytosis in an endstage renal. Agranulocytosis article about agranulocytosis by the free. The thioamideinduced agranulocytosis in this case represented a contraindication for ongoing thioamide therapy. Agranulocytosis associated with cocaine use four states, march 2008november 2009.
Patients with neutropenia of this severity are susceptible to serious and sometimes fatal infection. Others causes of acquired neutropenia, such as primary immune mechanisms, chemotherapy, and infections, as well as congenital neutropenia in children are discussed separately. The acquired form is more common among older people, while the inherited form is more often seen in children. We studied 754 cases of atdinduced agranulocytosis reported to chugai pharmaceutical until april 2011. The primary treatment of druginduced hematologic disorders is removal of the drug in question and symptomatic support of the patient. Gestationinduced agranulocytosis has not been reported, so we present a case of gestationinduced agranulocytosis in this article. Michael dettling on genetic determinants of agranulocytosis, part of a collection of online lectures. Stopping a medication that is believed to cause the disease. Relative lymphocytosis associated with granulocytopenia. Agranulocytosis associated with cocaine use four states. If direct toxic effects of the drug or its metabolites underlie the pathogenesis of ciag, we hypothesized that metabolically competent primary pbmc cell cultures from subjects with ciag would exhibit an increased sensitivity towards czp exposure.
Druginduced agranulocytosis is related to certain classes of drugs. A populationbased casecohort study of drugassociated. In the most common clinical picture, drug induced acute agranulocytosis, the bone marrow is either poor in cells or lacks granulopoietic precursor cells aplastic state, or shows a maturation block at the myeloblastpromyelocyte stage. Links to pubmed are also available for selected references. It is a heterogeneous disorder in pathogenetic terms, not surprisingly in view of its idosyncratic nature. Furosemide has been reported to be highly associated with druginduced agranulocytosis in a populationbased casecontrol study 2. Hyperthyroidism antithyroid druginduced agranulocytosis is about 10fold more common in amiodaroneinduced thyrotoxicosis than in thyrotoxicosis due to other causes the most severe side effect of antithyroid drugs is agranulocytosis, a rare side effect that causes an increased risk of developing a serious infection. If youre taking several different drugs, you may need to stop taking them. Diagnosis and management of idiopathic druginduced severe. Druginduced neutropenia and agranulocytosis uptodate.
We studied 754 cases of atd induced agranulocytosis reported to chugai pharmaceutical until april 2011. A fatal complication of clozapine induced agranulocytosis volume 11 issue 3 brian mangan, martin j toal skip to main content accessibility help we use cookies to distinguish you from other users and to provide you with a better experience on our websites. Many drugs can cause nonchemotherapy druginduced agranulocytosis. Idiosyncratic druginduced severe neutropenia and agranulocytosis in elderly patients. Clozapineinduced agranulocytosis is associated with rare. With hyperthyroidism, the prescribed antithyroid drug therapy, suppresses the bodies ability to produce mature white blood cells, causing a drug induced agranulocytosis. The code is valid for the year 2020 for the submission of hipaacovered transactions. Analysis of physician reports of 754 patients with atd induced agranulocytosis. Antithyroid druginduced agranulocytosis, a case report. Agranulocytosis definition of agranulocytosis by the free. Antithyroid druginduced agranulocytosis is about 10fold.
There are published case reports describing a potential role for plasmapheresis to control thyroid hormone levels and thyroid storm in the preoperative management of patients with thioamideinduced agranulocytosis 11, 12. Cephalosporininduced recurrent aplastic anemia pdf. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0. Propylthiouracilinduced antineutrophil cytoplasmic. Thus, we report four observations of carbimazole druginduced hepatitis during the treatment of gravesdisease, which imputability is likely and probably an immunoallergic mechanism. The mechanism of clozapine induced agranulocytosis is not clear.
Although the disease may occur spontaneously it is usually induced by exposure to antithyroid drugs, sulfonamides, phenothiazines, chemotherapy, and radiation therapies. Vaughn williams classification of antiarrhythmic medications chart e b m c o n s u l t. It results in a severe reduction of granulocytes in the peripheral blood with an absolute neutrophil count anc of under 0. A variable mortality rate has been reported, from 6% to 20%, and is related to the duration of neutropenia. Clinical presentation and management of druginduced. The doctor may tell you to stop taking the drug for a while to see if you improve. Druginduced agranulocytosis, a severe side effect marked by a deficit or absolute lack of granulocytic white blood cells, is a rare sideeffect of the antiinflammatory drug sulphasalazine. Hyperthyroidism antithyroid druginduced agranulocytosis is about 10fold more common in amiodaroneinduced thyrotoxicosis than in thyrotoxicosis due to other causes. Timely discontinuation of the offending drug is vital in reducing endorgan damage and the need for immunosuppressive therapy in druginduced ancaassociated vasculitis. In this article, we discuss its diagnosis and management and we consider the drugs most commonly involved and ways of minimising risk. Acquired agranulocytosis is a rare, drug induced blood disorder that is characterized by a severe reduction in the number of white blood cells granulocytes in the circulating blood.
Idiosyncratic druginduced agranulocytosis or acute neutropenia is a rare disorder. With hyperthyroidism, the prescribed antithyroid drug therapy, suppresses the bodies ability to produce mature white blood cells, causing a druginduced agranulocytosis. Drug induced agranulocytosis is a rare, potentially fatal idiosyncratic reaction that can occur unpredictably with a wide variety of drugs when taken in a conventional dose. If a drug needed for another condition causes agranulocytosis, your doctor may prescribe a substitute treatment.
If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Drugs are the most common cause of agranulocytosis 1. The most important managements of druginduced agranulocytosis are to identify the culprit drug, to withdraw this agent, and to give broadspectrum antibiotics for those with infection. Full text full text is available as a scanned copy of the original print version. Request pdf idiosyncratic druginduced agranulocytosis. The exact frequency of the condition is not known, but the number of cases is estimated at 1 million to 3.
Get a printable copy pdf file of the complete article 330k. Agranulocytosis is condition in which the bone marrow is not producing adequate amounts of neutrophils. The primary treatment of drug induced hematologic disorders is removal of the drug in question and symptomatic support of the patient. Get a printable copy pdf file of the complete article 330k, or click on a page image below to browse page by page. The clinical characteristics of the 55 patients with atdinduced agranulocytosis and pancytopenia are shown in table 1. Agranulocytosis is a blood disorder characterized by a marked decrease in the level of granulocytes a type of white blood cell in the blood. To determine the risk of drugassociated agranulocytosis as a reason for admission to dutch hospitals,weperformedapopulationbasedcasecohortstudy. In our case, before the initiation of febuxostat, her wbc was normal and agranulocytosis developed 2. Neutrophils are a type of white blood cell that your. Although antithyroid drug atdinduced hematopoietic damage is a significant concern, it has not been comprehensively investigated.
Be alert for signs of agranulocytosis fever, sore throat, mucosal lesions, signs of infection, aplastic anemia unusual fatigue, weakness, dizziness, pallor, thrombocytopenia bruising, nose bleeds, bleeding gums, or fatigue and poor health that might be due to other anemias and blood dyscrasias. Clinical courses of patients with atdinduced agranulocytosis and pancytopenia. Severe druginduced agranulocytosis successfully treated with. May 01, 2007 case reports cannot provide rates of druginduced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes. Criteria for idiosyncratic druginduced agranulocytosis adapted from. Nov 24, 2016 the estimated frequency of agranulocytosis is 1.
We aimed to identify genetic variants associated with antithyroid druginduced. Idiosyncratic drug induced agranulocytosis diag is an adverse reaction to drugs due to abnormal susceptibility, peculiar to the individual. To determine the risk of drug associated agranulocytosis as a reason for admission to dutch hospitals,weperformedapopulationbasedcasecohortstudy. Many drugs can cause agranulocytosis and neutropenia by bone marrow. Diagnosis of atdinduced agranulocytosis was made when patients showed a granulocyte count of less than 500. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection. Genomewide association studies gwass in ethnic chinese people in taiwan and hong kong have shown an association between agranulocytosis induced by antithyroid drugs and the hla alleles hlab38. State of art of idiosyncratic druginduced neutropenia or. She was diagnosed with drug induced agranulocytosis presumably from antibiotics used with mild pneumonia and admitted to an isolated room. Get a printable copy pdf file of the complete article 207k, or click on a page image below to browse page by page.
Agranulocytosis can be treated in a number of ways. Mutations in the human neutrophil elastase gene ela2, causing increased intracellular concentration of this serine protease, inhibits neutrophil differentiation in severe congenital neutropenia scn. Pdf the etiology, epidemiology and management of idiosyncratic. Candesartan, lansoprazole, amlodipine, and celecoxib were discontinued because they are also known to cause agranulocytosis. Agranulocytosis management and treatment cleveland clinic. Incidencesorrisksofdrug induced agranulocytosis are not well known, since it is rare. Agranulocytosis associated with dipyrone metamizol. Hyperthyroidism antithyroid drug induced agranulocytosis is about 10fold more common in amiodarone induced thyrotoxicosis than in thyrotoxicosis due to other causes. Nonchemotherapy idiosyncratic druginduced neutropenia idin is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an incidence of 2. Druginduced hematologic disorders can occur by two mechanisms.
Can mutations in ela2, neutrophil elastase expression or. A fatal complication of clozapine induced agranulocytosis. Antithyroid activity and toxicity of mercazole and neomercazole. Over time, we have observed a decrease in case fatalities in reposts of drug. Dec 08, 2017 chemotherapy druginduced neutropenia has a very high incidence in oncology patients. Case fatality may be decreasing over time with the availability of better treatment. Almost all classes of medicines have been implicated in agranulocytosis. The incidence of druginduced immune thrombocytopenia and neutropenia is quite well documented 10 to 18 and 2 to 15 cases per million, respectively, 1, 3 but there are no good data for diiha. Institutional repository uin syarif hidayatullah jakarta. Granulocytecolonystimulating factor gcsf is highly beneficial as a general treatment for antithyroid drug atdinduced agranulocytosis. Incidencesorrisksofdruginduced agranulocytosis are not well known, since it is rare. Get a printable copy pdf file of the complete article 1. Druginduced thrombocytopenia is the most common druginduced hematologic disorders, with some reports suggesting that as many as 5% of patients who receive heparin develop heparininduced thrombocytopenia. Table of contents pdf file for saving and printing.
However, the proportion of cocaine users exposed to levamisole who might develop levamisoleinduced agranulocytosis, is unknown. Capitals indicate lifethreatening, underlines indicate most frequent. Hyperthyroidism antithyroid druginduced agranulocytosis is about 10fold more common in amiodaroneinduced thyrotoxicosis than in thyrotoxicosis due to other causes the most severe side effect of antithyroid drugs is agranulocytosis, a rare side effect that causes an increased risk of developing. Druginduced agranulocytosis is a potentially lifethreatening adverse reaction. Our study design consisted of looking for genetic associations with ciag across the minor allele frequency spectrum.
However, only four cases of spironolactoneinduced agranulocytosis have been previously reported 36, all of which were concurrently treated with furosemide. Clinicians should be aware of the possible relationship between levamisoleassociated agranulocytosis and use of cocaine, and possibly heroin, and should obtain a drug history in all potential cases routinely. Populationbased druginduced agranulocytosis hematology. Absolute neutrophil count anc is the laboratory parameter for monitoring patients for clozapineinduced. Antithyroid druginduced agranulocytosis by elizabeth spears. Oct 06, 2016 treatment if agranulocytosis has arisen from an underlying illness, that condition will be treated. Idiosyncratic druginduced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new. It occurs es pecially in association with the use of antithyroid drugs, metamizole, aminopyrine and clo zapine. Get a printable copy pdf file of the complete article 497k. Nonchemotherapy druginduced agranulocytosis annals of. People with this condition are at very high risk of serious infections. Previous case reports have shown that the use of granulocyte macrophage. As in neutropenia related to chemotherapy, modern management of such event may. Full text is available as a scanned copy of the original print version.
Many drugs can cause agranulocytosis and neutropenia. The number of reports increased every year until 2003, probably due to a rise in physician awareness of drug complications. The treatment for agranulocytosis depends upon whether the condition is acquired or congenital. Agranulocytosis induced by nonchemotherapy drugs annals of. Median intervals between initiation of atd therapy and the onset of agranulocytosis and pancytopenia were 69 d range, 11233 d and 41 d range. Indeed, one drug might cause agranulocytosis by different mechanisms in different patients. Druginduced agranulocytosis occurs most commonly in females and the elderly i. Many anti neoplastic drugs cause agranulocytosis and neutropenia by bone marrow suppression. The mechanism of neutropenia can be varied depending on the drug. Alternatively, you can download the file locally and open with any standalone pdf reader. Agranulocytosis occurs among all age groups and in all racial groups.
Case reports cannot provide rates of druginduced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes. Agranulocytosis is a rare condition in which your bone marrow doesnt make enough of a certain type of white cell, most often neutrophils. Idiosyncratic druginduced agranulocytosis is a potential adverse event of most drugs, rare but lifethreatening. Neutropenia and agranulocytosis can also result from antibody or compliment mediated damage to the stem cells. Nonchemotherapy drug induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0. The differential diagnosis of pure agranulocytosis versus aplasias of several cell lines is outlined on. The following article provides information about the various treatment options available for this condition. Agranulocytosis, acquired nord national organization for. Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous leukopenia lowered white blood cell count, most commonly of neutrophils, and thus causing a neutropenia in the circulating blood. Drug induced thrombocytopenia is the most common drug induced hematologic disorders, with some reports suggesting that as many as 5% of patients who receive heparin develop heparin induced thrombocytopenia. Agranulocytosis induced by nonchemotherapy drugs annals. Over the last 20 years, the incidence of idiosyncratic drug induced agranulocytosis or acute neutropenia has remained stable at 2.
Carbimazole druginduced hepatitis during treatment of. The quantification of the incidence of potentially drug induced agranulocytosis in general, and in particular its association with single drugs, requires studies on large populations and the use of strict epidemiological methodology to prevent reporting of grossly biased results. We did a gwas in 234 european adults with any nonchemotherapy druginduced agranulocytosis absolute neutrophil count. How to approach druginduced agranulocytosis in icu mahant s. Find support for a specific problem on the support section of our website. In europe, the annual incidence of idiosyncratic druginduced agranulocytosis. Genetic variants associated with antithyroid druginduced. It is a severe lack of one major class of infectionfighting white blood cells.
Anc is more relevant to druginduced neutropenia than white blood cell wbc count anc may also be calculated using the following formula. In at least 75% of affected patients, the neutrophil count is almost. Mechanism of clozapineinduced agranulocytosis springerlink. Agranulocytosis is a lifethreatening disorder,oftencausedbydrugs. Analysis of physician reports of 754 patients with atdinduced agranulocytosis. The prevalence of agranulocytosis and related death in. Sex agranulocytosis occurs slightly more frequently in women than in men, possibly because of their increased rate of medication usage. A more serious adverse affect of drug therapy would be agranulocytosis. The name granulocyte refers to grainlike bodies within the cell. Thyroidectomy for the treatment of graves thyrotoxicosis. Drug induced hematologic disorders can occur by two mechanisms. Jcm free fulltext state of art of idiosyncratic drug. Please select some articleschapters to export citations. Pdf agranulocytosis associated with dipyrone metamizol.
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