Druginduced agranulocytosis in the berlin casecontrol surveillance study. The majority of agranulocytosis cases are caused by drugs, including antibiotics. Huber m, andersohn f, bronder e, klimpel a, thomae m, konzen c, meyer o, salama a, schrezenmeier h, hildebrandt m, spathschwalbe e, gruneisen a, kreutz r, garbe e eur j clin pharmacol 2014 mar. Severe druginduced agranulocytosis successfully treated.
Increased risk of bacterial infection weakness chills. Objective in this article, we report and discuss the clinical presentation and management of idiosyncratic druginduced agranulocytosis neutrophil count agranulocytosis is dependent upon the severity of the signs and symptoms and associated complications, if any. Granulocyte colonystimulating factor a number of uncontrolled case studies have reported shorter recovery times compared with historic controls while others show no change with the use of granulocyte or granulocytemacrophage colonystimulating factor gcsf or gmcsf in infected patients with druginduced agranulocytosis. Idiosyncratic drug induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0. Their exact mechanisms are unknown but most appear to be immunemediated. The drug etiology of agranulocytosis and aplastic anemia. Stopping a medication that is believed to cause the disease. Drugs are the most common cause of agranulocytosis 1. We do not consider the doserelated granulocytopenia that commonly complicates. The code is valid for the year 2020 for the submission of hipaacovered transactions. Pdf agranulocytosis associated with dipyrone metamizol. The treatment for agranulocytosis depends upon whether the condition is acquired or congenital. However, only four cases of spironolactoneinduced agranulocytosis have been previously reported 36, all of which were concurrently treated with furosemide.
However, the proportion of cocaine users exposed to levamisole who might develop levamisole induced agranulocytosis, is unknown. Up to 50% of agranulocytosis may be induced by nonchemotherapy drugs, such as antithyroid agents and antimicrobial medications. Additional and relevant useful information for acquired agranulocytosis. Neutropenia and agranulocytosis can also result from antibody or compliment mediated damage to the stem cells. Agranulocytosis induced by nonchemotherapy drugs article pdf available in annals of internal medicine 1484. Case report agranulocytosis in induced tertian malaria major benjamin r. Dapsone agranulocytosis jama dermatology jama network.
Criteria for idiosyncratic druginduced agranulocytosis. Agranulocytosis management and treatment cleveland clinic. Agranulocytosis associated with cocaine use four states. Aalso called agranulocytic angina or granulocytopenia. Clinical and hematologic characteristics of phenothiazineinduced agranulocytosis suggest that the mechanisms underlying the development of this condition are related to a possible suppressive effect of phenothiazines on cell division. The doctor may tell you to stop taking the drug for a while to see if you improve. It also suggested mechanisms involving preformed blood factors, e. Idiosyncratic drug induced agranulocytosis is a disorder that preferentially affects older individuals, probably reflecting higher medication use associated with older age and the incidence is higher in women than in men. Agranulocytosis in induced tertian malaria sciencedirect. 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. Apr 27, 2020 relative lymphocytosis associated with granulocytopenia neutropenia and agranulocytosis last updated on mon, 27 apr 2020 hematology neutropenia is defined by a decrease in the number of neutrophilic granulocytes with segmented nuclei to less than 15001 1. These blood cells play a key role in the elimination of pathogens. Acquired agranulocytosis what is acquired agranulocytosis.
Agranulocytosis has been recognized as an idiosyncratic reaction to levamisole in 2. Objective in this article, we report and discuss the clinical presentation and management of idiosyncratic druginduced agranulocytosis neutrophil count cautious use of allopurinol sheng hsiang ma1 and chun hsing liao2 1department of medicine, national yangming university, taiwan 2department of internal medicine, far eastern memorial hospital, taiwan received. The mechanism of neutropenia can be varied depending on the drug. Idiosyncratic druginduced agranulocytosis or acute neutropenia. People with this condition are at very high risk of serious infections. Agranulocytosis induced by drugs other than chemotherapy frank andersohn, md. Agranulocytosis, acquired nord national organization for. Clinical presentation and management of druginduced agranulocytosis. The major histocompatibility complex region marked by hsp701 and hsp702 variants is associated with clozapine induced agranulocytosis in two different ethnic groups. In the aplastic phase of the disease a, the number of both cfugm and cluster forming cells was decreased in comparison to normal values. Association between the drb108032 histocompatibility antigen and methimazole induced. Many anti neoplastic drugs cause agranulocytosis and neutropenia by bone marrow suppression. It is a serious condition, and about 1 in 10 cases results in death. In case of sepsis, we commonly combine in first line.
The incidence of clozapine induced agranulocytosis and neutropenia in patients who received clozapine for 1, 2, 3 or 4 years in the uk and ireland between 1990 and. The prognostic value of 36 clinical and analytical parameters at diagnosis in patients with drug. You can also acquire it from certain drugs or medical procedures. Agranulocytosis can be congenital, meaning youre born with the condition. Clinical and hematologic characteristics of phenothiazine induced agranulocytosis suggest that the mechanisms underlying the development of this condition are related to a possible suppressive effect of phenothiazines on cell division. Neutrophils are a type of white blood cell that your. Chun hsing liao, department of internal medicine, section of infectious. In this setting, old age 65 years, septicemia or shock. Eight deaths due to dapsone induced agranulocytosis have been reported recently. Apparently promethazine and methdilazine do not cause agranulocytosis. Mechanism of clozapineinduced agranulocytosis springerlink.
Acquired agranulocytosis is characterized by a shortage of white blood cells in the blood. Clozapine, agranulocytosis, and benign ethnic neutropenia. Evidence for drug induction of agranulocytosis, 6 4. Idiosyncratic druginduced agranulocytosis or acute. If you are aware of a case report of nonchemotherapy druginduced agranulocytosis that 1 was published in a medical journal in english or german language, 2 fits our in and exclusion criteria see original paper, and that 3 is missing in this database, please submit the citation and a pdf version of the paper if possible to the e. A different medication may be substituted for the original. Pdf the etiology, epidemiology and management of idiosyncratic. Agranulocytosis induced by multidrug therapy in leprosy treatment. Although it was recognised as an idiosyncratic type of drug reaction more than 50 years ago, its pathogenesis is still not fully understood. The name granulocyte refers to grainlike bodies within the cell.
The symptoms of acquired agranulocytosis may subside when the causative drug is lowered in dosage or is discontinued. Diagnosis and management of idiopathic druginduced severe. Read more about symptoms, diagnosis, treatment, complications, causes and prognosis. T1 amitriptylineinduced agranulocytosis with bone marrow confirmation. 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. Deaths owing to ticlopidineinduced bone marrow suppression have been reported and have usually occurred in the setting of aplas tic anemia. Pdf agranulocytosis induced by nonchemotherapy drugs. When elderly patients are prescribed many different medications, the risk for developing serious adverse events should be kept in mind. Acquired agranulocytosis is caused by the use of a wide variety of drugs. Case fatality is around 10%,but this may depend to a large extent on the availability of prompt antibiotic treatment. Here, we report a case of severe agranulocytosis in a 96yearold. These factors may combine to further worsen the prognosis of an already severely.
Others causes of acquired neutropenia, such as primary immune mechanisms, chemotherapy, and infections, as well as congenital neutropenia in children are discussed separately. It is a severe lack of one major class of infectionfighting white blood cells. The major histocompatibility complex region marked by hsp701 and hsp702 variants is associated with clozapineinduced agranulocytosis in two different ethnic groups. Drug induced agranulocytosis study results comment. In our hospital, we commonly combine in first line therapy, new cephalosporins and. Drug induced thrombocytopenia is the most common drug induced hematologic disorder, with reports suggesting that between 0.
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. Common symptoms of acquired agranulocytosis include the following. Agranulocytosis is a rare and lifethreatening condition, with an annual incidence of 1. In our milieu, agranulocytosis attributable to metamizol is rare. Druginduced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections such as pneumonia, septicemia and septic shock in around two thirds of patients. Evidence for drug induction of aplastic anemia, 10 5. State of art of idiosyncratic druginduced neutropenia or. Agranulocytosis is a condition which is characterized by decrease in the neutrophil count below 100ml of blood. Druginduced neutropenia and agranulocytosis uptodate. In this article, we discuss its diagnosis and management and we consider the drugs most commonly involved and ways of minimising risk. Druginduced agranulocytosis drug and therapeutics bulletin.
Granulocytes include basophils, eosinophils, and neutrophils. Severe druginduced agranulocytosis successfully treated with. Criteria for idiosyncratic druginduced agranulocytosis adapted from 1 3. Geographical disparities in its risk estimate can be partly explained by differences in its patterns of use, in terms of dose. Agranulocytosis, acquired nord national organization. Patients with such severe neutropenia are likely to experience lifethreatening and sometimes fatal infections. An acute condition marked by severe depression of the bone marrow, which produces white blood cells, and by prostration, chills, swollen neck, and sore throat sometimes with local ulceration. The second goal of this work was to investigate the immune component associated with drug induced agranulocytosis by studying the response of neutrophils and the overall immune system to clozapine. Leone medical corps, army of the united states on infrequent occasions in the man agement of a large number of individuals undergoing artificially induced malaria, a profound depression of the granulocytes, in addition to the com monly seen leukopenia, may be encountered. Agranulocytosis associated with dipyrone metamizol article pdf available in european journal of clinical pharmacology 6011. Agranulocytosis is a blood disorder characterized by a marked decrease in the level of granulocytes a type of white blood cell in the blood. Another experiment showed that blood transfused from agranulocytosis patient to normal controls resulted in a rapid drop in neutrophil count 5. This multicentre, retrospective study examined possible prognostic factors by multiple logistic regression analysis in a series of 168 clinical episodes.
Request pdf on researchgate drug induced agranulocytosis druginduced agranulocytosis is relatively rare. State of art on idiosyncratic druginduced severe neutropenia and. Insights into the mechanism of druginduced agranulocytosis. Agranulocytosis is a rare condition in which your bone marrow doesnt make enough of a certain type of white cell, most often neutrophils. The mechanism of clozapine induced agranulocytosis is not clear. Agranulocytosis can be treated in a number of ways. Amitriptylineinduced agranulocytosis with bone marrow. In our hospital, we commonly combine new cephalosporins such as. Agranulocytosis definition of agranulocytosis by medical.
International agranulocytosis and aplastic anemia study iaaas reported the incidence of dipyrone induced agranulocytosis as one case in 100 userweeks. Antipsychotic drugs, central nervous system stimulants. The mechanism of clozapineinduced agranulocytosis is not clear. The following article provides information about the various treatment options available for this condition. Drug induced agranulocytosis request pdf researchgate. Au andres e, zimmer j, mecili m, weitten t, alt m, maloisel f so expert rev hematol. Agranulocytosis induced by multidrug therapy in leprosy. Agranulocytosis abnormally low levels of some white cells in the blood can occur when drugs cause injury to the bone marrow.
One of these adverse events is agranulocytosis, which, although rare, can be lifethreatening if left untreated. Investigation of the mechanisms of drug induced agranulocytosis julia ring tin ip, ph. Clozapine is an atypical antipsychotic agent that has several advantages over conventional antipsychotics, not least of which is its superior efficacy. Relative lymphocytosis associated with granulocytopenia.
Acquired agranulocytosis is a rare, druginduced blood disorder that is characterized by a severe reduction in the number of white blood cells granulocytes in the circulating blood. Agranulocytosis and aplastic anemia as drug induced diseases, 5 3. Druginduced agranulocytosis is a rare, potentially fatal idiosyncratic reaction that can occur unpredictably with a wide variety of drugs when taken in a conventional dose. Idiosyncratic druginduced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such. Diagnosis and management of idiopathic druginduced and severe. Drug induced agranulocytosis is rare, perhaps affecting a few people per million of population per.
Furosemide has been reported to be highly associated with druginduced agranulocytosis in a populationbased casecontrol study 2. Agranulocytosis induced by certain phenothiazine derivatives. Oct 25, 2012 clozapine is an atypical antipsychotic agent that has several advantages over conventional antipsychotics, not least of which is its superior efficacy. Due to difficulties accessing patients, these studies were pursued by first designing a rat model of early clozapine treatment.
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