Drug induced thrombocytopenia is the most common druginduced hematologic disorders, with some reports suggesting that as many as 5% of patients who receive heparin develop heparin induced thrombocytopenia. Decreased production is frequently a consequence of. Nonchemotherapy idiosyncratic druginduced neutropenia idin is a relatively rare but potentially fatal disorder that occurs in susceptible. The mechanism of neutropenia can be varied depending on the drug. It usually occurs one to two weeks after the first drug dose. Pegfilgrastim neulasta is administered as a single s.
Cytotoxic chemotherapy can cause a predictable and doserelated decrease in neutrophil count. Other causes of acquired neutropenia, such as drugs and infections, are discussed separately. Agranulocytosis is defined as an absolute neutrophil count anc drug related neutropenia hematological disorders arise through a variety of mechanisms and etiologies. No further testing is required, but other causes may need to be excluded in this time if there is a strong index of suspicion. Induced neutropeniaa survey for stockholm 19731978. The quantification of the incidence of potentially druginduced 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. Druginduced neutropenia is a potentially serious and lifethreatening adverse event that may occur secondary to therapy with a variety of agents. The primary treatment of druginduced hematologic disorders is removal of the drug in question and symptomatic support of the patient. The association between nonsteroidal antiinflammatory drugs nsaids and neutropenia is based primarily on case reports only. In drug induced neutropenia, discontinuation of known drug causes will lead to resolution of the neutropenia in 1 to 3 weeks. Daniel, pharmd, bcps, bcpp, and tonya gross, pharmd savvy psychopharmacology use of filgrastim is produced in partnership with the college. In the present paper, we report and discuss the clinical data and management of this rare disorder.
Methimazoleinduced agranulocytosis in patients with. Drug therapy plays a significant role in causing neutropenia. Management and prevention of agranulocytosis in patients. Idiosyncratic druginduced agranulocytosis idia or acute severe neutropenia is historically characterized by neutrophil count.
Druginduced neutropenia and agranulocytosis uptodate. The exact mechanism of clozapine induced neutropenia is unknown, although it is possible it stems from the drug s effect on white blood cell precursors. However, if there is a history of this reaction to a particular. Listed below are some drugs that may cause neutropenia. The commonest drugs were sulfonamides, thyreostatics and thenalidine. Pdf management of chemotherapy induced neutropenia an. Neutropenia secondary to other medications tends to be an idiosyncratic reaction either as an immune. State of art of idiosyncratic druginduced neutropenia or. Clozapine, agranulocytosis, and benign ethnic neutropenia. Managing clozapineinduced neutropenia and agranulocytosis. Lamotrigineinduced neutropenia followed by drug eruption.
Drug induced cytotoxicity affects protein synthesis or cell replication in the granulocytic precursors and is usually dose dependent. Possible mechanisms and management daniel tesfa,1 marianne keisu,2 and jan palmblad1 the incidence of drug induced neutropenia has not changed in the western hemisphere over the last 30. A severe form of neutropenia low neutrophil levels caused by a reaction to a drug. Neutropenia and agranulocytosis can also result from antibody or compliment mediated damage to the stem cells. In 84 cases the neutropenia was probably caused by drugs other than cytostatics, giving an annual incidence of 0. Druginduced neutropenia pathophysiology, clinical features. In this article, we discuss its diagnosis and management and we consider the drugs. Filgrastim was a significant advance in the management of drug induced neutropenia in the past decade, but therapy with pegfilgrastim a pegylated, longacting form of filgrastim ushers in the current decade. For example, heavy alcohol consumption can cause generalized.
The clinical data of 30 caucasian patients followed up for antithyroid drug induced neutropenia at a thirdlevel hospital are reported. Druginduced hematologic disorders can occur by two mechanisms. Neutropenia and thrombocytopenia induced by quetiapine. Antithyroid drugs methimazole induced agranulocytosis in patients with graves disease is more likely with a daily dose of 30 mg than with 15 mg takata k, kubota s, fukata s, kudo t, nishihara e, ito m, amino n, miyauchi a. Idiosyncratic druginduced neutropenia and agranulocytosis qjm. Multiple studies have evaluated the risk factors for developing rituximabinduced lateonset neutropenia. The most important series devoted to antithyroid drug induced severe neutropenia and agranulocytosis are japanese studies, almost specifically in relation to the intake of methimazole. Severe neutropenia resulting in neutropenic fever and infection can lead to hospitalization, the need for broadspectrum antibiotics, and the potential sequelae of bacteremia, and it can be fatal. Additionally, the risk is higher in certain patient populations african heritage, yemenite, west indians, and arab. In the present paper, we report and discuss the diagnosis and management of idiopathic drug induced or drug associated agranulocytosis. Possible risk factors for leukopenia and neutropenia include preexisting low white blood cell count wbc or absolute neutrophil count anc and history of drug induced leukopenia or neutropenia. Listed below are some drugs that may cause neutropenia neutrophil count druginduced neutropenia and also provide insights into future research in this realm. Drug induced cutaneous eruption briefly, drug eruption is a relatively common adverse reaction to various drugs including some psychiatric mediacations 1,2. Diagnosis and management of idiopathic druginduced.
Rituximab can cause lateonset neutropenia that may result in serious lifethreatening complications. Druginduced neutropenia if a drug cause is suspected, and if wbc severe neutropenia and unwell or febrile. To date, nonchemotherapy drug induced severe neutropenia neutrophil count of. Medication causes of neutropenia, neutropenia due to medication, drug induced neutropenia, drug induced agranulocytosis. Drug induced neutropenia is the second most common type of neutropenia and is caused by two possible mechanisms. Idiosyncratic druginduced neutropenia and agranulocytosis. Clozapine is wellknown for this side effect which is rare for other antipsychotics. The recommended criteria for diagnosing blood cytopenias and for implicating a drug as a causative agent in neutropenia are derived from an international consensus.
In some cases, people only learn they have neutropenia when they have a blood test for an unrelated reason. Neutropenia can occur at any time during the course of treatment but most commonly occurs within the first few weeks after initiation of drug therapy. Neutropenia and thrombocytopenia induced by quetiapine monotherapy. The neutropenia may be immune mediated or due to direct inhibition of the bone marrow precursors.
Druginduced neutropenia is characterized by a decline in absolute neutrophil counts precipitated by exposure to a medication. In 1980, we reported that in 347 cases of immune hemolytic anemia, approximately 12% were drug induced. The author describes the pathophysiology, incidence, and management of this adverse reaction and presents two case histories. Many drugs can cause agranulocytosis and neutropenia. Many anti neoplastic drugs cause agranulocytosis and neutropenia by bone marrow suppression. Mirtazapineinduced thrombocytopenia and neutropenia. Listed below are some drugs that may cause drug induced thrombocytopenia. Since neutropenia is frequently induced by sepsis in infants, it may be difficult to determine whether the neutropenia resulted inthe neutropenia. A complete list of drugrelated agranulocytosis case reports can be found at.
Agranulocytosis occurs in about 1% of patients taking clozapine. Druginduced neutropenia and absent abdominal reflexes 1 causes druginduced neutropenia and acute cns degeneration 1 causes druginduced neutropenia and acute cns demyelination 1 causes druginduced neutropenia and acute confusion in children 1 causes druginduced neutropenia and acute confusion in the elderly 1 causes drug induced. Four controls per case were randomly chosen, matched for age, sex, state, and year. Diagnosis and management of idiopathic druginduced and. Druginduced agranulocytosis drug and therapeutics bulletin. Druginduced neutropenia symptoms, diagnosis, treatments. Metamizole dipyrone, previously the commonest cause of drug. Special mention should be made of late onset and potentially severe neutropenia, especially following anticd52 agent therapy. Nonsteroidal antiinflammatory drugs and neutropenia. Search strategy a literature search was performed on the pubmed database. The goals of this study were to assess the incidence and risk of chemotherapy induced neutropenia, febrile neutropenia fn and dose limitations in breast cancer and lymphoma patients undergoing. The mechanisms of the neutropenia are varied and the propensity to infection depends upon the adequacy of bone marrow reserve.
A thorough laboratory workup and a detailed patient history to. Druginduced neutropenia if a drug cause is suspected, and if wbc severe neutropenia. In this chapter, we report and discuss the diagnosis and management of idiosyncratic druginduced, or drugassociated, severe neutropenia, and. Significant progress has been made in recent years in the field of idiosyncratic drug induced neutropenia, leading to an.
Druginduced neutropenia is caused by decreased production or in creased destruction of neutrophils. Either the drug itself or one of its metabolites may be the causative agent. Immune hemolytic anemia associated with drug therapy. 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. See detailed information below for a list of 4 causes of drug induced neutropenia, symptom checker, including diseases and drug side effect causes. Druginduced neutropenia is a potentially lifethreatening complication that may be seen after the use of numerous drugs, including antipsychotics, antibiotics, antithyroid agents, but most importantly, chemotherapeutic drugs. Hypersensitivity and immunemediated mechanisms have been suggested, including complementmediated toxicity and drug induced antibodies against committed stem cells, proliferating precursors, and mature blood cells 4. Druginduced neutropenia symptom checker check medical. Assessment of neutropenia approach bmj best practice. Others causes of acquired neutropenia, such as primary immune mechanisms, chemotherapy, and infections, as well as congenital neutropenia in children are discussed separately.
The highest risk categories are antithyroid medications, macrolides, and procainamides. Numerous drugs have been associated with neutropenia. The data of 30 patients with idiosyncratic antithyroid. Background severe nonchemotherapy druginduced neutropenia is a rare idiosyncratic drug reaction that is considered potentially fatal. Cases were defined as patients hospitalized with neutropenia.
Stroncek a large number of drugs have been found to cause neutropenia. The reaction may be immunemediated or result from inhibition of neutrophil production by the bone marrow. Drug induced hematological disorders can span almost the entire spectrum of hematology, affectingred cells, white cells, platelets, and the coagulation system 1. Its exact mechanism is unknown but assumed as a combination of alterations in drug metabolism, drug. Mirtazapine induced thrombocytopenia is a rare hema.