ABSTRACT
Vemurafenib is an oral BRAF kinase inhibitor approved since 2012 for the treatment of patients with unresectable or metastatic melanoma with BRAF mutations. Vemurafenib also demonstrated efficacy for patients with hairy cell leukemia genetically characterized by BRAF mutation. Here, we report the case of a 38-year-old female patient without any previous medical history who experienced agranulocytosis associated with erythrodermia after vemurafenib initiation for the treatment of hairy cell leukemia. Agranulocytosis was confirmed with bone marrow examination. Vemurafenib was considered the most probable drug responsible for this agranulocytosis and was thus stopped. We observed a full neutrophils recovery 10 days after vemurafenib cessation without any haematopoietic growth factors. A bone marrow biopsy performed 1 month after aplasia ending showed a good partial response with less than 5% of hairy cells remaining. To our knowledge, this is the first case ever described by vemurafenib-induced agranulocytosis. Thus, physicians should be warned about this risk given the growing number of patients treated with vemurafenib.
Subject(s)
Agranulocytosis/physiopathology , Leukemia, Hairy Cell/drug therapy , Vemurafenib/administration & dosage , Withholding Treatment/statistics & numerical data , Adult , Agranulocytosis/chemically induced , Female , Humans , Leukemia, Hairy Cell/pathology , Prognosis , Vemurafenib/adverse effectsSubject(s)
Agranulocytosis/chemically induced , Dipyrone/adverse effects , Fournier Gangrene/chemically induced , Agranulocytosis/diagnostic imaging , Agranulocytosis/physiopathology , Child , Drug-Related Side Effects and Adverse Reactions , Fournier Gangrene/diagnostic imaging , Fournier Gangrene/physiopathology , Humans , MaleABSTRACT
RATIONALE: Pregnancy is a complicated physiological process. Physiological leukocytosis often takes place and it is primarily related to the increased circulation of neutrophils, especially during the last trimester of pregnancy. Noncongenital agranulocytosis during pregnancy is rare and reported only occasionally, while in most of the cases, the agranulocytosis has already occurred prior to pregnancy or induced by identified factors such as antibiotics, antithyroid agents, or cytotoxic agents. Gestation-induced agranulocytosis has not been reported, so we present a case of gestation-induced agranulocytosis in this article. PATIENTS CONCERN: In this case, we present a Chinese woman (aged 25) in her 38th week of the first gestation who had the complication of agranulocytosis. No abnormality was detected in regular examinations before pregnancy and in the first trimester. Since the last trimester of pregnancy, the patient began to suffer from agranulocytosis and intermittent fever, the maximum being temperature 38.8°C. At admission, the neutrophil granulocytes were 0.17â×â10âL and the bone marrow biopsy showed that agranulocytosis was detected, but the levels of red blood cell and megalokaryocyte were normal. In addition, antinuclear antibodies were detected at a dilution of 1:40, but anti-dsDNA, antiphospholipid antibody, and neutrophil granulocyte antibody were negative. DIAGNOSES: The patient was empirically treated as having pneumonia. INTERVENTIONS: We tried to use granulocyte colony-stimulating factor, γ-globulin, glucocorticoids, antibiotics, and antifungi agents to treat the patient, but her symptoms were not alleviated until the patient had a cesarean section. OUTCOMES: After 24 hours of cesarean section, the temperature and neutrophil granulocyte returned to normal. After a year of follow-up, we found that the patient and the baby were healthy. LESSONS: Agranulocytosis during pregnancy seems to be associated with immunosuppression induced by immunoregulations and termination of pregnancy may be effective for refractory pregnancy complicated with agranulocytosis, but further studies are needed to confirm this.
Subject(s)
Agranulocytosis/complications , Pregnancy Complications, Hematologic/diagnosis , Adult , Agranulocytosis/physiopathology , Anti-Bacterial Agents/therapeutic use , Cesarean Section , Female , Fever/complications , Humans , Pregnancy , Pregnancy Complications, Hematologic/physiopathologyABSTRACT
The antithyroid agents (carbimazole, methimazole, thiamazole, propylthiouracil and benzylthiouracile) are the drug class that is associated with a high risk of agranulocytosis. Acute and profound (<0.5×10(9)/L) isolated neutropenia occurring in a subject treated with antithyroid agents should be considered as a drug-induced agranulocytosis, until proven otherwise. The clinical spectrum ranges from discovery of acute severe but asymptomatic neutropenia, to isolated fever, localized infections (especially ear, nose and throat, or pulmonary) or septicemia. With an optimal management (discontinuation of antithyroid agents, antibiotics in the presence of fever or a documented infection, or use of hematopoietic growth factor) the current mortality is close to 2%.
Subject(s)
Agranulocytosis/chemically induced , Antithyroid Agents/adverse effects , Agranulocytosis/physiopathology , Agranulocytosis/therapy , Anti-Bacterial Agents/therapeutic use , Disease Management , HumansABSTRACT
In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of deferoxamine, suggesting that this drug is an alternative option in cases in which deferoxamine and deferasirox are contraindicated.
Subject(s)
Deferoxamine/administration & dosage , Iron Chelating Agents/administration & dosage , Iron Overload/therapy , Pyridones/administration & dosage , beta-Thalassemia/therapy , Adult , Agranulocytosis/chemically induced , Agranulocytosis/physiopathology , Arthralgia/chemically induced , Arthralgia/physiopathology , Chelation Therapy/methods , Deferiprone , Deferoxamine/adverse effects , Female , Ferritins/metabolism , Humans , Iron Chelating Agents/adverse effects , Iron Overload/etiology , Iron Overload/metabolism , Iron Overload/mortality , Linear Models , Male , Middle Aged , Neutropenia/chemically induced , Neutropenia/physiopathology , Pyridones/adverse effects , Survival Analysis , Transfusion Reaction , beta-Thalassemia/metabolism , beta-Thalassemia/mortality , beta-Thalassemia/pathologyABSTRACT
Drug-induced agranulocytosis is a severe complication that has been implicated with most classes of medications. Medications such as clozapine, trimethoprim-sulfamethoxazole and methimazole have been more commonly associated with agranulocytosis than other agents. Although the pathogenesis isn't fully elucidated, it appears to be two-fold with a direct toxicity to the myeloid cell line and immune-mediated destruction. Patients may be asymptomatic at the time neutropenia is discovered or may present with more severe complications such as sepsis. In approximately 5% of cases drug-induced agranulocytosis may be fatal. Management of drug-induced agranulocytosis includes the immediate discontinuation of the offending medication, initiation of broad-spectrum antibiotics and consideration of the use of granulocyte colony-stimulating factors in high-risk patients.
Subject(s)
Agranulocytosis/chemically induced , Agranulocytosis/physiopathology , Drug-Related Side Effects and Adverse Reactions/physiopathology , Agranulocytosis/drug therapy , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/adverse effects , Antithyroid Agents/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Myeloid Cells/drug effects , Neutropenia/chemically induced , Psychotropic Drugs/adverse effectsABSTRACT
PURPOSE OF THE STUDY: To analyze complications of the pulmonary artery catheterization in patients with blood diseases. MATERIALS AND METHODS: 93 cases of pulmonary artery catheterization in patients with blood diseases were included in the retrospective study. RESULTS: Indications for pulmonary artery catheterization were septic shock (78.5%) and acute respiratory failure (21.5%). In 31 cases (33.3%) pulmonary artery catheterization was performed in conditions of agranulocytosis and in 81 cases (87%) in conditions of thrombocytopenia (platelets median 43 x 109 per liter minimal 7 x 109, maximal 150 x 109 per liter). Patients received transfusions of platelets in case of thrombocytopenia less than 30 x 109 per liter. Early complications of pulmonary artery catheterization occurred in 5 patients with thrombocytopenia (5.4%), the complications was connected with bleeding (hematoma, bleeding from place of puncture, lung bleeding) and mechanical (arterial puncture, pneumothorax, hemothorax). Number of attempts of the central vein catheterization was risk factor the complications. The frequency of catheter-associated sepsis was 5.89 cases each 1000 catheter-days and the frequency of infections of the soft tissues was 9.78 cases each 1000 catheter-days. Catheter-associated infection complications occurred in cases of catheter use over 5 days. Catheter-associated sepsis occurred in 2 of 3 patients with agranulocytosis. Other complications included intermittent arrhythmias during catheter moving in the heart chambers (58), catheter balloon rupture (4), and thrombosis of catheter lumen (3). CONCLUSIONS: Pulmonary artery catheterization can be used in patients with blood diseases and first of all in cases of septic shock and acute respiratory failure. Alternative less invasive methods of monitoring should be used in patients with agranulocytosis.
Subject(s)
Catheter-Related Infections/epidemiology , Catheterization, Swan-Ganz/methods , Hematologic Diseases/physiopathology , Sepsis/epidemiology , Adult , Aged , Agranulocytosis/physiopathology , Catheterization, Central Venous/methods , Catheterization, Swan-Ganz/adverse effects , Female , Humans , Male , Middle Aged , Respiratory Insufficiency/therapy , Retrospective Studies , Risk Factors , Sepsis/etiology , Shock, Septic/therapy , Thrombocytopenia/physiopathology , Young AdultABSTRACT
BACKGROUND: Agranulocytosis is a serious adverse effect of antithyroid drugs (ATDs) and mainly develops within three months after the start of uninterrupted ATD treatment. Agranulocytosis can also develop for the first time after interruption and subsequent resumption of the same ATD treatment. However, little is known with regard to agranulocytosis that develops after resumption of the same ATD treatment. OBJECTIVES: We investigated the characteristics of patients who developed agranulocytosis during their second or later course of ATD treatment. METHODS: A total of 81 patients at our hospital were diagnosed with ATD-induced agranulocytosis. In 14 of the cases (methimazole (MMI), n=10; propylthiouracil (PTU), n=4), the agranulocytosis developed for the first time in the context of the second or later course of treatment with the same ATD; those patients were designated the "resumed group." The 35 patients (MMI, n=28; PTU, n=7) who developed agranulocytosis during their first uninterrupted course of ATD therapy were designated the "first group." RESULTS: The median total duration of ATD treatment before the diagnosis of agranulocytosis was 559 days (range 86-1775 days), and the median interval between the final day of the previous course and the first day of the course in which agranulocytosis was diagnosed was 916.5 days (range 153-8110 days). There were no cases in which agranulocytosis developed when treatment with the same ATD was resumed after discontinuation for less than five months. The difference between the start of ATD treatment in the course in which agranulocytosis was diagnosed and the time interval at which agranulocytosis was diagnosed was similar when comparing the first group and the resumed group (39 (20-98) days in the first group vs. 32.5 (21-95) days in the resumed group; n.s.). There were no significant differences between the groups in terms of granulocyte count at the time agranulocytosis was diagnosed, mortality rate, or the interval between the diagnosis of agranulocytosis and recovery. CONCLUSIONS: When ATD treatment is resumed, patient follow-up is essential in order to monitor for the development of agranulocytosis.
Subject(s)
Agranulocytosis/chemically induced , Antithyroid Agents/adverse effects , Graves Disease/drug therapy , Methimazole/adverse effects , Propylthiouracil/adverse effects , Adolescent , Adult , Aged , Agranulocytosis/blood , Agranulocytosis/mortality , Agranulocytosis/physiopathology , Antithyroid Agents/therapeutic use , Drug Monitoring , Electronic Health Records , Female , Granulocytes/drug effects , Hospitals, Urban , Humans , Japan , Leukopoiesis/drug effects , Male , Methimazole/therapeutic use , Middle Aged , Propylthiouracil/therapeutic use , Time Factors , Young AdultABSTRACT
INTRODUCTION: Afebrile neutropenia with an absolute neutrophil count (ANC) of zero in a nonimmunocompromised individual is unusual. Outlined is a case of agranulocytosis likely due to levamisole laced cocaine. Given recent publications in the news media and medical journals, this is a pertinent issue for primary care providers. CASE: A 57-year-old female presented with painful bowel movements and difficulty eating. Physical examination revealed two exquisitely tender ulcerated lesions on her lower lip and anus. Laboratory data revealed an ANC of 0 and urine drug screen positive for cocaine. She was prophylaxed with acyclovir, diflucan, and ciprofloxacin, and was started on granulocyte colony stimulating factor for four days. Her ANC normalized, but the cause of her severe neutropenia remained unclear. DISCUSSION: Levamisole is a veterinary antihelminthic used for treatment of rheumatoid arthritis and colorectal cancer in humans. 88% of regional cocaine samples are testing positive for levamisole, which is thought to potentiate cocaine's effects but can also cause agranulocytosis. CONCLUSIONS: Our patient did not fit the clinical picture for malignancy, viral infection, or bone marrow pathology. Given the high rate of levamisole adulterated cocaine and an otherwise negative work-up, this is the most likely explanation for her agranulocytosis.
Subject(s)
Agranulocytosis/chemically induced , Cocaine-Related Disorders/etiology , Drug Contamination , Levamisole/adverse effects , Agranulocytosis/drug therapy , Agranulocytosis/physiopathology , California , Female , Humans , Middle AgedABSTRACT
OBJECTIVE: Granulocytopenia frequently occurs in alcohol abusers with severe bacterial infection, which strongly correlates with poor clinical outcome. Knowledge of the molecular mechanisms underlying the granulopoietic response to bacterial infection remains limited. This study investigated the involvement of stem cell antigen-1 expression by granulocyte lineage-committed progenitors in the granulopoietic response to septicemia and how alcohol affected this response. DESIGN: : Laboratory investigation. SETTING: University laboratory. SUBJECTS: Male Balb/c mice. INTERVENTIONS: Thirty mins after intraperitoneal injection of alcohol (20% ethanol in saline at 5 g of ethanol/kg) or saline, mice received an intravenous Escherichia coli challenge. MEASUREMENTS AND MAIN RESULTS: E. coli septicemia activated stem cell antigen-1 expression by marrow immature granulocyte differentiation antigen-1 precursors which correlated with an increase in proliferation, granulocyte macrophage colony-forming unit production, and expansion of this granulopoietic precursor cell pool. Acute alcohol treatment suppressed stem cell antigen-1 activation and inhibited the infection-induced increases in proliferation, granulocyte macrophage colony-forming unit production, and expansion the of immature granulocyte differentiation antigen-1 precursor cell population. Consequently, recovery of the marrow mature granulocyte differentiation antigen-1 cell population after E. coli challenge was impaired. Stem cell antigen-1 was induced in sorted granulocyte differentiation antigen-1, stem cell antigen-1' cells by lipopolysaccharide-stimulated C-Jun kinase activation that was also inhibited by alcohol. Furthermore, stem cell antigen-1 knockout mice failed to expand the marrow immature granulocyte differentiation antigen-1 cell pool and demonstrated fewer newly produced granulocytes in the circulation after the E. coli challenge. CONCLUSIONS: Alcohol suppresses the stem cell antigen-1 response in granulocyte lineage-committed precursors and restricts granulocyte production during septicemia, which may serve as a novel mechanism underlying impaired host defense in alcohol abusers.
Subject(s)
Agranulocytosis/chemically induced , Antigens, Ly/physiology , Ethanol/pharmacology , Membrane Proteins/physiology , Sepsis/immunology , Agranulocytosis/metabolism , Agranulocytosis/physiopathology , Animals , Blotting, Western , Bone Marrow Cells/physiology , Escherichia coli Infections/immunology , Flow Cytometry , Granulocytes/drug effects , Granulocytes/immunology , Male , Membrane Proteins/antagonists & inhibitors , Mice , Mice, Inbred BALB CABSTRACT
Phenytoin, one of the most common antiepileptic drugs, is a major cause of antiepileptic drug hypersensitivity syndrome (AHS), which is a rare but potentially fatal complication. We herein report a 5-year-old boy who developed unexpected agranulocytosis with fever approximately one week after recovering from the typical symptoms of AHS, characterized by fever, rash, lymphadenopathy, and hepatitis, but lacking eosinophilia or lymphocytosis. High-dose steroid therapy for the former symptoms of AHS, and immunoglobulin, granulocyte colony-stimulating factor, and cefepime for the latter agranulocytosis were successfully performed. This unexpected progression from AHS to agranulocytosis shortly after recovering from the former should be recognized as another risk of AHS, possibly leading to a life-threatening condition.
Subject(s)
Agranulocytosis/chemically induced , Agranulocytosis/physiopathology , Anticonvulsants/adverse effects , Drug Hypersensitivity/complications , Drug Hypersensitivity/physiopathology , Phenytoin/adverse effects , Agranulocytosis/drug therapy , Anti-Bacterial Agents/administration & dosage , Cefepime , Cephalosporins/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/physiopathology , Child, Preschool , Disease Progression , Drug Hypersensitivity/drug therapy , Epilepsy/drug therapy , Exanthema/chemically induced , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunosuppressive Agents/administration & dosage , Lymphatic Diseases/chemically induced , Lymphatic Diseases/drug therapy , Lymphatic Diseases/physiopathology , Male , Risk Factors , Steroids/administration & dosage , Treatment OutcomeSubject(s)
Agranulocytosis/chemically induced , Antineoplastic Agents/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Adult , Agranulocytosis/physiopathology , Benzamides , Female , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complicationsABSTRACT
UNLABELLED: Congenital neutropenia in man was first reported 50 years ago by the Swedish paediatrician Rolf Kostmann. He coined the term "infantile genetic agranulocytosis" for this condition, which is now known as Kostmann syndrome. Recent studies have demonstrated a lack of antibacterial peptides and severe periodontitis in these patients despite recombinant growth factor treatment. Moreover, an increased degree of apoptosis of myeloid progenitor cells in the bone marrow has been shown. CONCLUSION: Future studies should aim to clarify the underlying molecular genetic defect in Kostmann syndrome.
Subject(s)
Agranulocytosis/history , Neutropenia/history , Agranulocytosis/genetics , Agranulocytosis/physiopathology , History, 20th Century , Humans , Neutropenia/congenital , SwedenABSTRACT
The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.
Subject(s)
Agranulocytosis/drug therapy , Amphotericin B/pharmacology , Aspergillosis, Allergic Bronchopulmonary/drug therapy , Administration, Inhalation , Aerosols , Agranulocytosis/complications , Agranulocytosis/physiopathology , Amphotericin B/chemistry , Amphotericin B/therapeutic use , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillosis, Allergic Bronchopulmonary/complications , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/isolation & purification , Disease Models, Animal , Female , Humans , Lung/drug effects , Lung/metabolism , Lung/pathology , Microbial Sensitivity Tests/methods , Particle Size , Product Surveillance, Postmarketing/methods , Pulmonary Surfactants/chemistry , Pulmonary Surfactants/pharmacology , Pulmonary Surfactants/therapeutic use , Rats , Specific Pathogen-Free Organisms , Survival Analysis , Time FactorsABSTRACT
Se estudian las alteraciones cuantitativas de los granulocitos, adquiridas y congénitas. Dentro del grupo de la neutropenias congénitas se describen la neutropenia cíclica, la neutropenia congénita severa y el síndrome de Schwasman-Diamond (AU)
Quantitative alterations of acquired and congenital granulocytes are studied. Within the group of congenital neutropenias, cyclic neutropenia, severe congenital neutropenia and Schwasman-Diamond syndrome are described (AU)
Subject(s)
Humans , Male , Female , Child , Neutropenia/complications , Neutropenia/epidemiology , Risk Factors , Agranulocytosis/complications , Agranulocytosis/epidemiology , Infections/complications , Infections/epidemiology , Malabsorption Syndromes/complications , Malabsorption Syndromes/epidemiology , Agranulocytosis/physiopathology , Neutrophils/pathology , Neutropenia/classification , Neutropenia/physiopathology , Agranulocytosis/chemically induced , Malabsorption Syndromes/etiology , Malabsorption Syndromes/physiopathologyABSTRACT
BACKGROUND: Dipyrone is a pyrazolone derivative used as an analgesic and antipyretic. Agranulocytosis, dipyrone's most serious and potentially fatal adverse effect, has led to its withdrawal in several countries. However, agranulocytosis is subject to geographical variability, ratio with at risks ranging from 0.8-23.7. In many countries dipyrone is still widely used in adults and children and even as an over-the-counter (OTC) preparation. Information on the effects of dipyrone overdose is scanty. OBJECTIVE: To determine the demographic and clinical characteristics of dipyrone overdose. METHODS: Retrospective review of prospectively collected poison center data on acute exposure to dipyrone over a three-year period. The data were subjected to descriptive analysis. Mann-Whitney test and Chi-square analysis were performed where relevant. RESULTS: A total of 243 records met the inclusion and exclusion criteria. Median age was 17y (4m-83y), median amount 5 g (250 mg-45 g), and median time to consultation was 2 h (5 min-48 h). Toxic events (49) occurred in 39 (16%) patients; 57% of these were gastrointestinal and all were mild. Time to consultation was longer in the symptomatic patients (4 h vs. 1.5 h, respectively, p=0.001) and in children (8 h vs. 3.5 h in adults). Suicidal patients ingested significantly larger amounts (8 g vs. 3.7 g, respectively, p=0.001), as did patients with gastrointestinal symptomatology (7.5 g vs. 5 g in asymptomatics, p=0.001). No agranulocytosis was reported. DISCUSSION: Dipyrone overdose is associated with mild, mainly gastrointestinal toxicity; this was noted at a median dose of 7.5 g. Early gastrointestinal decontamination may have prevented toxicity. The suggested treatment includes gastrointestinal decontamination (if <1 h since ingestion) and supportive measures.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/poisoning , Dipyrone/poisoning , Adolescent , Adult , Aged , Aged, 80 and over , Agranulocytosis/chemically induced , Agranulocytosis/physiopathology , Child , Child, Preschool , Drug Overdose , Female , Gastrointestinal Diseases/chemically induced , Humans , Infant , Israel/epidemiology , Male , Middle Aged , Poison Control Centers , Retrospective Studies , Suicide, Attempted/statistics & numerical dataABSTRACT
This retrospective study was aimed at revealing the incidence of normal white blood cell (WBC) count agranulocytosis in patients treated with antithyroid drugs (ATDs). From January 1975 to December 2001, 109 patients (0.35%) presented with ATD-induced agranulocytosis at our clinic. In 18 patients (16.5%), the WBC count exceeded 3.0 x 10(9)/L at the onset of agranulocytosis. Ten showed a downward trend in WBC count (3.0-3.9 x 10(9)/L) after the initiation of ATDs. Four had symptoms of infection. In the remaining 4 patients, routine WBC and granulocyte count monitoring detected an agranulocytosis. During the first 3 months of ATD treatment, 3347 patients (10.9%) had WBC count 3.0-3.9 x 10(9)/L even once with no symptom and normal granulocyte count and 26672 patients had WBC count >or= 4.0 x 10(9)/L with no symptom and normal granulocyte count. When agranulocytosis was found, twelve patients with normal WBC count agranulocytosis (0.36%) had WBC count 3.0-3.9 x 10(9)/L with no symptom, whereas only 2 patients with agranulocytosis (0.008%) had WBC count >or= 4.0 x 10(9)/L with no symptom. In conclusion, clinicians should take normal WBC count agranulocytosis into consideration at least during the first 3 months of antithyroid drug therapy, especially when WBC count is 3.0-3.9 x 10(9)/L.
Subject(s)
Agranulocytosis/blood , Agranulocytosis/chemically induced , Antithyroid Agents/adverse effects , Adult , Agranulocytosis/physiopathology , Antithyroid Agents/therapeutic use , Female , Granulocytes/pathology , Graves Disease/drug therapy , Humans , Leukocyte Count , Male , Middle Aged , Retrospective StudiesABSTRACT
Agranulocytosis is a life-threatening disorder in any age, but particularly so in elderly patients who are receiving, on average, a larger number of drugs than younger patients. Drug-induced agranulocytosis still remains a rare event, with an annual incidence rate of approximately 3-12 cases per million population. This disorder frequently occurs as an adverse reaction to drugs, particularly antibacterials, antiplatelet agents, antithyroid drugs, antipsychotics or antiepileptic drugs, and NSAIDs. Although patients experiencing drug-induced agranulocytosis may initially be asymptomatic, the severity of the neutropenia usually translates into the onset of severe sepsis that requires intravenous broad-spectrum antibacterial therapy. In this setting, haematopoietic growth factors have been shown to shorten the duration of neutropenia. Thus, with appropriate management, the mortality rate of idiosyncratic drug-induced agranulocytosis is now 5-10%. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.
Subject(s)
Agranulocytosis/chemically induced , Aged , Agranulocytosis/physiopathology , Agranulocytosis/prevention & control , Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antineoplastic Agents/adverse effects , Antipsychotic Agents/adverse effects , Antithyroid Agents/adverse effects , Diagnosis, Differential , Humans , Neutropenia/chemically induced , Platelet Aggregation Inhibitors/adverse effectsABSTRACT
Aerococcus viridans, a catalase-negative gram-positive coccus rarely causing bacteremia, was isolated from blood cultures of a 52-yr-old man under the granulocytopenic condition. The isolate showed the typical characteristics of A. viridans, i.e., tetrad arrangements in gram stain, positive pyrrolidonyl aminopeptidase (PYR) and negative leucine aminopeptidase (LAP) reactions, and no growth at 45 degrees C. The isolate was revealed to be highly resistant to penicillin, erythromycin, clindamycin, and ceftriaxone, although most strains of A. viridans isolated from the previously reported patients were susceptible to penicillin and other commonly used antibiotics. Even though A. viridans is rarely associated with human infections, it could be a potential causative agent of bacteremia, especially in immunocompromised patients.
Subject(s)
Agranulocytosis/complications , Bacteremia/complications , Drug Resistance, Multiple, Bacterial , Gram-Positive Bacterial Infections/complications , Penicillins/pharmacology , Streptococcaceae/drug effects , Agranulocytosis/microbiology , Agranulocytosis/physiopathology , Bacteremia/microbiology , Bacteremia/physiopathology , Ceftriaxone/pharmacology , Clindamycin/pharmacology , Erythromycin/pharmacology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/physiopathology , Humans , Male , Middle Aged , Streptococcaceae/isolation & purificationABSTRACT
The novel antipsychotic olanzapine has structural and pharmacological properties similar to clozapine. Until recently, no haematological toxicity has been reported with olanzapine use and it was expected to be a safer alternative. The authors report a case of agranulocytosis induced by olanzapine and reviewed the 11 cases reported in the literature.