Drug-Induced Agranulocytosis: A Mini Review

2016 ◽  
Vol 2 (1) ◽  
pp. 57-59
Author(s):  
Pavithra D ◽  
Praveen D ◽  
Vijey Aanandhi M
Keyword(s):  
Bone Marrow ◽  
Complete Blood Count ◽  
Genetic Manipulation ◽  
White Blood Cells ◽  
Deep Infection ◽  
Morbidity Rate ◽  
Drug Induced ◽  
Serious Adverse Event ◽  
Mortality And Morbidity ◽  
The Individual

Agranulocytosis is also known to be granulopenia, causing neutropenia in circulating blood streams .The destruction of white blood cells takes place which leads to increase in the infection rate in an individual where immune system of the individual is suppressed. The symptoms includes fever, sore throat, mouth ulcers. These are commonly seen as adverse effects of a particular drug and are prescribed for the common diagnostic test for regular monitoring of complete blood count in an admitted patient. Drug-induced agranulocytosis remains a serious adverse event due to occurrence of severe sepsis with deep infection leading to pneumonia, septicaemia, and septic shock in two/third of the patient. Antibiotics seem to be the major causative weapon for this disorder. Certain drugs mainly anti-thyroid drugs, ticlopidine hydrochloride, spironolactone, clozapine, antileptic drugs (clozapine), non-steroidal anti-inflammatory agents, dipyrone are the potential causes. Bone marrow insufficiency followed by destruction or limited proliferative bone marrow destruction takes place. Chemotherapy is rarely seen as a causative agent for this disorder. Genetic manipulation may also include as one of the reason. Agranulocytosis can be recovered within two weeks but the mortality and morbidity rate during the acute phase seems to be high, appropriate adjuvant treatment with broad-spectrum antibiotics are prerequisites for the management of complicated neutropenia. Drugs that are treated for this are expected to change as a resistant drug to the patient. The pathogenesis of agranulocytosis is not yet known. A comprehensive literature search has been carried out in PubMed, Google Scholar and articles pertaining to drug-induced agranulocytosis were selected for review.

scholarly journals PANCYTOPENIA SECONDARY TO AUTOIMMUNE VITAMIN B12 DEFICIENCY IN GRAVES DISEASE

2020 ◽  
Vol 6 (6) ◽  
pp. e282-e285
Author(s):  
Vilmarie Rodriguez ◽  
Kristen M. Gonzales ◽  
Anoop Mohamed Iqbal ◽  
Natasha Arbelo-Ramos ◽  
Kirk D. Wyatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
White Blood Cells ◽  
Vitamin B12 Deficiency ◽  
Thyroid Stimulating Hormone ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Vitamin B ◽  
Thyroid Function Tests ◽  
Drug Induced

Objective: To describe a case of Graves disease (GD) and coexistent pancytopenia associated with autoimmune vitamin B12 deficiency. While thyrotoxicosis and antithyroid drugs can cause pancytopenia, other autoimmune conditions such as vitamin B12 deficiency can occur, leading to severe anemia and pancytopenia. Methods: A 19-year-old female with GD treated with methimazole presented with thyrotoxicosis and evidence of pancytopenia. Diagnostic studies included a complete blood cell count, peripheral blood smears, thyroid function tests, and a bone marrow biopsy. Results: White blood cells were 2.4 × 109 cells/L (reference range [RR] is 3.4 to 9.6 × 109 cells/L), hemoglobin was 7.9 g/dL (RR is 11.6 to 15.0 g/dL), neutrophil count was 1.2 × 109 cells/L, and platelets were 84 × 109 cells/L (RR is 157 to 371 × 109 cells/L). Thyroid-stimulating hormone was <0.01 mIU/L (RR is 0.50 to 4.30 mIU/L), free thyroxine was 3.7 ng/dL (RR is 1.0 to 1.6 ng/dL), and total triiodothyronine was 221 ng/dL (RR is 91 to 218 ng/dL). Due to suspicion for drug-induced pancytopenia, methimazole was discontinued. Three days later, she was hospitalized for a syncopal episode with a further decline in hemoglobin to 6.7 g/dL, neutrophils to 0.68 × 109 cells/L, and platelets to 69 × 109 cells/L. Bone marrow biopsy findings showing marrow hypercellularity and hypersegmented neutrophils suggested vitamin B12 deficiency. Vitamin B12 was <70 ng/L (RR is 180 to 914 ng/L). Intramuscular vitamin B12 injections were initiated, and pancytopenia resolved within 1 month. Conclusion: Although rarely described in the literature, autoimmune vitamin B12 deficiency can be missed as an underlying etiology for pancytopenia in patients with GD. The clinical picture can be further confounded when these patients are treated with antithyroid drugs known to cause bone marrow suppression.

Approach to the Patient with Benign Hematologic Disorders

2013 ◽  
Author(s):  
J Mark Sloan ◽  
David C Seldin
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Complete Blood Count ◽  
White Blood Cells ◽  
Peripheral Blood Smear ◽  
Coagulation System ◽  
Laboratory Findings ◽  
Hematopoietic Stem ◽  
Normal Ranges

Hematology principally concerns the function and disorders of the formed elements of the blood—red blood cells (RBCs), white blood cells (WBCs), and platelets—as well as those factors governing hemostasis. Hematologists have been a powerful force in basic biomedical and translational research. Their work, propelled partly by the ease of collection of blood and bone marrow for study, has enabled an understanding of many blood disorders at a fundamental molecular level. Techniques developed for the study of hematology are often adopted by other disciplines. This chapter discusses the anatomy of the hematopoietic system, hematopoiesis and the bone marrow, physical examination of the hematology patient, evaluation of the complete blood count (CBC) and peripheral blood smear, and coagulation. Tables delineate CBC parameters with normal ranges; peripheral smear findings, descriptions, and RBC indices and significance; laboratory findings in erythrocytosis; diseases commonly associated with eosinophilia and useful workup; common medications strongly associated with thrombocytopenia; and the 4Ts score for determining pretest probability of heparin-induced thrombocytopenia. Figures depict the three fractions of centrifuged blood, the lymph node, hematopoietic stem cells, bone marrow aspirate and biopsy procedure, architecture of the bone marrow microenvironment, petechiae, WBC types found in the smear of peripheral blood, the direct antiglobulin test, myeloid cells, and the coagulation system. This review contains 10 highly rendered figures, 6 tables, and 40 references.

Platelet Disorders

2017 ◽  
Author(s):  
Michael Perry ◽  
John Bedolla ◽  
Truman John Milling
Keyword(s):  
Bone Marrow ◽  
Platelet Transfusion ◽  
Bleeding Time ◽  
Complete Blood Count ◽  
Systemic Disease ◽  
Coagulation Cascade ◽  
Platelet Dysfunction ◽  
Drug Induced ◽  
Platelet Disorders ◽  
Plug Formation

Hemostasis occurs in two steps: platelet plug formation followed by fibrin deposition. Platelet disorders cause incomplete or absent platelet plug formation. Platelets form in bone marrow and have an 8- to 9-day life span. A careful history and physical examination can distinguish between platelets or the coagulation cascade as the cause of deranged hemostasis. Platelet disorders are characterized by mucosal and small vessel bleeding, and petechiae are characteristic. A complete blood count and prothrombin time/international normalized ratio testing reveal most causes. Many drugs can alter platelet production, function, and longevity, but antiplatelet therapy is the most common cause. Other causes include congenital, medication side effects, sepsis, bone marrow suppression, and systemic disease. The platelet count may be low, elevated, or normal. Bleeding time is virtually always prolonged in platelet dysfunction. Therapy for platelet dysfunction depends on the etiology and severity. Platelets are short-lived, and platelet transfusion may be necessary in the unstable or actively bleeding patient. In most other cases, removing the cause or treating the systemic disease will improve hemostasis. Emergency physicians treating patients with abnormal bleeding should understand the coagulation cascade and drug-induced coagulopathy from older and newer agents. Key words: bleeding time, coagulopathy, drug induced, hemostasis, megakaryocyte, mucosal bleeding, petechiae, platelet plug, platelet transfusion, platelets, thrombocytopenia

Nitrofurantoin-induced agranulocytosis

2021 ◽  
Vol 14 (11) ◽  
pp. e246788
Author(s):  
Vanessa Lopes ◽  
Joana Ramos ◽  
Patrícia Dias ◽  
Arsénio Santos
Keyword(s):  
Bone Marrow ◽  
Adverse Reaction ◽  
Blood Count ◽  
Adverse Reactions ◽  
Bone Marrow Aspirate ◽  
Complete Blood Count ◽  
Complete Recovery ◽  
Drug Induced ◽  
Life Threatening ◽  
Severe Adverse Reactions

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.

Addiction and Liver Disease

2014 ◽  
Vol 25 (2) ◽  
pp. 75-83
Author(s):  
Md Akmat Ali ◽  
Farida Yeasmin ◽  
MN Nag
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Drug Users ◽  
Harmful Effect ◽  
Main Role ◽  
Drug Induced ◽  
Mortality And Morbidity ◽  
Other Substances ◽  
Excessive Alcohol ◽  
Medicine Today

Drug induced liver disease is a global problem. The aims of the study are to know the recreational drugs causing harmful effect on liver, epidemiology of addiction; pathophysiology and their consequences. The major findings published to date concerning different agents causing addiction and liver disease, their implications with regard to understanding disease mechanisms and their amplitude or spectrum are described. Addiction not only invites lot of sufferings to the family and the country, but also responsible for different types of liver disease including fatty liver, hepatitis and liver failure; responsible for mortality and morbidity. Among the addiction causing substances alcohol playing the main role for liver disease worldwide. Indirect effects of addiction on liver are hepatitis B, hepatitis C and their complication, mainly due to contamination of sharing needle. Majority of people in Bangladesh are life long abstainer. Excessive alcohol beverages and other substances like heroin, amphetamine are not harmless, rather they can cause serious liver diseases. There are some differences in prevalence of addiction and liver diseases among countries. Intravenous drug users are affected both directly and indirectly due to contaminated needle sharing . DOI: http://dx.doi.org/10.3329/medtoday.v25i2.17926 Medicine Today 2013 Vol.25(2): 75-83

Bone Marrow Culture Yield for the Diagnosis of Opportunistic Diseases in Patients with AIDS and Disseminated Kaposi Sarcoma

2020 ◽  
Vol 18 (4) ◽  
pp. 277-282
Author(s):  
P. Cornejo-Juárez ◽  
B. Islas-Muñoz ◽  
A.F. Ramírez-Ibargüen ◽  
G. Rosales-Pedraza ◽  
B. Chávez-Mazari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Blood Count ◽  
Kaposi Sarcoma ◽  
Opportunistic Pathogens ◽  
Reactive Protein ◽  
Negative Results ◽  
Recent Diagnosis ◽  
Male Patients ◽  
Liver Tests ◽  
Rule Out

Background: Disseminated Kaposi sarcoma (DKS) is present in patients with advanced HIV infection in whom co-infection with other opportunistic pathogens can occur. Bone marrow (BM) aspirate and biopsy comprises a robust diagnostic tool in patients with fever, cytopenias, and abnormal liver tests. However, the yield in patients with DKS has not been determined. Objective: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS. Methods: We included 40 male patients with recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections. Results: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In another four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found on comparing complete blood-count abnormalities. Conclusion: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

scholarly journals Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age

2021 ◽  
pp. 026988112110034
Author(s):  
Leif Hommers ◽  
Maike Scherf-Clavel ◽  
Roberta Stempel ◽  
Julian Roth ◽  
Matthias Falter ◽  
...  
Keyword(s):  
Qt Interval ◽  
Multivariate Regression Analysis ◽  
Cardiac Repolarization ◽  
Qtc Interval ◽  
Serum Concentrations ◽  
Drug Induced ◽  
Individual Level ◽  
Main Determinants ◽  
The Individual ◽  
Polygenic Variation

Background: Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified. Aims: To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval. Methods: Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al. Results: Linear regression modelling showed a significant association of the individual polygenic QT interval score (ßstd = 0.176, p < 0.001) and age (ßstd = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia’s formula. Sex showed a nominal trend towards significance (ßstd = 0.064, p = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( n = 588) showed a significant association of potassium serum concentrations with the QTc interval (ßstd = −0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( n = 26, ßstd = 0.101, p = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association. Conclusions: Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.

scholarly journals GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natsuko Ohashi ◽  
Tomoya Terashima ◽  
Miwako Katagi ◽  
Yuki Nakae ◽  
Junko Okano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Bone Marrow ◽  
Mouse Model ◽  
Lentiviral Vector ◽  
White Blood Cells ◽  
Glutamate Toxicity ◽  
Pathological Lesion ◽  
Arginase 1 ◽  
Therapy Strategy

AbstractAmyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12–14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4–7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.

scholarly journals Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

2020 ◽  
Vol 21 (24) ◽  
pp. 9759
Author(s):  
Agnieszka Arthur ◽  
Stan Gronthos
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Genetic Manipulation ◽  
Bioactive Molecules ◽  
Long Bone ◽  
Differentiation Potential ◽  
Skeletal Tissue ◽  
Recent Developments ◽  
Multipotent Differentiation ◽  
Craniofacial Defects

There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.

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