scholarly journals Quantifying Drug‐Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model

2019 ◽  
Vol 8 (11) ◽  
pp. 858-868 ◽  
Author(s):  
Chiara Fornari ◽  
Lenka Oplustil O'Connor ◽  
Carmen Pin ◽  
Aaron Smith ◽  
James W.T. Yates ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Toxicity ◽  
Systems Pharmacology ◽  
Drug Induced ◽  
Systems Pharmacology Model

Piperacillin Induced Thrombocytopenia in Critical Care Patients as Compared to Non Critical Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3916-3916
Author(s):  
Seema Naik ◽  
Ashish Sangal ◽  
Srinivas Kodali ◽  
Theresa Dumlao ◽  
Madhumati Kalavar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antimicrobial Agents ◽  
Retrospective Chart Review ◽  
Histamine Receptor ◽  
Bone Marrow Toxicity ◽  
Bacterial Strains ◽  
Drug Induced ◽  
Platelet Recovery ◽  
Factors Associated ◽  
Icu Stay

Abstract Introduction: Drug-induced thrombocytopenia in the critically ill is documented in the literature with limited frequency. Implicated agents are antiepileptics, anticoagulants, antiarrhythmics, histamine receptor antagonists, and antimicrobials .Piperacillin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. Methods: We conducted a retrospective chart review of patients admitted during a 6-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with the use of piperacillin ICU versus non ICU patients. Results: Data were collected for 154 patients (M:71, F:83),), admitted to the ICU and Non-ICU setting. 55% of the patients were more than 65 years of age. Platelet drop occurred in 123 patients. Thrombocytopenic patients had a longer ICU stay (11.2 vs 5.6 days) and greater mortality (9% vs 3%) than nonthrombocytopenic patients .The patients developed thrombocytopenia as follows:Mild(100–150k): 22 pts-(15%) ; Moderate(50–100k): 7 pts-(5%) ;and Severe(<50k): 4 pts- (3%). The other drugs during hospitalization were heparin (30%), ceftazidime(11%), famotidine(9%), bactrim(0.3%),esomeprazole (11%), aspirin(18%). Patients received piperacillin for mean duration of 9 days. In patients with thrombocytopenia, the platelet levels dropped by a mean of 15.15% on Day 2 from pretreatment values (range, 2% to 61%) while they were receiving piperacillin. On average, the nadir platelet count was reached 7 days after treatment with piperacillin was initiated (range, 2 to14days). The median time required for platelet recovery was 8.4 days (range 5.6 in ICU to 11.2 in Non-ICU pts).Bleeding was unusual in patients with thrombocytopenia. Platelet transfusions failed to elevate platelet counts. Discussion: Thrombocytopenia occurs in 23–63% of patients in the intensive care unit (ICU). Factors associated with the disorder in these patients include sepsis, disseminated intravascular coagulation (DIC), blood transfusions, central catheters, and drugs, some of which may have a significant effect on morbidity and mortality. The major mechanisms of drug-induced thrombocytopenia are immune-mediated platelet destruction and concentration-dependent bone marrow suppression. Bone marrow toxicity, mainly neutropenia, has been described as an uncommon secondary effect of most beta-lactams, and it is usually related to large cumulative doses. Conclusion: Thrombocytopenia is associated with an increased ICU stay and increased mortality. Thrombocytopenic events associated with antimicrobial agents in the ICU may warrant further investigation because of the increased administration of these drugs to combat more virulent bacterial strains.

Hemolytic Anemia and Pancytopenia Induced by Cefoxitin

1983 ◽  
Vol 17 (11) ◽  
pp. 816-818 ◽  
Author(s):  
Olga H. DeTorres
Keyword(s):  
Bone Marrow ◽  
Hemolytic Anemia ◽  
Total Bilirubin ◽  
Lower Lobe ◽  
Bone Marrow Aspiration ◽  
The Other ◽  
Bone Marrow Toxicity ◽  
Drug Induced ◽  
Cell Series ◽  
Blood Elements

A 77-year-old man received cefoxitin for the treatment of peritonitis. He developed hemolytic anemia and became clinically jaundiced. The patient was switched from cefoxitin to doxycycline. His total bilirubin decreased and his hematocrit increased. Several weeks later he developed septicemia. For an infiltration in the left lower lobe, he was treated with cefoxitin and gentamicin. The patient proceeded to develop a mild granulocytopenia and thrombocytopenia. Anemia was not seen because the patient was transfused several times. Bone marrow aspiration showed a mildly hypocellular marrow with a depression of all cell series, suggesting drug-induced bone marrow toxicity. Nine days after discontinuing cefoxitin, his blood elements had gone back to normal. This is the fourth case on file at Merck Sharp & Dohme of hemolytic anemia induced by cefoxitin. There have been several reports of hemolytic anemia or pancytopenia caused by cephalothin, but few, if any, citing the other cephalosporins, particularly cefoxitin. Clinicians should be made aware of the possibility of hematologic toxicities occurring with cefoxitin therapy. Patients should have their erythrocytes, leukocytes, and platelets monitored while on this drug.

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.

Bone marrow toxicity induced by oral benzo[a]pyrene: Protection resides at the level of the intestine and liver

1983 ◽  
Vol 70 (3) ◽  
pp. 390-401 ◽  
Author(s):  
Catherine Legraverend ◽  
David E. Harrison ◽  
Francis W. Ruscetti ◽  
Daniel W. Nebert
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Toxicity

Spironolactone-Induced Agranulocytosis

1997 ◽  
Vol 31 (5) ◽  
pp. 582-585 ◽  
Author(s):  
Anna M Whitling ◽  
Pablo E Pérgola ◽  
John Lee Sang ◽  
Robert L Talbert
Keyword(s):  
Risk Factors ◽  
Adverse Effect ◽  
Bone Marrow ◽  
Leukocyte Count ◽  
Laboratory Data ◽  
University Hospital ◽  
Drug Induced ◽  
Bone Marrow Biopsies ◽  
Case Summary ◽  
Before And After

OBJECTIVE: TO report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 × 103/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 × 103/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drag dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.

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