Improved assay protocol for measurement of ammonia on the Roche Cobas 8000 automated platform

Kaplon, J.; Groot, J.J. de; Straalen, Jan P. van; Heckman, Michael G.; Fischer, Jochen

doi:10.1016/j.plabm.2018.e00115

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…This would typically require additional studies by the laboratory to better define impact of icterus on specific assays. A third approach is to use specimen dilution to limit icteric interference, as has been described for Roche Diagnostics creatinine [ 35 ] and ammonia assays [ 36 ]. And finally, laboratories can perform the effort to validate their own thresholds for icterus.…”

Section: Discussionmentioning

confidence: 99%

Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus

Mainali

Merrill

Krasowski

2021

Practical Laboratory Medicine

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Objectives The aims of this study were to identify the causes of severe icterus in an academic medical center patient population and to assess the impact of icterus on clinical chemistry testing using assay package insert thresholds. Design and Methods : In this retrospective study at an academic medical center core clinical laboratory, icteric, hemolysis, and lipemia indices were available for all serum and plasma chemistry specimens analyzed on Roche Diagnostics cobas 8000 analyzers over a 12-month period, encompassing 414,502 specimens from 94,081 unique patients (51,851 females; 42,230 males) including children, inpatient, outpatient, and emergency department patients. Extensive chart review was done for all 57 patients (4 pediatric, 53 adult; 534 total specimens) who had one or more samples with an icteric index of 40 or higher (defined as severe icterus). Results Specimen icteric index exceeded package insert icteric index thresholds in 0.14% of clinical chemistry assays, with the highest number of instances for creatinine (1358 samples, 0.6% of total tests), total protein (1194 samples, 2.2%), and ammonia (161 samples, 3.9%). The 57 patients with an icteric index of 40 or higher accounted for 49.7% of all instances where the icteric index exceeded the specific assay package insert limit. The most common etiologies of this group of 57 patients were alcohol-related liver disease (34 patients), biliary tract disease (7 patients), and neoplasms (6 patients). Conclusions Approximately half of all instances where specimen icteric index exceeded assay package insert thresholds occurred in a small cohort of patients with severe liver/biliary tract disease.

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Section: Discussionmentioning

confidence: 99%

Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus

Mainali

Merrill

Krasowski

2021

Practical Laboratory Medicine

View full text Add to dashboard Cite

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“…Furthermore, the patient was fasted for at least 12 h prior to any of the blood ammonia concentrations reported in this paper. It is known that lipemia interferes with blood ammonia concentration measurement ( 27 ). It is recommended that blood samples are collected at least 5–6 h after the administration of Intralipid, to prevent lipemia interfering with test results ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Resolution of Severe Neurologic Signs Following Intravenous Lipid Emulsion Therapy in a Young Dog With a Portosystemic Shunt: Case Report

2021

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A 5-month-old male intact Great Pyrenees was presented for an acute onset of severe neurologic signs (stupor, absent menace, intermittent head turn to the left). The patient's history included possible naproxen ingestion with a maximum ingested dose of 59 mg/kg, exceeding the reported dose of >50 mg/kg known to cause neurologic signs. Blood sampling for baseline bloodwork was performed, and intravenous lipid emulsion (ILE) was subsequently administered, for treatment of the suspected toxicosis. Due to severe and life-threatening neurologic signs, other methods of decontamination were contraindicated and unlikely to be effective; extracorporeal therapy was also unavailable. Complete resolution of neurologic signs occurred 30 min after completion of ILE therapy. At this time, the owners found the missing naproxen tablets after returning home and the bloodwork results returned revealing findings consistent with hepatic encephalopathy. The fasted blood ammonia concentration immediately prior to ILE administration was 702.1 μg/dL (reference interval, RI: 24–36 μg/dL) and decreased to 194.1 μg/dL 24 h later. In the first 24 h, the patient also received three doses of lactulose, N-acetylcysteine, and intravenous fluids. The patient was subsequently diagnosed with a single, large intrahepatic portosystemic shunt via computed tomography and underwent an endovascular coil embolization procedure. Given the rapid and dramatic improvement in severe neurologic signs after ILE therapy alone, it is strongly suspected that this treatment resulted in improvement of hepatic encephalopathy.

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Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

Gallego‐Durán

Ampuero

Pastor-Ramírez

et al. 2022

Sci Rep

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The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr −/−). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m2), diabetes mellitus and ALT were found to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.

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Improved assay protocol for measurement of ammonia on the Roche Cobas 8000 automated platform

Cited by 3 publications

References 8 publications

Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus

Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus

Resolution of Severe Neurologic Signs Following Intravenous Lipid Emulsion Therapy in a Young Dog With a Portosystemic Shunt: Case Report

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

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