False positives in plasma ammonia measurement and their clinical impact in a pediatric population

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Abstract

Objective:

Plasma ammonia measurement is greatly influenced by pre-analytical conditions, which may lead to false positives. We wanted to evaluate the prevalence and clinical impact of plasma ammonia false positives in a pediatric population.

Design and methods:

Over a 28-month period, charts of patients with elevated ammonemia were retrospectively reviewed to identify false positives defined as elevated concentrations that subsequently normalized without plausible explanation for the elevations.

Results:

1880 Ammonia measurements were available in 479 patients. Elevated results that subsequently normalized were found in 86 patients. Forty-one (48%) of these patients had most likely falsely elevated ammonemia. Additional blood sampling and laboratory testing were the most frequent consequences of false positives.

Conclusion:

There is a high proportion of false positives among elevated plasma ammonia measurements. Capillary samples and delay between sampling and centrifugation are possible contributing factors. Clinical consequences of false positives were most often limited.

Introduction

Plasma ammonia concentrations are kept within a narrow range in healthy individuals. In excess, ammonia is a potent neurotoxin [1], [2]. Hyperammonemia can be associated with lethargy, confusion, vomiting, coma and brain edema that could lead to death. The aetiologies of hyperammonemia are diverse and can be due to inherited disorders of metabolism such as urea cycle defects and organic acidurias, or secondary to hepatic dysfunction, shock or other diseases. Distinction between these disorders needs further laboratory evaluation including plasma amino acid chromatography, urinary organic acid chromatography and urinary orotic acid determination [3].

Plasma ammonia measurement is greatly influenced by pre-analytical conditions, which may lead to false positives. In particular, ammonia concentration increases spontaneously in blood and plasma after collection. This increase is produced mainly by the release of ammonia from erythrocytes and deamination of plasma amino acids [4], [5]. Plasma ammonia concentration is also affected by the venipuncture technique and the temperature of the sample. Ammonia is stable for less than 15 min at 4 °C [6]. Considering the importance of this biochemical marker and the potential impact of false positives on patient's investigation and treatment, care should be taken to minimize artifacts caused by pre-analytical conditions. A consensus statement from the Urea Cycle Disorders Conference Group [7] suggested that blood should be collected in a pre-chilled, ammonia-free tube, kept on ice and delivered immediately to the laboratory. Plasma should be separated within 15 min of collection. If the assay is not run immediately plasma should be stored frozen at − 70 °C. In addition, capillary blood should not be used because this incurs a greater risk of hemolysis and tissue damages that could result in falsely elevated ammonia [8], [9], [10]. However, these ideal conditions cannot always be met in a clinical setting.

Although measurement of ammonia concentration in blood is fraught with difficulty, data on the prevalence of spuriously elevated results in different clinical settings are extremely limited and anecdotal [5], [11], [12]. Therefore, the objectives of our study were: (a) to determine the proportion of false positives for ammonia measurement in a pediatric population; (b) to establish the clinical consequences of these false positives; and (c) to examine pre-analytical conditions that could lead to these false positives.

Section snippets

Study design and data sources

Results of all ammonia measurements done between March 2001 and July 2003 were retrieved from the database of the clinical biochemistry laboratory of Ste-Justine Hospital, Montreal, Quebec, Canada. Ste-Justine Hospital is a tertiary care pediatric hospital and a reference center for patients with inborn errors of metabolism. We defined false positive as any elevated result that subsequently returned to normal without plausible explanation for its elevation and ensuing normalization. Sixty-three

Study population

A total of 1880 ammonia results were available for the study. Sixty-nine percent of ammonia determinations were done in hospitalized patients and 80% for children older than 1 month of age (Table 1). Ammonia concentrations ranged from 5 to 1863 μmol/L, with a median of 65 μmol/L in infants less than 1 month of age and 50 μmol/L in those older than 1 month of age (p < 0.001 for comparison between age groups). Median ammonia concentration was significantly higher in hospitalized compared to

Discussion

Our study is the first attempt to estimate the proportion of false positives among children and adolescents with elevated plasma ammonia as well as the consequences of these falsely elevated results.

References (15)

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    Citation Excerpt :

    Hyperammonaemia is a medical emergency, as elevated levels of free ammonia are neurotoxic, leading to cerebral oedema, coma and potentially death [1–5]. Hyperammonaemia is a significant complication of several metabolic disorders (not necessarily confined to children) including Urea Cycle Disorders, Organic Acidaemias, and Fatty Acid Oxidation defects [1–4]. Hyperammonaemia may be present in various acquired conditions for example, acute or chronic liver failure, Valproic acid treatment and L-Asparaginase therapy [1–5].

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