Case reportFalsely increased chloride and missed anion gap elevation during treatment with sodium thiosulfate
Introduction
Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare disease characterized by painful cutaneous ulcers formed secondary to dystrophic calcium deposition in the vasculature of the skin. The disease occurs most often in patients with end-stage renal disease on hemodialysis or those with chronic inflammatory conditions even without renal failure [1]. Although the disease has historically portended a poor prognosis, patients have been successfully treated in the last decade with sodium thiosulfate (STS), a drug previously used to treat cyanide poisoning [1], [2].
While the drug commonly causes mild gastrointestinal symptoms, the most serious side effect is that of severe anion gap acidosis. To monitor patients for this effect, plasma electrolytes are measured after each dose [3], [4]. We recently encountered an unexplained increase of the plasma chloride concentration in a patient receiving STS, and sought an explanation for this finding.
Section snippets
Case report
A 33-y-old woman with systemic lupus erythematosus and associated vasculitis and nephritis presented to the clinic for continuing treatment of bilateral lower extremity ulcers. The ulcers had been present for 18 months, and had a biopsy-proven diagnosis of calciphylaxis. Despite treatment of her lupus with immunosuppression, the wounds continued to worsen. Eight months before the current clinic visit she was started on 25-g intravenous infusions of sodium thiosulfate (STS) thrice weekly to treat
Methods
To examine the effect of STS on chloride measurements by clinical analyzers, we prepared samples of pooled plasma with 12 concentrations of STS. The concentration of chloride in each of these samples was measured by 9 different analyzers. The maximum concentration of STS was chosen to represent the highest concentration likely to be seen in plasma after infusion of a 12.5-g dose of STS. Assuming that the 12.5-g dose of STS pentahydrate is distributed in a typical blood volume of 5 l with a
Results
The dose–response curve illustrating the relationship of STS concentration and the chloride results from the various analyzers is shown in Fig. 1. Using SAS software (SAS Institute INC) an analysis of covariance was performed on the data and showed significant non-homogeneity (P < 0.0001) of the slopes of the thiosulfate dose–response curves among the analyzers. Regression analysis of these dose–response curves resulted in slopes that were statistically significantly different from zero for all
Discussion
These studies demonstrate that STS produces a positive interference in chloride measurements on most of the representative analytical platforms studied. The levels of interference can be grouped into 3 categories based on expected clinical significance: (i) analyzers that showed large interference beyond the CLIA acceptable limit of 5% variation (Architect 16200, iSTAT1, StatProfile pHOx Plus, and Radiometer ABL735); (ii) those that showed statistically significant interference without
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Cited by (7)
Data on the clinical, analytical, and laboratory factors associated with negative anion gaps at an academic medical center
2022, Data in BriefCitation Excerpt :Certain pathologic states, drugs, and laboratory abnormalities have been associated with low anion gap measurements [1,6,8,13]. These include hypoalbuminemia [8,14-16], chronic respiratory acidosis with compensatory metabolic alkalosis [17], hypercalcemia [18], hypermagnesemia [19], marked hyperkalemia [9], polyclonal gammopathy [20], presence of paraproteins (e.g., multiple myeloma) [21,22], pseudohyponatremia (due to factors such as hypertriglyceridemia, severe hypercholesterolemia, or hyperproteinemia) [23], pseudohyperbicarbonemia (such as due to ketoacidosis or monoclonal proteins) [9], bromism (intoxication with bromides) [24], iodine administration [10], lithium toxicity [19,25], thiosulfate [26], salicylate poisoning [9,12], and administration of the antimicrobial polymyxin B [27]. Previous studies have also identified pre-analytical specimen issues (e.g., contaminated specimens), analytical errors, and post-analytical errors (e.g., data entry mistake into the medical record) as a relatively frequent cause of low anion gaps [1,6,28].
Approach to the Patient with a Negative Anion Gap
2016, American Journal of Kidney DiseasesCitation Excerpt :Of note, a similar artifact was recently reported in patients receiving sodium thiosulfate, which has been used to treat calciphylaxis and cyanide poisoning.56 As with salicylism, the artifact is due to the effect of thiosulfate on the electrode and is very electrode specific.57 Box 1 lists causes of low and negative anion gaps and categorizes them by mechanism.
Falsely elevated chloride during treatment with sodium thiosulfate
2014, Clinica Chimica ActaThiosulfate
2017, Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned PatientA fatal case of calciphylaxis in a patient with systemic lupus erythematosus and normal renal function
2016, Journal of Rheumatology