Falsely increased chloride and missed anion gap elevation during treatment with sodium thiosulfate

Sodium thiosulfate (STS) is used to treat calciphylaxis and cyanide poisoning, but can lead to a serious anion-gap acidosis. We suspected that the calculated anion gap in a patient treated with STS for calciphylaxis was decreased to normal by a falsely increased chloride, and we hypothesized that STS directly interfered with chloride measurements.

Plasma pools were prepared with 12 concentrations of STS from 0 to 20 mmol/l. Chloride was measured in each sample on 9 analyzers: Architect 16200, StatProfile pHOx Plus, RapidLab 1265®, Vitros 350®, Advia 1800, Roche Modular, iSTAT1, RAPIDpoint 500, and Radiometer ABL735.

Statistically significant, dose-dependent increases in reported chloride concentrations were seen with all analyzers except the RAPIDpoint 500 and Vitros. The increases ranged from 5 to 75 mmol/l at the peak thiosulfate concentrations (33 mmol/l) expected in treated patients. The CLIA-allowable error of 5% was exceeded by 4 analyzers (Architect 16200, iSTAT1, StatProfile pHOx Plus, and Radiometer ABL735). The RAPIDpoint 500 showed a 3-mmol/l decrease in measured chloride over the tested range. The Vitros analyzer showed no interference.

Interference of STS in chloride measurement in several common analyzers may lead to erroneous anion-gap calculations and confound the diagnosis of STS-induced anion-gap acidosis.