Assay-Dependent Effects of EDTA Contamination on Magnesium and Iron

Inadvertent submission of ethylenediaminetetraacetic acid (EDTA) based plasma in place of heparinized plasma or contamination of serum or heparinized plasma with EDTA can alter select laboratory measurements. While indications such as factitious hyperkalemia (if introduced via K₂EDTA or K₃EDTA), hypocalcaemia and abnormally low alkaline phosphatase (ALP) are recognized indicators of EDTA contamination, the impact of EDTA on Mg²⁺ and Fe²⁺ measurements remains uncertain and conflicting.

Herein, we derived the EDTA concentration required to cause a 50 % decline (EC50_[EDTA]) for Ca²⁺, ALP, Mg²⁺, and Fe²⁺ across two methodologies (on Roche cobas c 303 and Abbott Alinity c) in the presence of EDTA concentration across plasma and serum pools. The concentration of EDTA required to exceed the allowable performance limit (APL_[EDTA]) was also derived across methods.

Mg²⁺ measured by an isocitrate dehydrogenase method was resilient against EDTA, while Mg²⁺ measured by xylidyl blue had an EC50_[EDTA] and APL_[EDTA] of 0.78-1.18 mmol/L and 0.16-0.34 mmol/L, respectively. Fe²⁺ measured with a ferene method was resilient to EDTA, whereas the ferrrozine method indicated EC50_[EDTA] and APL_[EDTA] of 5.6-8.86 mmol/L and 4.68-5.46 mmol/L, respectively. Ca²⁺ and ALP exhibited larger EC50_[EDTA] on the Abbott Alinity c.

Hypomagnesemia and hypoferremia are not definitive markers of potential EDTA contamination, as Mg²⁺ and Fe²⁺ measurements show method-dependent susceptibilities.