Total Serum Calcium Spike-Recovery Experiments to Investigate Bones of Contention in Clinical Laboratories

Background To help assess patient safety risks associated with ongoing differences in total calcium assays following bias shifts, we performed spike-recovery experiments within our clinical chemistry external quality assessment (EQA) schemes to evaluate bias and recovery against a reference measurement procedure (RMP). Methods Aqueous calcium chloride dihydrate was spiked (0.30/0.60 mmol/L; 1.20/2.40 mg/dL) into pooled human serum. Bias was assessed against RMP-assigned targets and recovery against added spikes. Minimum analytical performance specifications (APS) for standard measurement uncertainty (1.36%) defined acceptable bias/recovery. Results Commercially available analytical principles across analytical platforms did not achieve adequate bias against RMP-assigned targets and recovery against added spikes for total calcium in 3 EQA specimens. Roche Cobas (5-nitro-5′-methyl-1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid [NM-BAPTA]), Roche Cobas Pro (NM-BAPTA), and Beckman AU (Arsenazo III) methods exhibited better bias and long-term stability. The Abbott Alinity (Arsenazo III) method exhibited notable negative bias (−2.33% to −3.10%), apparently coinciding with the introduction of Abbott Calcium2. Negative bias was present to a lesser extent in the Abbott Architect (Arsenazo III). The Siemens Atellica (cresolphthalein complexone) assay exhibited notable proportional over recovery (110.2% to 112.0%). There was some positive bias in the Siemens Atellica (Arsenazo III) and QuidelOrtho (dry slide/sensor) methods. Conclusions Differences across analytical principles/platforms and difficulties achieving minimum APS for total calcium were shown within our EQA schemes, notably negative bias for Abbott Alinity and Architect (Arsenazo III), over-recovery for Siemens Atellica (cresolphthalein complexone) and positive bias for Siemens Atellica (Arsenazo III). Understanding the impact on clinical decision-making and patient outcomes is imperative for managing any patient safety risks.