Zinc heparin introduces a preanalytical error in the measurement of ionized calcium concentration

In this study we determined how zinc heparin affected ionized calcium concentration determinations. Zinc heparin produced a positive bias (0.020-0.067 mmol l-1) in ionized calcium measurement in serum/whole blood and a negative bias (-0.035 to -0.110 mmol l-1) with aqueous ionized calcium standards. To test if the positive bias was due to zinc ions displacing calcium from its protein-calcium complexes, we reproduced the effect by adding ZnCl2 to pooled serum. Changes in [ZnCl2] (0.1-0.5 mmol l-1) caused a dose-dependent increase, a constant bias ([ZnCl2], 0.5-1.25 mmol l-1) or a dose-dependent decrease ([ZnCl2] > 1.25 mmol l-1) in ionized calcium concentration, independent of pH. Similar results were obtained when zinc concentration of the specimen was changed by varying the volume of blood collected into syringes containing zinc heparin. We conclude that zinc heparin produces a positive bias in ionized calcium measurement in protein-based matrices.