Pseudohypobicarbonatemia Caused by an Endogenous Assay Interferent: A New Entity

Serum total carbon dioxide, measured using a chemistry analyzer, and gas panel-derived plasma bicarbonate, calculated from the pH and partial pressure of carbon dioxide, often are used interchangeably for clinical purposes. When they disagree, there is a tendency to accept total carbon dioxide and discredit gas panel-derived plasma bicarbonate values. We report a patient who, during a 5-month hospitalization, had persistently low total carbon dioxide levels (12.4 ± 2.7 [standard deviation] mEq/L [12.4 ± 2.7 mmol/L]), measured using an enzymatic/photometric assay, and a high anion gap (19.2 ± 3.1 mEq/L [19.2 ± 3.1 mmol/L]), suggesting high-anion-gap metabolic acidosis, but who had gas panel-derived plasma bicarbonate (24.0 ± 0.9 mEq/L [24.0 ± 0.9 mmol/L]) and arterial pH values in the reference range. Organic anion levels in blood and urine were unremarkable. Negative interference with the enzymatic assay by the patient's serum was shown by the findings that total carbon dioxide level was 7.0 ± 0.1 mEq/L (7.0 ± 0.1 mmol/L) higher when measured using the electrode-based method than using the enzymatic method (P < 0.01), and the patient's serum, but not control serum, altered the reaction kinetics of the enzymatic assay by producing turbidity, resulting in an initial increase in absorbance and a falsely low total carbon dioxide value. The turbidity may have resulted from precipitation of 1 of 2 paraproteins in the patient's serum or an endogenous antibody binding with an animal protein included in the assay reagents. In summary, a discrepancy between total carbon dioxide level measured using an enzymatic assay and gas panel-derived plasma bicarbonate level was found to be the result of turbidity caused by an endogenous interferent with the total carbon dioxide assay, a novel artifact. When total carbon dioxide and gas panel-derived plasma bicarbonate values disagree, measurement error in total carbon dioxide level should be considered.