A physician requested that electrolytes on a multiple myeloma patient specimen be run by direct ISE and not indirect ISE because:

• A. Excess protein binds Na in indirect ISE
• B. Na falsely increased by indirect ISE
• C. Na falsely decreased by indirect ISE
• D. Excess protein reacts with diluent in indirect ISE

Answer: (C)

Elevated serum protein in conditions like multiple myeloma changes the plasma composition by reducing the fraction of plasma water. Indirect ISE dilutes the sample and assumes a constant water fraction, so when the water content is actually lower, the diluted measurement yields a sodium value that is spuriously low. This is known as pseudohyponatremia. Direct ISE measures ion activity in undiluted plasma, reflecting the true sodium in the plasma water without being affected by changes in protein concentration. So using direct ISE avoids this artifact and gives a more accurate sodium result in hyperproteinemic states.