Sample flags, low anion gap—solving lab puzzles​on October 31, 2025 at 4:00 am

“There are labs using the wrong anion gap,” Dr. El-Khoury said. “There are two distributions based on different methods, one that’s much lower and one that’s higher.” And clinicians will call the laboratory to ask why an anion gap reference interval is too low or high, unaware that what they see in textbooks and online is based on other methods. “People say, ‘If it’s over 12, we should be flagging.’ No, your method is up to 17. Depending on your method,” he said, “you could have these slight shifts in electrolytes that contribute to bigger shifts in the anion gap.”

The takeaways: “Problems with reference intervals can surface as a perception of low or high results among your clinicians,” he said. And IVD manufacturers do not provide reference intervals for calculated measures. “So it’s something you have to take care of” by consulting the literature to determine reference intervals for equations and calculations derived using similar methods for the individual tests.

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