Interfering Substance in Chemistry Results
A 60-year-old man with a history of alcohol use disorder is admitted with confusion and jaundice. Laboratory results show: sodium 128 mmol/L, potassium 3.2 mmol/L, chloride 98 mmol/L, bicarbonate 18 mmol/L, glucose 85 mg/dL, BUN 10 mg/dL, creatinine 0.6 mg/dL, total protein 5.0 g/dL, albumin 2.5 g/dL, total bilirubin 4.0 mg/dL, direct bilirubin 2.0 mg/dL, AST 120 U/L, ALT 80 U/L, ALP 150 U/L, GGT 200 U/L. The calculated anion gap is 12 mmol/L. The plasma sample is visibly hemolyzed (3+). The lab uses a spectrophotometric method for creatinine (Jaffe) and an enzymatic method for ammonia (not ordered). The clinician suspects alcoholic hepatitis and asks for a serum osmolality and an osmolal gap. The measured serum osmolality is 320 mOsm/kg. The calculated osmolality (2Na + glucose/18 + BUN/2.8) is 280 mOsm/kg.
1. Calculate the osmolal gap and interpret the results in the context of the clinical picture and the hemolyzed sample.
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The osmolal gap is measured osmolality minus calculated osmolality: 320 - 280 = 40 mOsm/kg. An osmolal gap >10 mOsm/kg suggests the presence of unmeasured osmoles, such as ethanol, methanol, ethylene glycol, isopropanol, or mannitol. Given the history of alcohol use disorder, ethanol or another alcohol is likely. However, the sample is hemolyzed, which can falsely elevate measured osmolality due to release of intracellular contents, but hemolysis typically increases osmolality by only a few mOsm/kg. A gap of 40 is significant and unlikely due to hemolysis alone. The patient's anion gap is 12 (normal 8-12), which does not show a high anion gap metabolic acidosis typical of methanol or ethylene glycol poisoning. Ethanol would not cause a high anion gap but would increase osmolality. The patient's confusion and jaundice could be due to alcoholic hepatitis, but the osmolal gap suggests recent ethanol ingestion. The lab should be aware that hemolysis can interfere with some methods; however, the osmolality is measured by freezing point depression, which is not affected by hemolysis. The calculated osmolality uses sodium, glucose, and BUN, which may be affected by hemolysis if the sodium is falsely low due to pseudohyponatremia (not likely with normal protein). The results should be interpreted with caution, and the clinician should be informed of the osmolal gap and the possibility of ethanol or other alcohol. Further testing for specific alcohols (ethanol, methanol, ethylene glycol) should be recommended.
2. How might the hemolyzed sample affect the other chemistry results, and what steps should the laboratory take?
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Hemolysis can falsely increase potassium, AST, ALT, LDH, and phosphate due to release from red cells. In this case, potassium is 3.2 mmol/L, which is not elevated; hemolysis would tend to increase potassium, so the true potassium may be even lower. AST and ALT are elevated, but hemolysis can contribute; however, the AST/ALT ratio >1 is consistent with alcoholic hepatitis. Bilirubin and ALP are less affected. The Jaffe creatinine method can be affected by hemolysis, but the creatinine is low, so not a concern. The laboratory should: (1) Note the hemolysis on the report and consider recollecting if clinically indicated. (2) For potassium, if the result is critical or inconsistent, request a new sample. (3) For AST/ALT, interpret with caution; hemolysis may falsely elevate. (4) Communicate with the clinician about the hemolysis and its potential effects. (5) If the sample is unsuitable, request a redraw. (6) For osmolality, the freezing point method is not affected by hemolysis, so the result is valid. (7) The lab should also check for lipemia or icterus, which can interfere with some assays. The bilirubin is elevated (icterus) and can interfere with creatinine and other assays; the lab should use appropriate corrections or methods.