During a talk at the 2015 American Association for Clinical Chemistry meeting, Dina Greene, Ph.D., associate director of chemistry at the University of Washington Medical Center, highlighted a complicated case that she investigated along with Nikola Baumann, Ph.D., co-director of the central clinical laboratory and director of central processing
at the Mayo Clinic in Rochester, Minnesota. The case, published in CAP TODAY, helps illustrate the complex challenge of aligning laboratory results across a health care network.
A 29-year-old woman who was nine weeks pregnant presented to one of Kaiser’s Northern California hospitals with severe nausea and vomiting. Nearly all of her laboratory values were unremarkable, except for an elevation of her aspartate aminotransferase, at 105 U/L. The reference range for that hospital laboratory was 14–36 U/L, using an Ortho Clinical Diagnostics Vitros analyzer.
According to the article, the woman was diagnosed with hyperemesis gravidarum and treated with regular IV fluids and the antinausea medication ondansetron. Her AST peaked at 132 U/L, as measured by the hospital’s analyzer, but by 20 weeks of gestation the symptoms had resolved. Her AST, measured on an outpatient basis this time using a Beckman Coulter AU5800 at Kaiser’s regional laboratory, was at a normal 38 U/L given that instrument’s reference range of 10–40 U/L.
At 33 weeks of gestation, the woman’s abdominal symptoms recurred, but the outpatient AST results continued to be normal. However, a paired specimen evaluated at the hospital laboratory showed an elevated AST. By 36 weeks of gestation, the woman reported continuous pain in the right upper quadrant of her abdomen. Specimens evaluated stat at the hospital laboratory all showed an elevated AST, with bile acids mildly elevated. Yet all other liver and pancreatic markers were normal. At 37 weeks of gestation, the woman underwent an uneventful elective caesarean section.
Due to the variances in the AST results, Dr. Baumann was asked to consult on the case. Serum aliquots sent to the Mayo Clinic and another reference laboratory—both of which use Roche Cobas instrumentation—also returned with discrepancies. Mayo Clinic flagged the specimen as having an elevated AST of 243 U/L, while the other reference laboratory flagged the sample as having a low AST of 8 U/L.
Even with two outside laboratories using the same instrumentation, the results reported were drastically different. With further investigation of the case, they were able to determine various patient and laboratory factors that caused the different results.
The reagent compositions were different. Mayo Clinic and the Kaiser hospital laboratory supplemented their reagent with pyridoxal-5-phosphate, the active form of vitamin B6, as a cofactor, while the Kaiser regional laboratory and the outside reference laboratory did not. The Mayo Clinic laboratory also tested for and identified a rare macroenzyme of AST in the patient’s serum, which is hypothesized to be more sensitive to B6 deficiency than “normal” AST.