Background Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay. Methods cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation. Results In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62–204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status. Conclusion We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.

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Background: Critical values are required to be phoned 24/7. Other abnormal results fall short of the thresholds used to define critical values and may only be required to be phoned during the day. Community-based requestors prefer not to be contacted unless a result is critical and contacting them requires substantial staff resource. It is common practice to add tests to requests to expedite diagnosis or clarify the significance of a particular result using algorithms. Methods: We devised algorithms for reflex addition of tests which allowed the differentiation of significantly abnormal results as either critical values or those that only require day phoning. Results: Algorithms identified 158 out of 309 tests as being critical (51%) over nine months. Reflex addition of serum bicarbonate identified 4% of serum glucose (24.9 -37.9 mmol/L) as critical. Use of estimated glomerular filtration rate by reflex addition of serum creatinine identified 68% of serum lithium (1.49 -1.99 mmol/L) as critical. Addition of serum potassium, calcium and magnesium identified 21% of serum digoxin (.2.49 nmol/L) as critical and addition of serum potassium and calcium to all samples with serum magnesium (,0.31 mmol/L) identified hypocalcaemia in all cases. The addition of serum creatinine and potassium as markers for rhabdomyolysis-induced acute renal failure did not help in the differentiation of serum creatine kinase . 4999 m/L. Conclusions: Use of reflex tests helped inform a phoning system based on the division of results into critical values and nonemergency abnormal values. This avoids disturbing requestors unnecessarily and conserves staff time at night.

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