Clinical trials and guidelines support the use of very low high-sensitivity cardiac troponin (hs-cTn) results to rule-out a myocardial infarction (MI) ( 1) Jaffe A.S. Body R. Mills N.L. Aakre K.M. Collinson P.O. Saenger A. Hammarsten O. Wereski R. Omland T. Sandoval Y. Ordonez-Llanos J. Apple F.S. IFCC Committee on Cardiac Bio-Markers. Single Troponin Measurement to Rule Out Myocardial Infarction: JACC Review Topic of the Week. J Am Coll Cardiol. 2023 Jul 4; 82: 60-69 Crossref Scopus (7) Google Scholar ). The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Biomarkers committee, through a modeling approach, suggests assays need to have a lower limit near 3 ng/L and an analytical variation of 10% below 7 ng/L if these low values are to perform consistently in practice ( 2) Aakre K.M. Apple F.S. Mills N.L. Meex S.J.R. Collinson P.O. International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB)Lower Limits for Reporting High-Sensitivity Cardiac Troponin Assays and Impact of Analytical Performance on Patient Misclassification. Clin Chem. 2023 Dec; 15hvad185 Google Scholar ). Our objectives for the present study were to assess: i) if any type of instrument or individual instrument could achieve a coefficient of variation (CV) of ≤10% at very low hs-cTn cut-offs (i.e., targets) recommended in clinical pathways; ii) the frequency of results at the hs-cTn target, above the target and below the target, with the latter group representing potential misclassification to the low risk group where the target level would in the intermediate risk range.

BACKGROUND:An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays.METHODS:Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated.RESULTS:The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %).CONCLUSIONS:The number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

A multicentre prospective observational study (36 sites in 8 Canadian provinces), imbedded in the CODE-MI trial, had clinical laboratories at these sites test 3 samples (normal, female 99th-percentile, and male 99th-percentile concentrations) monthly for 1 year on 67 instruments, producing 2142 results from 6 distinct troponin assays. Mean differences varied per assay with maximum values being & PLUSMN; 4, & PLUSMN; 8, and & PLUSMN; 9 ng/L for the normal, female 99th-percentile, and male 99th-percentile sample, respectively. Using a pragmatic approach, combining all assays, the maximum analytic result variation was & PLUSMN; 3 ng/L for target concentrations less than 10 ng/L and & PLUSMN; 30% at concen-trations slightly above.

Background: Scurvy is a rare entity in developed countries and the diagnosis may often be delayed resulting in unnecessary investigations and/or potentially severe complications. A recent increase in the number of patients diagnosed with scurvy in our hematology clinics indicated the need to review the literature on the diagnosis and optimal management of similar patients. Methods: We conducted a retrospective chart review of patients referred to hematology at our tertiary care centre between 2010 and 2018, who were ultimately diagnosed with scurvy. Data collected from electronic medical records included baseline characteristics, clinical features on presentation, bloodwork results from initial consultation, treatment plan as well as response to treatment. Findings: Twenty-two adults patient had a diagnosis of scurvy with a mean vitamin C level of 6 mu mol/L. Iron deficiency anemia (54%) and gastrointestinal disorders (54%) were the most common comorbidities noted in our cohort. Proton-pump inhibitors use was noted in 54% of patients. Bleeding (45%) and bruising (45%) were the most commonly reported clinical features. Eleven patients received oral supplementation, five had intravenous (IV) vitamin C and six were not treated. Two patients required a transition from oral to IV supplementation. Vitamin C dosing ranged between 250 and 2000 mg and the frequency varied from daily for oral therapy to every few weeks or months for IV. Interpretation: Awareness of scurvy and its associated risk factors and clinical presentation is important in the evaluation of a patient with bleeding tendency. Treatment plan should be individualized, and a careful review of patients' diet, medial history and medications is warranted.