Citations

Context.— Misdiagnosis of antiphospholipid syndrome can occur owing to the wide diversity of antiphospholipid (aPL) assays and a lack of international calibrators and harmonized reference intervals. Objective.— To assess laboratory practices regarding reporting and establishing reference intervals for immunoglobulin (Ig) G/IgM anti-cardiolipin (aCL) and anti–beta-2 glycoprotein I (anti-β2GPI) assays. Design.— Supplemental questions related to reporting and establishing reference ranges for aPL assays were sent as part of the Antiphospholipid Antibody (ACL)-B 2019 College of American Pathologists (CAP) proficiency testing survey. The response rate and methods assessment details were determined, as well as qualitative and quantitative results for 3 test samples. Results.— The number of participants reporting results for IgG aCL (n = 489), IgM aCL (n = 476), IgG anti-β2GPI (n = 354), and IgM anti-β2GPI (n = 331) varied by antibody type. The enzyme-linked immunosorbent assay (ELISA) (up to 58.6%, 260 of 444) was the most used method; others included multiplex (from 18.9% to 23.9%), fluorescence enzyme immunoassay (14.4%–17.6%), and chemiluminescence immunoassay (6.5%–9.0%). More respondents reported quantitative than qualitative results, and manufacturer cutoff ranges were used by 92.9% and 94.2% of respondents for aCL and anti-β2GPI, respectively. Despite variation in the use of semiquantitative ranges, qualitative negative/positive reporting of the test samples achieved almost 100% consensus. Qualitative consensus was met in contrast to the wide range of quantitative results obtained for each analyte across different kits. Conclusions.— ELISA remains the most used method for detecting aPL antibodies, with most laboratories reporting quantitative results based on manufacturers' suggested reference ranges. The categorization of quantitative results as equivocal, weak positive, or positive for responders using kits from the same manufacturer was variable.

Context.— Consequences related to nicotine (NIC) use remain a major health concern, leading to demand for testing to detect NIC, metabolites such as cotinine (COT), and related tobacco alkaloids, including anabasine (ANAB). NIC-related testing is not standardized among laboratories, nor are there clinical or regulatory guidelines to inform decisions such as appropriate screening cutoffs or limits of quantitation. Objective.— To evaluate analytical performance and reporting practices of laboratories that perform NIC-related testing by reviewing participant responses to the Nicotine and Tobacco Alkaloid (NTA) Proficiency Testing Survey. Design.— NTA results were retrieved from 2017 (the first year of the survey) through 2020. Survey participants, methodologies, and results were evaluated for all analytes, and simulated grading was performed for COT. Additional data, including limits of quantitation, qualitative cutoffs, and reasons for testing, were reviewed. Results.— Participant growth was steady for qualitative COT testing. Participation was stable for NIC, ANAB, and quantitative COT testing. Overall, participants performed well on survey challenges. However, reporting thresholds were widely divergent, ranging from 10 to 3000 ng/mL and 0.5 to 300 ng/mL, respectively, for qualitative and quantitative COT testing. Screening cutoffs were as high as 100 ng/mL for ANAB and 1000 ng/mL for NIC. Conclusions.— Although participating laboratories performed well on the NTA Survey, the wide diversity of qualitative and quantitative reporting thresholds creates substantial risk for misinterpretation of results, and could lead to analytical concerns such as excessively high false-negative or false-positive rates. NIC-related testing would benefit from evidence-based guidelines to drive standardization of reporting.