Background Thoroughly investigating single patient result errors may identify systemic, large-scale testing errors. The laboratory observed an event where a revision to a Total Bile Acid (TBA, Diazyme Laboratories, Inc.) patient result following a 22S quality control (QC) failure displayed a larger than expected difference (52 to 5mcmol/L). TBA is primarily used for diagnosis and monitoring of intrahepatic cholestasis of pregnancy with results >10mcmol/L considered elevated. Retrospective review of result revisions following QC failures (3/15/2017-5/30/2023) revealed that 50%(20/40) yielded result differences of >10mcmol/L(>20SD based on assay imprecision). The aim of this study was to apply a systematic approach to i) estimate the rate of TBA errors, ii) ensure accurate result reporting during investigation period, iii) perform root cause analysis (RCA), and iv) determine corrective and preventative action(s). Methods Residual samples from TBA testing (6/24-7/5/2023) were retested(n=158), differences >+/-3.0mcmol/L or 15% were confirmed on an alternate analyzer, and reports were revised. Automated repeat testing of TBA samples >10mcmol/L was operationalized 7/6/2023. Initial and repeat TBA results were compared(n=448) and results differing by >+/-20% were remeasured on an alternate analyzer. RCA was conducted using a fishbone diagram. NaOH reagent probe washes were implemented for TBA and the error rate was re-assessed. Assays run prior to TBA samples with errors (n=15) were identified. To assess reagent carryover a residual serum pool (TBA ∼5mcmol/L) was aliquoted into 5 tubes in a sample rack. The first sample in the rack was programmed to run an assay suspected of causing carryover followed by 4 TBA measurements. Mean±standard deviation(SD) TBA concentrations were calculated. TBA was also measured in the liquid reagent for amylase, lipase, acetylcholinesterase (ACE) and fructosamine. Results Initial TBA retesting yielded no errors when initial TBA was ≤10mcmol/L(n=51). For samples with TBA >10mcmol/L(n=107), 9(8.4%) had differences exceeding criteria with 8/9 being revised to ≤10mcmol/L. Analysis of automated patient repeat data showed a 3.8%(17/448) error rate when initial TBA >10mcmol/L. After NaOH reagent probe washes were implemented, the error rate decreased to 0.7%(3/448). Assays run directly before an erroneously high TBA result included: lactate, fructosamine, soluble transferrin receptor(STFR), lipase, and ACE. A serum TBA pool(mean±SD=5.1±0.4 mcmol/L,n=15) measured 37.6±1.2mcmol/L(n=3) and 6.7±0.7mcmol/L(n=3) after lipase and fructosamine, respectively. No other assays demonstrated carryover. TBA in lipase reagent compartment B and C was 653 and 649mcmol/L, respectively, and 653mcmol/L in fructosamine reagent compartment B. Conclusions A single patient TBA result revision was investigated and led to identification of reagent carryover causing erroneously high TBA results on the Roche c502 analyzer. Automatic, real-time, repeat testing was implemented to prevent reporting incorrect patient results until RCA could identify the cause. Occurrence rate of erroneous high TBA results decreased from 3.8% to 0.7% after implementation of NaOH washes on the instruments. Carryover experiments confirmed that lipase and fructosamine assays cause carryover when run prior to a TBA sample due to measurable TBA in the reagent. The lab is pursuing moving the fructosamine and lipase reagent to the Roche Cobas c701 to prevent the issue.

中文翻译：

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A-088 在罗氏 c502 分析仪上使用迪亚酶总胆汁酸测定时出现的临床重大错误：调查结果错误发现了由试剂残留引起的新型大规模测试错误


背景 彻底调查单个患者的结果错误可能会发现系统性的、大规模的测试错误。实验室观察到一个事件，即 22S 质量控制 (QC) 失败后对总胆汁酸（TBA，Diazyme Laboratories, Inc.）患者结果的修订显示出大于预期的差异（52 至 5 mcmol/L）。 TBA主要用于诊断和监测妊娠期肝内胆汁淤积，结果>10mcmol/L视为升高。对 QC 失败后的结果修订进行回顾性审查 (3/15/2017-5/30/2023) 显示 50%(20/40) 产生 >10mcmol/L 的结果差异（>20SD 基于测定不精密度）。本研究的目的是应用系统方法来 i) 估计 TBA 错误率，ii) 确保调查期间准确的结果报告，iii) 执行根本原因分析 (RCA)，以及 iv) 确定纠正和预防措施（ s）。方法对TBA测试（2023年6月24日至7月5日）的剩余样品进行重新测试（n=158），在备用分析仪上确认差异>+/-3.0mcmol/L或15%，并对报告进行修订。 TBA 样品 >10mcmol/L 的自动重复测试于 2023 年 7 月 6 日投入运行。比较初始和重复 TBA 结果 (n=448)，并在备用分析仪上重新测量差异 >+/-20% 的结果。 RCA 使用鱼骨图进行。对 TBA 进行 NaOH 试剂探针清洗，并重新评估错误率。在 TBA 样品之前运行的测定被识别为有错误 (n=15)。为了评估试剂残留，将残留血清池（TBA~5mcmol/L）等分到样品架上的 5 个试管中。机架中的第一个样品被编程为运行疑似引起残留的检测，然后进行 4 次 TBA 测量。 计算平均值±标准差(SD) TBA浓度。还测量了液体试剂中淀粉酶、脂肪酶、乙酰胆碱酯酶 (ACE) 和果糖胺的 TBA。结果当初始TBA≤10mcmol/L时，初始TBA复测未出现错误（n=51）。对于TBA>10mcmol/L（n=107）的样品，9（8.4%）的差异超出标准，其中8/9被修改为≤10mcmol/L。自动患者重复数据分析显示，当初始 TBA >10mcmol/L 时，错误率为 3.8%(17/448)。实施NaOH试剂探针清洗后，错误率降低至0.7%(3/448)。在出现错误的高 TBA 结果之前直接进行的检测包括：乳酸、果糖胺、可溶性转铁蛋白受体 (STFR)、脂肪酶和 ACE。经脂肪酶和果糖胺处理后，血清 TBA 池（平均值±SD=5.1±0.4 mcmol/L，n=15）分别测得 37.6±1.2mcmol/L（n=3）和 6.7±0.7mcmol/L（n=3） 。没有其他检测显示残留。脂肪酶试剂隔室 B 和 C 中的 TBA 分别为 653 和 649 mcmol/L，果糖胺试剂隔室 B 中的 TBA 分别为 653 mcmol/L。 结论 对单个患者的 TBA 结果修订进行了调查，结果发现试剂残留造成了错误的高 TBA 结果。罗氏c502分析仪。实施自动、实时、重复测试，以防止在 RCA 查明原因之前报告错误的患者结果。对仪器进行 NaOH 清洗后，错误的高 TBA 结果的发生率从 3.8% 降至 0.7%。残留实验证实，在 TBA 样品之前进行脂肪酶和果糖胺测定时，由于试剂中可测量到 TBA，因此会导致残留。该实验室正在寻求将果糖胺和脂肪酶试剂转移到罗氏 Cobas c701 以防止出现此问题。