Clinical biochemistry最新文献_第9页

Minimizing high sensitivity troponin T delta variation at low concentration using BD Barricor blood collection tube 使用BD Barricor采血管最小化低浓度高灵敏度肌钙蛋白T δ变化

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-29 DOI: 10.1016/j.clinbiochem.2025.111003

Albert K.Y. Tsui , Jialin Qiu , Isolde Seiden-Long , George Cembrowski

Objective

Reproducible low troponin concentrations from high-sensitivity troponin (hs-cTn) assays are paramount to accurate risk determination in the accelerated diagnostic pathway. Total variation consists of pre-analytical, analytical and biological components. While analytical and biological variations cannot be readily modifiable, minimizing pre-analytical variation is desirable and potentially attainable. The BD Barricor collection tube has previously been demonstrated to reduce pre-analytical variation in test results. The goal of the study is to determine whether BD Barricor tubes provide more reproducible hs-cTnT results compared to plasma separator tubes (PST) at concentrations ≤ 20 ng/L.

Methods

Paired intra-patient hs-cTnT results collected less than 1 h apart in the emergency department were retrospectively analyzed from nine urban hospitals which primarily use either PST (n = 336 pairs) or Barricor (n = 327 pairs) collection tubes for troponin. Total variation of the replicated measurements was calculated for hs-cTnT ≤ 20 ng/L. The numbers of paired intra-patient samples were grouped based on decisive absolute delta thresholds as indicated by the European Society of Cardiology 0/1 h algorithm; delta < 3 ng/L, 3–4 ng/L, ≥5 ng/L.

Results

The total testing variation for hs-cTnT collected in PST is 14.8 % while Barricor is 8.6 % for hs-cTnT ≤ 20 ng/L. The proportion of delta values < 3 ng/L between the intra-patient replicates is 80.4 % (95 % CI: 75.7–84.5 %) in PST compared to 95.4 % (95 % CI: 92.5–97.4 %) in Barricor (p < 0.001). Median time for serial sampling in PST is 41 min (IQR:18–53) and Barricor is 45 min (IQR 23–54).

Conclusion

The use of Barricor tubes demonstrated reproducible and less variable hs-cTnT replicates at concentration ≤ 20 ng/L when compared to a hospital that does not use Barricor tubes.

目的通过高灵敏度肌钙蛋白（hs-cTn）检测产生的低肌钙蛋白浓度对加速诊断途径中准确确定风险至关重要。总变异由分析前成分、分析成分和生物成分组成。虽然分析和生物变异不能轻易改变，但尽量减少分析前变异是可取的，也是可能实现的。BD Barricor收集管先前已被证明可以减少分析前测试结果的变化。该研究的目的是确定在浓度≤20 ng/L时，BD Barricor管是否比等离子分离器管（PST）提供更可重复的hs-cTnT结果。方法回顾性分析9家主要使用PST （n = 336对）或Barricor （n = 327对）肌钙蛋白收集管的城市医院急诊科间隔不到1 h采集的西班牙患者hs-cTnT结果。计算hs-cTnT≤20 ng/L时重复测量的总变异。配对患者内样本的数量根据欧洲心脏病学会0/1 h算法确定的绝对delta阈值进行分组；3 ng/L、3 - 4 ng/L、≥5 ng/L。结果PST法检测hs-cTnT的总变异率为14.8%，而Barricor法检测hs-cTnT≤20 ng/L时变异率为8.6%。在PST中，3 ng/L的δ值比例为80.4% (95% CI: 75.7 - 84.5%)，而在Barricor中为95.4% (95% CI: 92.5 - 97.4%) （p < 0.001）。PST连续采样的中位时间为41分钟（IQR: 18-53）， Barricor为45分钟（IQR: 23-54）。结论与不使用Barricor管的医院相比，使用Barricor管的hs-cTnT在浓度≤20 ng/L时重复性好，变异少。

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引用次数: 0

Comparison of capillary dried blood spot and capillary microtubes with venous immunoglobulin G levels for routine diagnostics 毛细管干血斑和毛细管微管与静脉免疫球蛋白G常规诊断的比较

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-25 DOI: 10.1016/j.clinbiochem.2025.110996

S.L. Boland , M.J.H. Doeleman , L.G.E. Hofstee , L. Soels , T.S.Q. Visser , S. de Roock , D. Hamann , J.M. van Montfrans , W.M. Tiel Groenestege

Background and aims

Patients with primary antibody deficiencies receiving immunoglobulin replacement therapy require frequent monitoring of immunoglobulin G (IgG) levels. Capillary IgG measurements from dried blood spots (DBS) or microtubes offer several advantages over samples obtained by venipuncture, including facilitating remote self-sampling. However, the validity of this alternative method is still unknown. We evaluated the comparability of IgG levels measured in venous samples with capillary blood samples collected on DBS cards and in microtubes.

Methods

Paired venous and capillary finger-stick DBS and microtube samples were collected from 100 patients. IgG was extracted from DBS with phosphate buffered saline and measured with a Siemens Atellica CH. For method comparison we performed Deming regression analysis. Absolute mean bias and limits of agreement were calculated with Bland-Altman analysis. The method comparison followed the Clinical Laboratory Improvement Amendments’ (CLIA) recommended approach, but stricter limits proposed by the EFLM were applied. Relative mean differences were compared to a 10.9 % total allowable error (TEa).

Results

Method comparison of venous versus capillary DBS samples resulted in an R of 0.77. Mean bias was 0.23 g/L with limits of agreement of −4.06 g/L to 4.53 g/L. Method comparison of venous versus capillary microtube samples resulted in an R of 1.00. Mean bias was −0.11 g/L with −0.67 g/L to 0.46 g/L limits of agreement. Relative mean differences were 2.2 % for DBS sampling and −0.6 % for capillary sampling, both fall within 10.9 % TEa and CLIA criteria.

Conclusion

IgG measurements from DBS demonstrated insufficient correlation and excessively broad limits of agreement, making it unsuitable for accurately determining IgG levels. This result hampers implementation of DBS in routine diagnostics. Conversely, capillary microtube samples demonstrated a strong correlation and narrow limits of agreement, which makes them a viable alternative to venipuncture.

背景和目的接受免疫球蛋白替代治疗的一抗缺乏患者需要经常监测免疫球蛋白G （IgG）水平。从干血点（DBS）或微管中测量毛细管IgG比通过静脉穿刺获得的样本有几个优点，包括便于远程自采样。然而，这种替代方法的有效性仍然未知。我们评估了静脉样本中IgG水平与DBS卡和微管中收集的毛细血管血液样本的可比性。方法采集100例患者静脉、毛细血管指棒DBS及微管标本。用磷酸盐缓冲盐水从DBS中提取IgG，并用西门子Atellica CH进行测量。为了比较方法，我们进行了Deming回归分析。采用Bland-Altman分析计算绝对平均偏倚和一致限。方法比较遵循临床实验室改进修正案（CLIA）推荐的方法，但应用了EFLM提出的更严格的限制。相对平均差异比较10.9%的总允许误差（TEa）。结果静脉DBS与毛细血管DBS比较，R为0.77。平均偏差为0.23 g/L，一致性限为- 4.06 g/L至4.53 g/L。方法静脉微管与毛细血管微管样品比较，R为1.00。平均偏差为- 0.11 g/L，一致性限为- 0.67 g/L至0.46 g/L。DBS取样的相对平均差异为2.2%，毛细管取样的相对平均差异为- 0.6%，均在TEa和CLIA标准的10.9%之内。结论DBS检测IgG相关性不足，一致性范围过广，不适合准确测定IgG水平。这一结果阻碍了DBS在常规诊断中的实施。相反，毛细血管微管样品显示出很强的相关性和狭窄的一致性限制，这使它们成为静脉穿刺的可行替代方案。

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引用次数: 0

An improved and economical LLE-LC/MS method for quantifying phosphatidylethanol: Identification and separation of isotopic cross-talk in clinical alcohol testing 一种改进且经济的液相色谱-质谱法定量磷脂酰乙醇：临床酒精检测中同位素串扰的鉴定与分离

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-22 DOI: 10.1016/j.clinbiochem.2025.110994

Naga Veera Yerra, Christopher Pini, Carlos Cordon-Cardo, Damodara Rao Mendu

Objective

Phosphatidylethanol (PEth) is a group of phospholipids formed in the presence of ethanol on the red blood cell membrane. Due to their stability in blood for 3–4 weeks, they have become reliable direct biomarkers for long-term monitoring of alcohol use. This study aimed to develop and validate a robust, high-throughput liquid chromatography and tandem mass spectrometry (LC-MS/MS) method for the routine clinical quantification of the two most common PEth homologues, PEth 16:0/18:1 (POPEth) and PEth 16:0/18:2 (PLPEth), while addressing common analytical challenges.

Methods

An established quantification method employing liquid–liquid extraction was used with optimized LC-MS/MS parameters. The method was validated for correlation studies, precision, analytical measurement range, analytical sensitivity, analytical specificity, carryover, dilution linearity, stability, matrix effect and extraction recovery, with specific attention to eliminating isotopic cross-talk and chromatographic interferences. A method comparison was performed using specimens analyzed by an external reference laboratory.

Results

The method demonstrated excellent linearity for both POPEth and PLPEth across the analytical measurement range (10–2000 ng/mL), with correlation coefficients (r²) of 0.99. Intra- and inter-assay precision values were within ± 10 % coefficient of variation. Recovery yields ranged from 78-85 %. The optimized method resolved isotopic cross-talk and exhibited no carryover. Comparison with an external laboratory showed strong correlation for both homologues (slopes of 0.979 and 1.049; r² = 0.99).

Conclusion

We developed and validated a sensitive and specific LC-MS/MS method for the quantification of POPEth and PLPEth. The assay provides improved recovery, eliminates isotopic cross-talk, shows no carryover, and is suitable for high-throughput clinical laboratories. This method enables reliable and cost-effective monitoring of alcohol use in routine clinical practice.

目的：磷脂酰乙醇（PEth）是在乙醇存在下在红细胞膜上形成的一组磷脂。由于它们在血液中的稳定性为3-4周，它们已成为长期监测酒精使用情况的可靠直接生物标志物。本研究旨在开发和验证一种强大的高通量液相色谱-串联质谱（LC-MS/MS）方法，用于常规临床定量两种最常见的PEth同源物，PEth 16:0/18:1 （POPEth）和PEth 16:0/18:2 (PLPEth)，同时解决常见的分析挑战。方法采用优化的LC-MS/MS参数，建立液液萃取定量方法。验证了该方法的相关性研究、精密度、分析测量范围、分析灵敏度、分析特异性、携带、稀释线性、稳定性、基质效应和提取回收率，特别注意消除同位素串扰和色谱干扰。采用外部参比实验室分析的标本进行方法比较。结果POPEth和PLPEth在10 ~ 2000 ng/mL的分析范围内呈良好的线性关系，相关系数（r2）为0.99。测定内和测定间的精密度值在±10%变异系数内。回收率为78 ~ 85%。优化后的方法解决了同位素串扰，无遗留现象。与外部实验室比较，两种同源物具有较强的相关性（斜率分别为0.979和1.049,r2 = 0.99）。结论建立了一种灵敏、特异的hplc -MS/MS定量方法。该检测方法提高了回收率，消除了同位素串扰，无残留，适用于高通量临床实验室。这种方法能够在常规临床实践中可靠和具有成本效益地监测酒精使用情况。

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引用次数: 0

Defining a clinically relevant thyroglobulin antibody interference threshold for high-sensitivity thyroglobulin immunoassays: a single institution case study 定义高灵敏度甲状腺球蛋白免疫测定的临床相关甲状腺球蛋白抗体干扰阈值：单一机构案例研究

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-21 DOI: 10.1016/j.clinbiochem.2025.110995

Simmi Patel , Octavia M. Peck Palmer , Chanda B. Lay , Kathleen Mulvey , Michael R. Shurin , Sarah E. Wheeler

Background

The interpretation of serum thyroglobulin (Tg) levels in differentiated thyroid cancer is complicated by interference from thyroglobulin antibodies (TgAb) and there is no standardized threshold to determine interference. Following implementation of a new instrument, we observed increased TgAb-positive samples which reflex to alternate send-out Tg methods with reduced analytic sensitivity but which are more robust to TgAb interference. This resulted in fewer patients having detectable Tg for monitoring, longer turnaround times, and higher costs. We hypothesized that the TgAb assay limit of detection (LOD) was lower than the clinically meaningful interference threshold.

Methods

We analyzed 119 serum specimens with an electrochemiluminescent TgAb immunoassay (ECLIA-TgAb) ≥ 10 IU/mL, comparing TgAb measurements by radioimmunoassay (RIA-TgAb) and Tg levels measured via immunometric assay (IMA-Tg) and RIA (RIA-Tg; reference method), and clinical adjudication of discrepant samples.

Results

Of ECLIA-TgAb specimens above the LOD (10 IU/mL), 30 % were positive by RIA-TgAb. Increasing the ECLIA-TgAb threshold to 20 IU/mL improved concordance to 90 %. A 20 IU/mL threshold optimized qualitative agreement between IMA-Tg and RIA-Tg (95 %). Retrospective chart review of patient diagnosis and treatment indicated that there would be no change in patient management with the revised threshold.

Conclusions

We found that an ECLIA-TgAb threshold of 20 IU/mL allowed more patients to be followed by the high sensitivity IMA-Tg method with no change to clinical decision-making, reducing send-out testing by 66 %. This approach offers an accessible and practical strategy for individual laboratories to define clinically appropriate TgAb thresholds to maximize the samples eligible for highly sensitive Tg measurement.

分化型甲状腺癌血清甲状腺球蛋白（Tg）水平的解释由于甲状腺球蛋白抗体（TgAb）的干扰而变得复杂，并且没有标准的阈值来确定干扰。随着新仪器的实施，我们观察到增加的TgAb阳性样品，这些样品反射到交替的发送Tg方法，分析灵敏度降低，但对TgAb干扰更强。这导致更少的患者可检测到Tg监测，更长的周转时间和更高的成本。我们假设TgAb检测限（LOD）低于临床有意义的干扰阈值。方法采用电化学发光TgAb免疫分析法(ECLIA-TgAb)≥10 IU/mL对119例血清标本进行分析，比较放射免疫分析法（RIA-TgAb）测定的TgAb与免疫分析法（IMA-Tg）和RIA （RIA-Tg；参比法）测定的Tg水平，并对差异样本进行临床判定。结果ECLIA-TgAb在LOD （10 IU/mL）以上的标本中，30%呈RIA-TgAb阳性。将ECLIA-TgAb阈值提高到20 IU/mL，一致性提高到90%。20 IU/mL的阈值优化了IMA-Tg和RIA-Tg的定性一致性（95%）。患者诊断和治疗的回顾性图表回顾表明，修订后的阈值不会改变患者的管理。我们发现，ECLIA-TgAb阈值为20 IU/mL，可以让更多的患者采用高灵敏度的IMA-Tg方法进行随访，而临床决策没有改变，将发送检测减少了66%。这种方法为个别实验室提供了一种方便和实用的策略，以确定临床上合适的TgAb阈值，以最大限度地提高高灵敏度Tg测量的样品资格。

{"title":"Defining a clinically relevant thyroglobulin antibody interference threshold for high-sensitivity thyroglobulin immunoassays: a single institution case study","authors":"Simmi Patel , Octavia M. Peck Palmer , Chanda B. Lay , Kathleen Mulvey , Michael R. Shurin , Sarah E. Wheeler","doi":"10.1016/j.clinbiochem.2025.110995","DOIUrl":"10.1016/j.clinbiochem.2025.110995","url":null,"abstract":"<div><h3>Background</h3><div>The interpretation of serum thyroglobulin (Tg) levels in differentiated thyroid cancer is complicated by interference from thyroglobulin antibodies (TgAb) and there is no standardized threshold to determine interference. Following implementation of a new instrument, we observed increased TgAb-positive samples which reflex to alternate send-out Tg methods with reduced analytic sensitivity but which are more robust to TgAb interference. This resulted in fewer patients having detectable Tg for monitoring, longer turnaround times, and higher costs. We hypothesized that the TgAb assay limit of detection (LOD) was lower than the clinically meaningful interference threshold.</div></div><div><h3>Methods</h3><div>We analyzed 119 serum specimens with an electrochemiluminescent TgAb immunoassay (ECLIA-TgAb) ≥ 10 IU/mL, comparing TgAb measurements by radioimmunoassay (RIA-TgAb) and Tg levels measured via immunometric assay (IMA-Tg) and RIA (RIA-Tg; reference method), and clinical adjudication of discrepant samples.</div></div><div><h3>Results</h3><div>Of ECLIA-TgAb specimens above the LOD (10 IU/mL), 30 % were positive by RIA-TgAb. Increasing the ECLIA-TgAb threshold to 20 IU/mL improved concordance to 90 %. A 20 IU/mL threshold optimized qualitative agreement between IMA-Tg and RIA-Tg (95 %). Retrospective chart review of patient diagnosis and treatment indicated that there would be no change in patient management with the revised threshold.</div></div><div><h3>Conclusions</h3><div>We found that an ECLIA-TgAb threshold of 20 IU/mL allowed more patients to be followed by the high sensitivity IMA-Tg method with no change to clinical decision-making, reducing send-out testing by 66 %. This approach offers an accessible and practical strategy for individual laboratories to define clinically appropriate TgAb thresholds to maximize the samples eligible for highly sensitive Tg measurement.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"139 ","pages":"Article 110995"},"PeriodicalIF":2.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analytical performance and clinical evaluation of CL AIA-PACK® hs-E2, a high-sensitivity estradiol sandwich immunoassay using an anti-immunocomplex antibody CL AIA-PACK®hs-E2是一种使用抗免疫复合物抗体的高灵敏度雌二醇三明治免疫分析法，其分析性能和临床评价

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-18 DOI: 10.1016/j.clinbiochem.2025.110993

Satoshi Fujimura , Yoko Usami , Akari Yamamoto , Nau Ishimine

Introduction

The CL AIA-PACK® hs-E2 (hs-E2) is a high-sensitivity estradiol (E2) sandwich immunoassay employing an anti-immunocomplex antibody. This study aimed to evaluate its analytical performance and clinical utility at low concentration ranges relevant to aromatase inhibitor therapy and pediatric endocrinology, where accurate E2 measurement is clinically important.

Methods

The hs-E2 assay was evaluated for its precision, linearity, sensitivity, and interference. Its performance was compared with a conventional competitive immunoassay (Elecsys® E2) and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Estradiol levels were measured in patients with estrogen receptor-positive breast cancer receiving selective estrogen receptor modulator or aromatase inhibitor therapy to assess clinical applicability.

Results

The assay showed excellent precision (CVs < 6.4 %) and linearity across a broad concentration range. The limit of detection and limit of quantification were 4.84 and 7.11 pmol/L (10 % CV), respectively. Conjugated bilirubin induced a mild concentration-dependent decrease in measured E2 values. The hs-E2 assay showed a strong correlation with LC-MS/MS, even at low concentration ranges (r = 0.998), while Elecsys showed a weaker correlation below 147 pmol/L. In breast cancer patients, hs-E2 revealed significant differences in E2 levels across treatment groups, which were not detectable by the Elecsys assay.

Conclusions

The hs-E2 immunoassay using an anti-immunocomplex antibody exhibited superior analytical sensitivity and precision at low concentration ranges to conventional methods. Its strong agreement with LC-MS/MS and enhanced clinical discrimination support its utility in monitoring E2 levels in hormone-treated breast cancer patients and other low-E2 clinical conditions.

CL AIA-PACK®hs-E2 （hs-E2）是一种采用抗免疫复合物抗体的高灵敏度雌二醇（E2）三明治免疫分析法。本研究旨在评估其在芳香酶抑制剂治疗和儿科内分泌学相关的低浓度范围内的分析性能和临床应用，其中准确的E2测量在临床上很重要。方法对hs-E2测定法的精密度、线性度、灵敏度和干扰度进行评价。将其性能与传统的竞争性免疫分析法（Elecsys®E2）和液相色谱-串联质谱法（LC-MS/MS）进行比较。在接受选择性雌激素受体调节剂或芳香化酶抑制剂治疗的雌激素受体阳性乳腺癌患者中测量雌二醇水平以评估其临床适用性。结果该方法精密度高（CVs < 6.4%），在较宽的浓度范围内线性良好。检测限和定量限分别为4.84和7.11 pmol/L （10% CV）。偶联胆红素诱导E2测量值轻度浓度依赖性降低。在低浓度范围内，hs-E2与LC-MS/MS具有较强的相关性（r = 0.998），而在147 pmol/L以下，Elecsys的相关性较弱。在乳腺癌患者中，hs-E2显示了不同治疗组E2水平的显著差异，这是Elecsys检测无法检测到的。结论采用抗免疫复合物抗体对hs-E2进行免疫分析，在低浓度范围内具有较高的灵敏度和精密度。它与LC-MS/MS的强一致性和增强的临床鉴别支持其在激素治疗的乳腺癌患者和其他低E2临床条件下监测E2水平的实用性。

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引用次数: 0

Gaps in guideline adherence: evaluating HLA-B*57:01 screening for abacavir sensitivity and the implementation of evidence-based HIV care 指南依从性的差距：评估HLA-B*57:01筛查阿巴卡韦敏感性和基于证据的艾滋病毒护理的实施

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-18 DOI: 10.1016/j.clinbiochem.2025.110992

Lisa V. Kalman , Yang Xia , Ya-Lin A. Huang , Kate Buchacz , Rex Astles , Jesse O’Shea

Objective

Approximately 5–8 % of the population carries the HLA-B*57:01 allele, which increases the risk of severe hypersensitivity reactions to abacavir. Current guidelines and an FDA black box warning recommend HLA-B*57:01 screening for all patients before starting abacavir. We assessed the proportion of patients who undergo screening before initiating abacavir to evaluate adherence to guidelines.

Design

A retrospective cohort study using national IQVIA® PharMetrics Plus reimbursement data.

Methods

Data from the 2014-2022 IQVIA® PharMetrics Plus March 2023 dataset were analyzed. We identified patients aged ≥ 18 years who were newly prescribed abacavir, with ≥ 12 months of continuous enrollment before their first abacavir prescription. We examined the proportion of individuals who received HLA-B*57:01 screening any time before their initial abacavir prescription and conducted a multivariable logistic regression analysis on the receipt of HLA-B*57:01 screening adjusting for sex, age, year, and region.

Results

We identified 7,391 patients newly prescribed abacavir between 2014 and 2022. Approximately 46 % received an HLA-B*57:01 screen before initiation of abacavir. Annual screening rates ranged from 44 % to 50 % between 2015 and 2018 and dropped to 17 % by 2022. Screening was less likely to occur after 2018, compared to earlier in the study period, and more likely for younger as well as male patients.

Conclusions

These findings highlight broader challenges in HIV guideline adherence, emphasizing the need for ongoing evaluation and systematic interventions to improve implementation and patient safety.

目的：大约5- 8%的人群携带HLA-B*57:01等位基因，这增加了阿巴卡韦严重超敏反应的风险。目前的指南和FDA黑框警告建议在开始使用阿巴卡韦之前对所有患者进行HLA-B*57:01筛查。我们评估了在开始阿巴卡韦治疗前接受筛查的患者比例，以评估其对指南的依从性。设计采用国家IQVIA®PharMetrics Plus报销数据进行回顾性队列研究。方法：分析2014-2022年IQVIA®PharMetrics Plus 2023年3月数据集的数据。我们确定了年龄 ≥ 18 岁的新开阿巴卡韦的患者，在首次开阿巴卡韦处方前，患者连续入组时间 ≥ 12 个月。我们检查了在初始阿巴卡韦处方前接受HLA-B*57:01筛查的个体比例，并对接受HLA-B*57:01筛查的个体进行了多变量logistic回归分析，调整了性别、年龄、年份和地区。结果：我们在2014年 至 2022年间确定了7391名新开阿巴卡韦的患者。大约46% %在开始阿巴卡韦之前接受了HLA-B*57:01筛选。2015年至2018年间，年筛查率从44% %到50% %不等，到2022年降至17% %。与研究期间的早期相比，2018年之后进行筛查的可能性较小，年轻患者和男性患者更有可能进行筛查。结论：这些发现突出了艾滋病毒指南遵守方面的更广泛挑战，强调需要进行持续评估和系统干预，以改善实施和患者安全。

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引用次数: 0

Ionized magnesium—the forgotten strong ion in pediatric critical care 离子化镁——在儿科重症监护中被遗忘的强离子。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-15 DOI: 10.1016/j.clinbiochem.2025.110991

Guido Filler

引用次数: 0

Capillary electrophoresis mis-anchoring in a case of Hb Hope with HbE HbE合并Hb Hope的毛细管电泳错误锚定1例

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-14 DOI: 10.1016/j.clinbiochem.2025.110990

Victoria Higgins , Natalia Volodko , Michelle L. Parker , Mathew P. Estey , Dustin Proctor , Lily Olayinka , Ashley Newbigging , Pierre Bordeleau , Maggie Powell

Background

Capillary electrophoresis is a widely used method for hemoglobin (Hb) fraction separation and relative quantitation, where pre-defined Hb peaks (typically HbA and HbA2) act as reference points to “anchor” the electropherogram and define migration zones. In cases lacking HbA or involving variants with migration patterns similar to HbA or HbA2, mis-anchoring can occur–leading to incorrect zoning of Hb variants. This presents a diagnostic challenge, where follow-up investigations, often including molecular testing, are required to establish an accurate diagnosis.

Case Report

We report a case of a 43-year-old Thai female who underwent hemoglobinopathy investigation for microcytic anemia. Capillary electrophoresis showed peaks in the HbA (70.8%), HbA2 (24.4%), and HbC (2.9%) zones, as well as two small peaks in the Z11 (0.9%) and HbD (1.0%) zones. Gel electrophoresis at acid pH showed a band in the HbA position and one slightly anodal to the HbF position and at alkaline pH showed a band in the HbC/E position and another slightly anodal to the HbA position. HBB sequencing identified heterozygosity for the pathogenic HbE and clinically benign Hb Hope variants. HBA PCR detected a single alpha globin gene deletion (αα/α-3.7), consistent with alpha thalassemia silent carrier. Reinterpretation of the electropherogram showed that Hb Hope and HbE mis-anchored as HbA and HbA2, respectively, due to their similar migration deltas.

Conclusion

This is the first documented case of compound heterozygosity for Hb Hope and HbE characterized by capillary electrophoresis. It highlights how beta chain variants with similar migration spacing to HbA and HbA2 can mis-anchor, emphasizing the need for molecular testing when results are unclear. Definitive testing helps avoid diagnostic misclassification and ensure accurate interpretation in complex hemoglobinopathy cases.

毛细管电泳是一种广泛使用的血红蛋白（Hb）分离和相对定量方法，其中预定义的Hb峰（通常是HbA和HbA2）作为参考点来“锚定”电泳并定义迁移区。在缺乏HbA或涉及具有与HbA或HbA2相似迁移模式的变体的情况下，可能会发生错误的锚定-导致Hb变体的不正确分区。这对诊断提出了挑战，需要后续调查，通常包括分子检测，以建立准确的诊断。我们报告一例43岁泰国女性，因小细胞性贫血接受血红蛋白病调查。毛细管电泳在HbA区（70.8%）、HbA2区（24.4%）和HbC区（2.9%）有峰，在Z11区（0.9%）和HbD区（1.0%）有两个小峰。在酸性pH下，凝胶电泳显示一条条带位于HbA位置，一条条带与HbF位置轻微阳极化；在碱性pH下，凝胶电泳显示一条条带位于HbC/E位置，另一条条带与HbA位置轻微阳极化。HBB测序鉴定出致病性HbE和临床良性Hb Hope变异的杂合性。HBA PCR检测到单个α珠蛋白基因缺失（αα/α-3.7），与α地中海贫血沉默携带者一致。对电泳图的重新解释表明，Hb Hope和HbE由于其相似的迁移三角洲，分别错误地锚定为HbA和HbA2。结论这是首次用毛细管电泳方法鉴定Hb Hope和HbE的复合杂合性。该研究强调了与HbA和HbA2具有相似迁移间隔的β链变异是如何错误锚定的，强调了在结果不明确时进行分子测试的必要性。明确的检测有助于避免诊断错误分类，并确保准确解释复杂的血红蛋白病病例。

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引用次数: 0

Critical role of laboratory and multidisciplinary strategies in the early diagnosis of acquired haemophilia a for life-saving management 实验室和多学科策略在获得性血友病a的早期诊断和救生管理中的关键作用。

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-14 DOI: 10.1016/j.clinbiochem.2025.110988

R. Belardi , M. Emili , F.G. Viola , S. Velocci , M. Baldetti , M. Minieri , M. Pieri , E. Picchi , D. Morosetti , S. Bernardini , A. Terrinoni

Background

Acquired haemophilia A (AHA) is a rare but potentially life-threatening autoimmune disorder characterized by the development of autoantibodies against coagulation factor VIII (FVIII). It manifests with spontaneous, severe bleeding in patients without a personal or family history of bleeding disorders. Early recognition and rapid treatment are crucial to reduce morbidity and mortality.

Case presentation

Here we describe two cases of AHA in elderly female patients with no prior history of coagulopathy. The first case involved an 81-year-old woman presenting with extensive spontaneous haematomas and severe anaemia. Laboratory findings revealed an isolated prolonged activated partial thromboplastin time (aPTT), undetectable FVIII activity, and the presence of a low-titre FVIII inhibitor (2.24 BU/mL). Treatment with recombinant activated factor VII (rFVIIa) and corticosteroids led to clinical improvement and inhibitor reduction. The second case concerned an 85-year-old woman who developed severe haemorrhagic manifestations following ureteric stenting. Coagulation studies showed markedly prolonged aPTT and a high-titre FVIII inhibitor (165 BU/mL). Despite initiation of immunosuppressive therapy the patient experienced fatal complications due to uncontrolled bleeding and multi-organ failure.

Conclusions

These cases underscore the importance of considering a possible AHA in patients with isolated aPTT prolongation and unexplained bleeding. Punctual laboratory diagnosis, including mixing studies and FVIII inhibitor assays, is essential for early life-saving interventions. Multi-disciplinary management and rapid initiation of haemostatic and immunosuppressive therapies are key to improving outcomes in this challenging condition.

背景：获得性血友病A （AHA）是一种罕见但可能危及生命的自身免疫性疾病，其特征是产生针对凝血因子VIII （FVIII）的自身抗体。在没有出血性疾病的个人或家族病史的患者中表现为自发性严重出血。早期发现和快速治疗对于降低发病率和死亡率至关重要。病例介绍：在这里，我们描述了两例老年女性无凝血病史的AHA患者。第一个病例涉及一名81岁妇女，表现为广泛的自发性血肿和严重贫血。实验室结果显示，分离的活化部分凝血活素时间延长（aPTT），检测不到FVIII活性，存在低滴度FVIII抑制剂（2.24 BU/mL）。重组活化因子VII （rFVIIa）和皮质类固醇治疗导致临床改善和抑制剂减少。第二个病例涉及一名85岁妇女，她在输尿管支架置入后出现严重出血症状。凝血研究显示aPTT明显延长，高滴度FVIII抑制剂（165 BU/mL）。尽管开始了免疫抑制治疗，但由于无法控制的出血和多器官衰竭，患者出现了致命的并发症。结论：这些病例强调了考虑孤立aPTT延长和不明原因出血患者可能发生AHA的重要性。及时的实验室诊断，包括混合研究和FVIII抑制剂测定，对于早期挽救生命的干预措施至关重要。多学科管理和快速启动止血和免疫抑制治疗是改善这种具有挑战性的情况的关键。

{"title":"Critical role of laboratory and multidisciplinary strategies in the early diagnosis of acquired haemophilia a for life-saving management","authors":"R. Belardi , M. Emili , F.G. Viola , S. Velocci , M. Baldetti , M. Minieri , M. Pieri , E. Picchi , D. Morosetti , S. Bernardini , A. Terrinoni","doi":"10.1016/j.clinbiochem.2025.110988","DOIUrl":"10.1016/j.clinbiochem.2025.110988","url":null,"abstract":"<div><h3>Background</h3><div>Acquired haemophilia A (AHA) is a rare but potentially life-threatening autoimmune disorder characterized by the development of autoantibodies against coagulation factor VIII (FVIII). It manifests with spontaneous, severe bleeding in patients without a personal or family history of bleeding disorders. Early recognition and rapid treatment are crucial to reduce morbidity and mortality.</div></div><div><h3>Case presentation</h3><div>Here we describe two cases of AHA in elderly female patients with no prior history of coagulopathy. The first case involved an 81-year-old woman presenting with extensive spontaneous haematomas and severe anaemia. Laboratory findings revealed an isolated prolonged activated partial thromboplastin time (aPTT), undetectable FVIII activity, and the presence of a low-titre FVIII inhibitor (2.24 BU/mL). Treatment with recombinant activated factor VII (rFVIIa) and corticosteroids led to clinical improvement and inhibitor reduction. The second case concerned an 85-year-old woman who developed severe haemorrhagic manifestations following ureteric stenting. Coagulation studies showed markedly prolonged aPTT and a high-titre FVIII inhibitor (165 BU/mL). Despite initiation of immunosuppressive therapy the patient experienced fatal complications due to uncontrolled bleeding and multi-organ failure.</div></div><div><h3>Conclusions</h3><div>These cases underscore the importance of considering a possible AHA in patients with isolated aPTT prolongation and unexplained bleeding. Punctual laboratory diagnosis, including mixing studies and FVIII inhibitor assays, is essential for early life-saving interventions. Multi-disciplinary management and rapid initiation of haemostatic and immunosuppressive therapies are key to improving outcomes in this challenging condition.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"139 ","pages":"Article 110988"},"PeriodicalIF":2.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic value of serum TSI levels in Graves’ disease and direct comparison of diagnostic performance with TRAb: A systematic review and meta-analysis 血清TSI水平对Graves病的诊断价值及其与TRAb诊断效果的直接比较：一项系统综述和荟萃分析

IF 2.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-08-09 DOI: 10.1016/j.clinbiochem.2025.110989

Ziyue Jiang , Shouxia Li , Li Yang , Xuedong Song , Xiaofang Zhang , Lili Guo , Jia Guo , Haili Zhang , Dingli Chen

This study aimed to systematically assess the diagnostic value of thyroid-stimulating immunoglobulin on the Siemens Immulite platform (the TSI assay) and to conduct a direct comparison with thyrotropin receptor antibodies on the Roche cobas platform (the TRAb assay) for the diagnosis of Graves’ disease (GD). We performed systematic literature searches across multiple databases. Following strict screening, we identified 20 eligible clinical studies that evaluated the diagnostic value of the TSI assay, either alone or in comparison with the TRAb assay. Using random-effects models, we calculated pooled estimates of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Diagnostic accuracy was further evaluated through summary receiver operating characteristic curve analysis. The findings revealed that the TSI assay demonstrated excellent diagnostic accuracy, with pooled SEN of 0.933 (95 % CI: 0.924 − 0.941), SPE of 0.961 (95 % CI: 0.956 − 0.964), PLR of 24.078 (95 % CI: 16.727 − 34.659), NLR of 0.036 (95 % CI: 0.020 − 0.066), and DOR of 778.29 (95 % CI: 343.45 − 1763.67), supported by an area under the curve (AUC) of 0.9919. In direct comparison to the TRAb assay, the TSI assay showed slightly better SEN (0.967 vs. 0.889), DOR (1310.03 vs. 692.73), and NLR (0.023 vs. 0.046), comparable SPE (0.964 vs. 0.959) and PLR (29.954 vs. 30.066), and higher AUC (0.9963 vs. 0.9899). These results conclusively demonstrate that the TSI assay shows high sensitivity and specificity in the diagnosis of GD, exceeding or at least comparable to TRAb, making it a valuable tool for clinical diagnosis.

本研究旨在系统评价促甲状腺免疫球蛋白在Siemens Immulite平台（TSI法）上的诊断价值，并与Roche cobas平台（TRAb法）上的促甲状腺激素受体抗体对Graves病（GD）的诊断价值进行直接比较。我们在多个数据库中进行了系统的文献检索。经过严格筛选，我们确定了20项符合条件的临床研究，评估TSI检测的诊断价值，无论是单独使用还是与TRAb检测进行比较。使用随机效应模型，我们计算了敏感性（SEN）、特异性（SPE）、阳性似然比（PLR）、阴性似然比（NLR）和诊断优势比（DOR）的汇总估计。通过综合受试者工作特征曲线分析进一步评价诊断准确性。结果表明，TSI法具有良好的诊断准确性，其综合SEN为0.933 (95% CI: 0.924 ~ 0.941)， SPE为0.961 (95% CI: 0.956 ~ 0.964)， PLR为24.078 (95% CI: 16.727 ~ 34.659)， NLR为0.036 (95% CI: 0.020 ~ 0.066)， DOR为778.29 (95% CI: 343.45 ~ 1763.67)，曲线下面积（AUC）为0.9919。与TRAb法直接比较，TSI法的SEN （0.967 vs. 0.889）、DOR （1310.03 vs. 692.73）、NLR （0.023 vs. 0.046）、SPE （0.964 vs. 0.959）和PLR （29.954 vs. 30.066）略好，AUC （0.9963 vs. 0.9899）更高。这些结果最终表明，TSI检测在诊断GD方面具有很高的敏感性和特异性，超过或至少与TRAb相当，使其成为临床诊断的有价值的工具。

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引用次数: 0