Annals of Clinical Biochemistry最新文献

Strict homoeostatic control of potassium is necessary for normal muscle and neural function, and as a result, hyperkalaemia can be life-threatening and requires timely management. Prior to treating the patient, however, it is important to determine if hyperkalaemic blood test results are authentic and not due to pre-analytical factors as treatment in this context may provoke potentially dangerous hypokalaemia. We present the case of a 47-year-old female referred for further investigation following 2 years of otherwise unexplained intermittent hyperkalaemia. Her highest recorded potassium was 8.9 mmol/L (reference interval: 3.5-5.2 mmol/L). She was otherwise healthy, not on regular medications, and asymptomatic during these episodes. There was no evidence of associated electrocardiogram (ECG) changes. She had been referred to the Emergency Department twice in 6 months due to hyperkalaemia, but these episodes resolved on repeat testing without any intervention. Further investigation revealed a significant time- and temperature-dependent increase in potassium concentration in whole blood samples, compared to a control. ABCB6 single gene testing revealed a heterozygous variant, c.1123 C>T, p. (Arg375Trp), consistent with a diagnosis of familial pseudohyperkalaemia (FP). This is an autosomal dominant condition, which results in increased efflux of potassium from red blood cells at sub-physiological temperatures. Whilst this is an ex vivo phenomenon, unless recognised it poses a clinical risk to patients as they may be treated erroneously.

Background: The rise in serum thyroid stimulating hormone (TSH) in healthy older adults is well established. However, age-related reference intervals are not widely used. We aimed to establish all-adult and age-related reference intervals for TSH, free thyroxine (FT4) and free triiodothyronine (FT3) and determine their impact on primary care thyroid testing results.

Methods: We measured TSH, FT4 and FT3 by Roche Cobas assays in a reference cohort of 1364 anti-thyroid peroxidase antibody negative adults with no self-reported medical conditions or medications. Reference intervals were generated for all-adult, 18-60 and over 60-years. Reference intervals were applied to 21,286 primary care tests with no known thyroid disease to assess effect on test interpretation.

Results: In the reference cohort, 23.2% were over 60 years compared to 50.4% of those undergoing thyroid testing in primary care. With an all-adult reference interval, 8.2% of over 60s had an elevated TSH, 7.0% were classified as subclinical hypothyroid and 0.8% as overt hypothyroid. With age-related reference intervals, this fell to 4.4% with an elevated TSH, 3.7% subclinical hypothyroid and 0.4% overt hypothyroid. Minimal changes were seen in the 18-60 years group.

Conclusions: An all-adult reference interval derived from healthy and therefore younger individuals is less appropriate for the older subset of the population being tested. Application of an age-related reference interval for over 60s would reduce the proportion of patients with abnormal thyroid test results. In turn, this would decrease potentially unnecessary cascade and repeat testing as well as regular follow-up in primary care.

Background: Serum copper is an essential trace element, and accurate quantification is important for assessing copper status in pregnancy. Current serum copper assays are limited by inaccuracy, poor inter-method comparability, and difficulties in transferring reference intervals (RIs) between populations. This study aimed to establish an inductively coupled plasma mass spectrometry (ICP-MS)-based candidate reference method for serum copper and to verify whether multicenter RIs for serum copper can be transferred to a Chinese population.

Methods: Cobalt was used as the internal standard. After nitration with ultrapure nitric acid, samples were diluted 100-fold with ultrapure water. The ⁶³Cu/⁵⁹Co ratio was measured in helium collision mode at a gas flow rate of 5 mL/min. Analytical performance was validated, and serum copper RIs in pregnant and non-pregnant women were subsequently verified.

Results: The candidate reference method demonstrated excellent linearity, with a correlation coefficient (R) >0.99998 over 0-13.75 μg/g. Total precision ranged from 0.30% to 0.40%, and spike recovery was 100.06% (99.95-100.14%). Trueness was confirmed by measurements of NIST SRM 1598a within the certified value and stated uncertainty. The RI for healthy non-pregnant women was transferable to healthy Chinese women, whereas the pregnancy-specific RI was not fully transferable.

Conclusion: A highly sensitive and specific candidate reference method for serum copper was established, strengthening the reference measurement system and contributing to the standardization and harmonization of serum copper assays. Pregnancy-specific RIs for serum copper in Chinese women should be established.

Background: Laboratory test results are crucial for clinical decisions, but errors at any stage can compromise patient safety. Despite technological advances and quality systems, laboratory processes remain vulnerable, necessitating structured risk assessment. Limited research exists on integrating Failure Mode and Effects Analysis (FMEA) with Sigma metrics. This study addresses these gaps through a comprehensive risk assessment in a NABL-accredited tertiary care hospital laboratory.

Methods: A retrospective observational study was conducted over 2.5 years. FMEA was used to identify errors across all phases of the total testing process. Quarterly error rates were calculated, converted to defects per million (DPM), and expressed as Sigma metrics. Risk Priority Numbers (RPN = severity × detectability × frequency) were scored quarterly to prioritize failures. The effect of corrective actions was evaluated by comparing pre- and post-intervention Sigma values.

Results: Across ten quarters (five pre- and five post-intervention), 23 error types were identified. The highest RPNs (>20) were observed for haemolysed samples, clotted samples, and non-intimation of critical values. Haemolysed samples declined from 0.97% to 0.49% (ARR 0.48%; RR 0.51; 95% CI 0.47-0.55; p < 0.0001). Clotted samples reduced from 0.24% to 0.06% (ARR 0.18%; RR 0.24; 95% CI 0.20-0.29; p < 0.0001). Non-intimation of critical values decreased from 2.63% to 2.18% (RR 0.83; 95% CI 0.70-0.99; p = 0.065).

Conclusion: Integrating FMEA with Sigma metrics provides a robust framework for identifying, prioritizing, and reducing laboratory errors. Continuous monitoring and corrective action are essential to sustain improvements in laboratory quality and patient safety.

Background: Conventional transcutaneous bilirubinometers often underestimate total bilirubin (TB) levels at high concentrations, limiting their clinical utility in cases of neonatal hyperbilirubinemia. We aimed to address this shortcoming by developing and testing a novel type of advanced transcutaneous bilirubinometer that may enhance the early identification of severe hyperbilirubinemia, potentially reducing the need for invasive testing and exchange transfusions.

Methods: We developed a novel transcutaneous bilirubinometer with adjustable light intensity and detection distances. Transcutaneous bilirubin (TcB) measurements were obtained using both the novel device and a conventional JM-105 bilirubinometer in 66 instances in 62 neonates (≥36 weeks gestation). TB values measured in patient blood samples were used as reference values for calculating correlations and error metrics (i.e., mean squared error [MSE] and mean absolute error [MAE]).

Results: The novel device showed strong correlation with TB values across all concentrations (R² = 0.96), including those ≥15 mg/dL (R² = 0.84), outperforming the JM-105 device (R² = 0.60 for TBs ≥15 mg/dL). The novel device also yielded lower MSE (1.53 vs. 2.95) and MAE values (1.00 vs. 1.39) than the JM-105.

Conclusions: Our novel transcutaneous bilirubinometer demonstrated improved accuracy at higher bilirubin concentrations compared with a conventional JM-105 device.

Objectives To evaluate the stability of commonly used biomarkers in whole blood under various storage conditions, in order to assess their suitability for home-based blood collection in remote care settings. Methods Whole blood samples were stored at 4-8 °C, 20-25 °C, and 37 °C for up to 72 hours. Six pooled samples and two healthy volunteer samples were aliquoted and analysed at four time points (T0, T24, T48, T72 hours). A panel of 47 routine chemistry and immunochemistry biomarkers was measured in all samples. Recoveries relative to T0 were compared to within subject coefficients of variation of the individual biomarkers. Results Most biomarkers remained stable at refrigerated and room temperature conditions up to 72 hours with a subset of biomarkers, mostly proteins and tumour markers also showing good to acceptable stability at 37 °C. Several biomarkers, including potassium, inorganic phosphate and iron, consistently fell outside acceptable limits under multiple conditions. Others, such as sodium, calcium, ferritin, aspartate aminotransferase and cytokeratin fragment 21-1, were unstable only at 37 °C . A few transient deviations were observed but these were not consistent over time. Conclusions Home-based blood sampling is feasible for a broad range of biomarkers, provided that heat exposure during transport is minimised. These findings are a first step in the further validation of selected analytes under real-world, capillary blood sampling conditions.

BackgroundTocilizumab co-administration and inflammatory conditions potentially alter the activity of cytochrome P450 (CYP) 3A4 by modulating the interleukin-6 (IL-6) signaling pathway in patients with rheumatoid arthritis (RA). This study aimed to evaluate the correlations of serum levels of tocilizumab with IL-6 and CYP3A activity in RA.MethodsRA patients (n = 35) with controllable disease activity using intravenous or subcutaneous tocilizumab were enrolled. Serum tocilizumab was monitored at the trough point after reaching steady-state. Serum levels of IL-6, its soluble receptor (sIL-6R), 4β-hydroxycholesterol (4β-OHC), and 25-hydroxyvitamin D (25-OHD) and CYP3A5 genotype were determined.ResultsThe RA patients had a wide variation of serum tocilizumab level (interquartile range, 9.8-24.6 µg/mL). Tocilizumab treatment led to abnormally high levels of serum IL-6 and sIL-6R. The serum level of tocilizumab was correlated with that of IL-6 but not sIL-6R. In the tocilizumab-treated RA patients, the median serum levels of 4β-OHC and 25-OHD were 36.7 and 17.7 ng/mL, respectively, and no correlations with the serum level of tocilizumab were observed. CYP3A5 genetic polymorphisms were not also associated with the serum level of 4β-OHC. RA patients with the CYP3A5*1 allele exhibited a correlation between serum levels of tocilizumab and 4β-OHC, while those with CYP3A5*3/*3 did not.ConclusionsTocilizumab treatment raised the serum IL-6 level in a concentration-dependent manner. In the RA patients with functional CYP3A5 protein, the serum tocilizumab level partially explained the interindividual variation in CYP3A activity.