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False positives in transfusion-transmitted infection proficiency testing due to matrix effects in external quality
Rasika Dhawan Setia1, Mitu Dogra1, Gajendra Gupta2
1Department of Transfusion Medicine, BLK-Max Super Speciality Hospital, New Delhi, India.
Introduction:
Proficiency testing, a cornerstone of external quality assessment, benchmarks laboratory performance and detects systematic errors. Although extremely rare, matrix-related interference in proficiency testing samples can produce misleading results across platforms, highlighting the importance of sample commutability.
Methods:
During a proficiency testing cycle for transfusion-transmitted infections, a blood center observed uniform low hepatitis B surface antigen reactivity in 5 blinded samples on the Alinity i chemiluminescent microparticle immunoassay (CMIA) platform (Abbott). This consistent yet unusual reactivity prompted further investigation. Cross-validation using the Roche Elecsys-e411 analyzer, Abbott ARCHITECT i1000SR analyzer, and the bioMérieux VIDAS enzyme-linked fluorescent assay (ELFA) showed similar results, whereas the QuidelOrtho VITROS 3600 chemiluminescence immunoassay reported 4 nonreactive results and 1 invalid result. Reflex testing on rapid immunochromatographic tests, nucleic acid testing (NAT), and neutralization assays was performed. A reflex testing protocol that integrated orthogonal methodologies, root cause analysis, and corrective maintenance were employed to systematically investigate discordance.
Results:
The CMIA consistently showed low reactivity; the ELFA was borderline; and the VITROS 3600, rapid tests, and NAT were nonreactive. Neutralization assays confirmed nonspecific signals. Instrument issues were excluded. The external quality assessment provider attributed these findings to matrix interference, likely from stabilizers. Performance assessment used a peer group methodology.
Discussion:
Matrix interference in proficiency testing, although rare, can compromise interpretation. Reflex testing, structured root cause analysis, robust standard operating procedures, staff training, and attention to sample commutability are essential to strengthen quality assurance.
Insights
Matrix interference in proficiency testing (PT) can cause misleading results, impacting laboratory performance. Investigating discordant PT results using orthogonal methods and root cause analysis is crucial for accurate quality assessment.
Area of Science:
- Clinical diagnostics
- Laboratory medicine
- Quality assurance
Background:
- Proficiency testing (PT) is vital for laboratory performance benchmarking and systematic error detection.
- Matrix interference in PT samples, though rare, can lead to erroneous results and underscores the need for sample commutability.
Purpose of the Study:
- To investigate unusual low hepatitis B surface antigen reactivity observed during a transfusion-transmitted infections proficiency testing cycle.
- To identify the root cause of discordant results across multiple immunoassay platforms.
Main Methods:
- Observed uniform low reactivity on the Alinity i chemiluminescent microparticle immunoassay (CMIA) platform.
- Performed cross-validation using Roche Elecsys-e411, Abbott ARCHITECT i1000SR, bioMérieux VIDAS enzyme-linked fluorescent assay (ELFA), and QuidelOrtho VITROS 3600.
- Employed reflex testing with rapid tests, nucleic acid testing (NAT), neutralization assays, root cause analysis, and corrective maintenance.
Main Results:
- CMIA showed low reactivity, ELFA was borderline, while VITROS 3600, rapid tests, and NAT were nonreactive.
- Neutralization assays confirmed nonspecific signals, ruling out instrument issues.
- External quality assessment provider identified matrix interference, likely from stabilizers, as the cause.
Conclusions:
- Matrix interference in PT can compromise result interpretation, emphasizing the importance of sample commutability.
- Reflex testing, root cause analysis, and robust standard operating procedures are essential for strengthening laboratory quality assurance.
