Citations

Abstract Background The Freelite serum free light chain (FLC) assay has been widely used for detecting and monitoring monoclonal gammopathies. Reference intervals (RIs) established by Katzmann et al. in 2002 have served as the standard values for interpreting kappa/lambda FLC ratios. However, multiple reports suggested an assay drift and clinical laboratories started to move towards locally established RIs given the challenge in verifying original RIs. The assay drift over time increased kappa concentration measurements and was attributed to an interaction between the kappa FLC calibrator and serum proteins, including alpha-1-antitrypsin. A stabilized calibrator was developed to improve consistency of results with original RI. The objective of this study was to assess whether the new updated kappa calibrator would warrant a RI update. Methods Healthy adult donors’ serum samples were selected from the institution quality unit. Exclusion criteria included autoimmune diseases, cancers and renal disease. FLC measurements were obtained on the Optilite by turbidimetry using routine reagents for kappa (old lot); the new lot of reformulated kappa calibrator, and a single measurement for lambda FLC. FLC ratios were calculated with the old lot and new lot. All samples were tested by MASS-FIX to confirm absence of a monoclonal protein. Bootstrap resampling (10,000 replicates) estimated standard errors, with statistical significance defined as p < 0.05. Clinical significance was assessed per CLSI EP28-A3 guidelines. A RI was considered for partitioning by sex if the mean difference between males and females exceeded 25% of the RI width or if >4% of either sex had values beyond RI limits. Similar tests were applied to age groups (<60 and =60 years). Results 465 donors (48.2% male, 51.8% female) aged 30-89 years were used. Sixteen donors with incidental monoclonal proteins identified by MASS-FIX were excluded, for a final n=449. No clinically significant relationships of results were found with sex or age. The updated kappa calibrator resulted in a measurable shift down in FLC values with the new lot of reagents. The kappa FLC concentration and corresponding FLC ratio decreased by a median -12.1%, see table 1 for absolute values When reviewing Optilite results of the new lot, 98/449 samples were outside the kappa concentration original RI (21%). Lambda concentration RI was shifted up on Optilite when compared to original RI but passes verification (1.6% of samples, acceptance criteria < or =10%). 19 samples (4.2%) were outside the original RI for the FLC ratio of 0.26 to 1.65 (all >1.65), which was originally established as a 100% diagnostic range. The calibrator reformulation, while decreasing test results by >10%, was not sufficient to verify the original RI for kappa and still left a few cases outside the original diagnostic range for the FLC ratio. Conclusion This study assessed the impact of the stabilized calibrator on RIs for the Optilite Freelite assay. These findings suggest revisiting existing RIs to ensure continued accuracy in clinical interpretation and should be further evaluated with additional lots of reagents for robustness.

Abstract Background Cryoglobulins are immunoglobulins that precipitate at cold temperatures. They are associated with plasma cell disorders, infectious and autoimmune diseases. Laboratory testing is manual and requires strict temperature control, from keeping the blood sample warm from the moment of draw until processing in the laboratory. Serum samples are transferred to Kolmer glass graduated tubes upon arrival, and kept on ice for visualization of a precipitate for up to 7 days. Because of the temperature variation samples are subjected to, positive sample identification is important. The Kolmer glass tubes are not disposable, and undergo several steps of deidentification and cleaning for reuse. The goal of this project was to improve patient safety and label adherence in cryoglobulin testing by using the Managing for Daily Improvement (MDI) method to monitor and implement changes effectively. Methods During a Plan Do Study Act (PDSA) initiative, it was discovered that labels were not being secured on both ends with tape due to safety concerns when using a box cutter to remove the label prior to cleaning. This practice led to an increase in labels detaching from the glass tubes. To address this issue, we employed the MDI method and established a Key Performance Indicator (KPI) to monitor and evaluate potential changes aimed at improving label adherence. The MDI method facilitates problem-solving through daily visual indicators and discussions by empowering technologists to identify and address issues affecting daily operations. This approach encourages open communication and collaborative problem-solving, allowing the entire team to share insights and solutions in real time. Results A PDSA initiative via MDI uncovered the label adherence challenges. A KPI was developed to monitor interventions to improve the process. First, removable tape was used to secure both sides of the label. Initial results were worse than the original method but slight improvement occurred at about 3 weeks. A Just Do It (JDI) approach was initiated to leave additional space between samples. No improvements were observed and the practice discontinued within < 2 weeks. A second JDI was trialed with a different tool to remove labels post-use. The entire sample identification process was reviewed and the original identification process resumed, by adding scotch tape securing both sides of the labels and using a ceramic box cutter to remove the labels. Significant improvements to labels adherence was observed, from about 60% of labels coming off to zero, while the new tool was also safer for the team. Another PDSA was initiated to investigate if plastic, disposable tubes were a viable option for testing, and a full method validation of the new plastic tubes followed, finally eliminating the challenges with the larger process or reusing glass tubes. Conclusion MDI helped recognize a problem from the front-line and find real time solutions that benefited end-to-end operations. Visual daily indicators clearly showed effectiveness of interventions. Identifying real issues, even if they appear small, can lead to improved patient and staff safety, and empowerment to initiate meaningful change.