Background
It is critical for laboratories to conduct multianalyzer comparisons as a part of daily routine work to strengthen the quality management of test systems. Here, we explored the application of patient‐based real‐time quality controls (PBRTQCs) on comparative assays to monitor the consistency among clinical laboratories.
Methods
The present study included 11 commonly tested analytes that were detected using three analyzers. PBRTQC procedures were set up with exponentially weighted moving average (EWMA) algorithms and evaluated using the AI‐MA artificial intelligence platform. Comparative assays were carried out on serum samples, and patient data were collected. Patients were divided into total patient (TP), inpatient (IP), and outpatient (OP) groups.
Results
Optimal PBRTQC protocols were evaluated and selected with appropriate truncation limits and smoothing factors. Generally, similar comparative assay performance was achieved using both the EWMA and median methods. Good consistency between the results from patients' data and serum samples was obtained, and unacceptable bias was detected for alkaline phosphatase (ALP) and gamma‐glutamyl transferase (GGT) when using analyzer C. Categorizing patients' data and applying specific groups for comparative assays could significantly improve the performance of PBRTQCs. When monitoring the inter‐ and intraanalyzer stability on a daily basis, EWMA was superior in detecting very small quality‐related changes with lower false‐positive alarms.
Conclusions
We found that PBRTQCs have the potential to efficiently assess multianalyzer comparability. Laboratories should be aware of population variations concerning both analytes and analyzers to build more suitable PBRTQC protocols.
Factor X (FX) is a vitamin K-dependent plasma zymogen, which following activation to factor Xa (FXa), converts prothrombin to thrombin in the blood clotting cascade. It was recently demonstrated that a natural variant of FX carrying the Asp-185 deletion (FX-D185del, chymotrypsinogen numbering) was associated with mild bleeding in a patient with severe FX deficiency. In this study, we expressed FX-D185del in mammalian cells and characterized its properties in appropriate kinetic assays in purified systems. We discovered that while the FX variant can be normally activated by physiological activators; both amidolytic and proteolytic activities of the mutant are dramatically impaired. Interestingly, factor Va (FVa) significantly improved the proteolytic defect when the mutant protease was assembled into the prothrombinase complex. Thus, in contrast to >50-fold catalytic defect in the absence of FVa, the variant activated prothrombin with only ~2.5-fold decreased catalytic efficiency in the presence of the cofactor. The FXa variant dramatically lost its susceptibility to inhibition by antithrombin and tissue factor pathway inhibitor, thus exhibiting ~2–3 orders of magnitude lower reactivity with the plasma inhibitors. Further studies revealed that Na+ no longer activates the variant protease, suggesting that the functionally important allosteric linkage between the Na+-binding and the P1-binding sites of the protease has been eliminated. These results suggest that the lower catalytic efficiency of FXa-D185del in the bleeding patient may be partially compensated by the loss of its reactivity with plasma inhibitors, possibly explaining the basis for the paradoxical severe FX deficiency with only mild bleeding tendency for this mutation.
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