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The binding site understands that the patient recovered renal function, and were informed on (b)(6) 2020 that the patient had been discharged from icu, and subsequently discharged from hospital.The treating physician commented that had a freelite result of 17,182 mg/l been reported to them when the sample was originally tested on (b)(6) 2019 they would have chosen an alternate course of treatment for the patient which the physician stated may have prevented their presentation with acute renal failure.Unfortunately, the sample from the (b)(6) 2019 is no longer available, and therefore cannot be tested at the binding site.However, considering the review of the customer's instrument database and the discrepancy between the initially reported freelite result and the other results available the binding site believes the sample may have been in antigen excess, which was not identified by the instrument when tested on (b)(6) 2019, but was identified when retested on (b)(6) 2020.Antigen excess is a known limitation of nephelometric and turbidimetric immunoassays, including the serum freelite assays.The spaplus analyser, as referred to (interpretation of results) of the instructions for use (ifu), has the ability to monitor reaction kinetics in order to identify samples in antigen excess.Where this occurs, it will be indicated with a p-flag associated with the result.A review of the customers database was performed to establish why the sample result obtained on (b)(6) 2019 of 150.74mg/l did not generate a p flag.Upon review of the sample reaction kinetics, it was identified that the p flag was not triggered as the calculated sample values (119.83% and 134.11%) were below the threshold values for lk018.S lot 424735 (142% and 158%).Reaction kinetics were also reviewed when this sample was repeated on (b)(6) 2020 and generated a result of 17,182mg/l, it was identified that the calculated sample values were 141.86% and 160.92%.In this instance the p flag was triggered as the calculated sample value of 160.92% exceeded the threshold values for this kit (142% and 158%).It is important to note that no automated check will identify all cases of antigen excess and a very small percentage of samples in antigen excess may not prompt the "p" flag on the spaplus freelite assay.This is referred to of the ifu where it is recommended that the following statement accompany all free light chain results."undetected antigen excess is a rare event but cannot be excluded.If the free light chain results do not agree with other clinical or laboratory findings, or if the sample is from a patient that has previously demonstrated antigen excess, the result must be checked by retesting at a higher dilution.Results should always be interpreted in conjunction with other laboratory tests and clinical evidence; any anomalies should be discussed with the testing laboratory." from the investigaton conducted to date, including review of the manufacturing records would indicate the assay antigen excess parameters were set correctly in manufacturing and this kit appears to be performing to specification.Investigations are ongoing, however, at this time we believe the sample was in antigen excess, which was not identified by the instrument when tested on (b)(6) 2019 but was identified when retested on (b)(6) 2020.Following the initial report from the healthcare facility the binding site discussed this case with a consultant haemotologist.They commented that to catch a patient at this point would be very unusual (a single event in thousands of cases).For a patient to present with such high flc and no direct evidence of renal impairment and then within weeks require dialysis would mean that the patient had a very aggressive tumour, but the sample was taken before any renal symptoms had occurred.The patient was still treated for their myeloma, and the consultant haemotologist stated that there is no objective available evidence that an alternative treatment would have a higher likelihood of preventing renal failure.At this point in time this adverse event has been classified as a user error by the binding site uk as the lambda free light chain result in question was contradictory to other available test results.These test results (specifically the incongruous spe and upe lambda free light chain results) were available to both the laboratory and the treating physician.When following the product instructions for use the incongruous results from spe and upe would have indicated a check for antigen excess by the laboratory by retesting at a higher dilution.
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This event did not occur in the usa.We are submitting this report as the event occured at a healthcare facility in (b)(6) on a device that is also marketed in the usa.The resulting complaint and investigation were coordinated between the binding site (b)(6), the manufacturer of the device, and the binding site (b)(6), the sponsor of the device in (b)(6).On (b)(6) 2019 a patient sample was tested using the binding site's freelite lambda free kit for use on the spaplus, at a healthcare facility in (b)(6).This gave a final free lambda result of 151 mg/l (95 percentile reference interval: 5.71 - 26.30 mg/l), with no antigen excess check flag.This result was subsequently reported to the physician.The patient was treated for their myeloma.The patient developed acute renal failure and was admitted to the icu on (b)(6) 2020, and placed on dialysis.A new sample was tested on (b)(6) 2020 which gave a result of 27,454 mg/l.Subsequently the sample which was tested and retained on (b)(6) 2019 was thawed and retested, and a final result of 17,182 mg/l obtained.The treating physician commented that had a freelite result of 17,182 mg/l been reported to them when the sample was originally tested on (b)(6) 2019, they would have chosen an alternate course of treatment for the patient which the physician stated may have prevented their presentation with acute renal failure.The binding site's review of the customer's instrument database indicated that when the patient sample was tested on (b)(6) 2019 this did not prompt a prozone flag as the sample results were below the minimum parameter limits for this kit.When the serum lambda free light chain result of 151 mg/l was reported on (b)(6) 2019 there were a number of other patient results available including: serum electrophoresis (epg) (free lambda = 4 g/l; igg lambda = 34 g/l), urine electrophoresis (upe) (free lambda = 3.2 g/l) which were inconsistent with the serum free light chain result.We also understand that egfr and creatinine were 56 ml/min/1.73m2 and 88 umol/l respectively.When the sample from the (b)(6) 2019 was retested on (b)(6) 2020 the initial result reported at the standard dilution was >157 mg/l and reflexed to subsequent dilutions and a final result of 17,182 mg/l including a prozone flag was returned.The binding site therefore believes it is most likely that the sample was in antigen excess.
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