TINA-QUANT ALBUMIN GEN.2

Additional Manufacturer Narrative

THE C503 ANALYZER SERIAL NUMBER WAS (B)(6). IT WAS NOTED THAT THE SAMPLES WERE COLLECTED, FROZEN AT -80 °C, DEFROSTED, CENTRIFUGED, AND THE SUPERNATANT SEPARATED IN A DIFFERENT LABORATORY, THEN SENT TO THE CUSTOMER SITE. THE CUSTOMER DID NOT RE-CENTRIFUGE THE SAMPLES PRIOR TO RUNNING ON THE C503 ANALYZER. THE INVESTIGATION IS ONGOING.

Description of Event or Problem

THE INITIAL REPORTER QUESTIONED HIGH RESULTS NOT CORRESPONDING TO THE CLINICAL CONDITION FOR MULTIPLE PATIENT SPONTANEOUS URINE SAMPLES TESTED FOR TINA-QUANT ALBUMIN GEN.2 (ALBT2) ON A COBAS C 503 ANALYTICAL UNIT. THE CUSTOMER IS QUESTIONING THE ALBT2 RESULTS AS THEY ARE ALLEGEDLY "MUCH HIGHER" THAN THE TOTAL PROTEIN RESULTS. ALL OF THE AFFECTED PATIENTS ARE TAKING ACE INHIBITORS. THE CUSTOMER ALLEGES THE ISSUE ONLY AFFECTS PATIENTS TAKING ACE INHIBITORS. THE FOLLOWING ARE EXAMPLES OF RESULTS FOR 3 PATIENT SAMPLES. PATIENT 1 ALBT2 RESULT WAS 1263 MG/L. THE TOTAL PROTEIN RESULT WAS 1133 MG/L. PATIENT 2 ALBT2 RESULT WAS 1015 MG/L. THE TOTAL PROTEIN RESULT WAS 765 MG/L. PATIENT 3 ALBT2 RESULT WAS 1388 MG/L. THE TOTAL PROTEIN RESULT WAS 1072 MG/L. SERUM CARRYOVER WAS SUSPECTED, AND THE CUSTOMER PERFORMED A TEST WITH URINE SAMPLES. FOR THESE SAMPLES, THE INITIAL RESULTS WERE ACCOMPANIED BY DATA FLAGS; THE REPEAT RESULTS WITH DILUTION WERE LOWER. THE FOLLOWING IS AN EXAMPLE FROM THIS TEST: THE INITIAL ALBT2 RESULT WAS 551 MG/L WITH AN INVALIDATING DATA FLAG. THE REPEAT WITH DILUTION WAS 432 MG/L THE TOTAL PROTEIN RESULT WAS 389 MG/L THE CUSTOMER HAS BEEN PERFORMING URINE ALBUMIN AND URINE TOTAL PROTEIN TESTING ON ALL PATIENT SAMPLES RECEIVED BY THE LABORATORY, AND THE ISSUE WAS NOT OBSERVED FOR THESE SAMPLES.

Additional Manufacturer Narrative

A GENERAL REAGENT ISSUE WAS EXCLUDED AS CALIBRATION, AND QC WERE ACCEPTABLE. INSTRUMENT FILES SHOWED SAMPLE ASPIRATION AND CELL BLANK ALARMS; THESE ALARMS SUGGEST PREANALYTICAL HANDLING ISSUES. THE FIELD SERVICE ENGINEER (FSE) CHECKED THE WATER SUPPLY PUMP PRESSURE, THE VACUUM PRESSURE, AND THE CELL RINSE UNIT. THE CUSTOMER ALLEGED THE ISSUE ONLY AFFECTED PATIENTS TAKING ACE INHIBITORS. ACE INHIBITORS REDUCE HIGH-MOLECULAR-WEIGHT PROTEIN LEAKAGE, CREATING A URINE MATRIX COMPRISED ALMOST ENTIRELY OF ALBUMIN. IT WAS NOTED THAT THE SAMPLES HAD BEEN FROZEN AT -80 °C AND MEASURED WITHOUT IMMEDIATE RE-CENTRIFUGATION. ALBUMIN MOLECULES IN THIS SPECIFIC MATRIX ARE PRONE TO SELF-AGGREGATION AFTER FREEZE-THAW CYCLES (AT -80 °C). THE ALBT2 ASSAY (IMMUNOTURBIDIMETRIC) IS SENSITIVE TO THESE AGGREGATES AND MAY LEAD TO A FALSELY ELEVATED SIGNAL. IN CONTRAST, THE TOTAL PROTEIN ASSAY (NON-IMMUNE TURBIDIMETRIC) MAY NOT FULLY PRECIPITATE THESE AGGREGATED PROTEINS, RESULTING IN A LOWER RECOVERY COMPARED TO THE ALBT2 ASSAY. THE ALBT2 IMMUNOTURBIDIMETRIC METHOD IS GENERALLY MORE SPECIFIC THAN THE TOTAL PROTEIN TURBIDIMETRIC METHOD. THE ISSUE ONLY OCCURRED FOR SAMPLES WITH HIGH ANALYTE CONCENTRATIONS. FROZEN SAMPLES SHOULD BE CENTRIFUGED IMMEDIATELY BEFORE TESTING WITH AUTOMATED DILUTIONS. BASED ON THE INFORMATION PROVIDED, THE SPECIFIC CAUSE OF THE EVENT COULD NOT BE DETERMINED.