[20939716]
This problem has been reported in a published manuscript - false - negative results in point-of-care qualitative human chorionic gonadotropin - hcg- devices due to excess hcg? Core fragment clin. Chem. , jul 2009; 55: 1389 - 1394, abstract copied below. We have also written a follow-up letter to the editor indicating that we have also seen this problem using the combo device by cardinal health. I've copied part of that manuscript below as well. Background: during pregnancy, hcg immunoreactivity in urine consists of intact hcg as well as a number of hcg variants including the core fragment of hcg? - hcg -cf. We identified three urine specimens with apparent false negative results using the osom hcg combo test - genzyme diagnostics - qualitative hcg device and sought to determine whether an excess of one of the fragments or variants might be the cause of the interference. Methods: concentration of hcg variants were determined in the urine from the three pts with apparent false negative hcg results. Purified hcg variants were added to urines positive for hcg and tested using the osom, icon 25 hcg -beckman coulter-, and hcg combo sp brand - cardinal health- devices. Results: dilution of these three urine samples resulted in positive results on the osom device. Quantification of hcg variants in each of the three pt urine specimens demonstrated that hcg? Cf of occurred in molar excess of intact hcg. Addition of purified hcg? Cf to hcg-positive urines caused false negative hcg results using the osom and icon qualitative urine hcg devices. Conclusions: elevated concentrations of hcg-cf can cause false negative results on the osom and icon qualitative urine hcg devices. Manuscript submitted to clinical chemistry dear editor: recently, we reported that elevated concentrations of hcg? Cf can cause false negative results on the osom hcg combo test - genzyme diagnostics - and icon 25 hcg - beckman coulter - qualitative urine hcg devices - 1 -. We reported that the combo sp brand - cardinal health - device, however, was not subject to the same effect. Here we demonstrate that the false negative effect is visible in certain lots of the combo sp devices. Approximately nine months after our hospital system switch to the combo device to avoid potential false negative results observed in pts with high concentrations of urine hcg -cf, we encountered two pts with false negative results. Pt 1 with a live intrauterine pregnancy seen on ultrasound estimated at 12 weeks gestation. She presented to the emergency department - ed - with abdominal pain - no bleeding. Her discharge diagnosis was hyperemesis gravidarum and dehydration. Urine was cloudy with a ph 6. 5, specific gravity 1. 026 and 1+ leukocyte esterase. A point-of-care -poc - urine pregnancy test was performed in the ed - combo; lot# 9020102 - and was negative. A second urine specimen was collected and was also negative. Serum hcg was 166, 659 iu/l using the siemens centaur total hcg assay. The urine specimens were also quantified on the seimens centaur and were 173,949 iu/l and 155,625 iu/l respectively. Dilution of both specimens at 1:10 and 1:100 gave clearly positive results on the combo sp device. These specimens were tested using the osom and icon devices and were also negative as previously seen -1 -. Pt 2 who presented to the ed with abdominal pain. She had a live intrauterine pregnancy and an estimated gestational age of 15 weeks. Her urine was cloudy with a ph 7. 0, specific gravity 1. 021 and 3+ leukocyte esterase. The combo sp device - lot# 9020102 - produced a negative result in the ed. Serum hcg was 157, 681 iu/l and urine hcg was 186, 977 iu/l using the centaur total hcg assay. Urine hcg variant composition from both pts was determined by a combination of commercial and in-house immunofluorometric assays -ifma -as described -1-. The urine hcg? Of concentration was 2,130,000 pmol/l - 67% of total immunoreactive hcg - in pt 1 and 1,097,00 pmol/l - 58% of total immunoreactive hcg - in pt 2. These hcg - cf concentrations and percent of total immunoreactive hcg were similar to those that demonstrated false negatives with the osom and icon devices -1-, suggesting that hcg? - cf might also be the cause of the false negative effect seen here. To investigate this possibility, we repeated our original inhibition studies using purified hcg? Cf purchased from the national institute for biological standards and controls - hertfordshire, uk - [1st who reference reagent, 2001 - hcg - cf, 99/708 - ]. Hcg - cf was diluted in hcg-negative urine to a concentration of 3000 nmol/l. A randomly chosen positive urine specimen was mixed with purified hcg? Cf at concentrations from 62. 5 nmol/l to 1,000 nmol/l and tested using two different lots of the combo device - lot# 8080021 and lot# 9020102-. The results clearly demonstrate a lot-to-lot difference in the effect of hcg cf on the results from hcg positive urine - figure 1-. Lot# 8080021 was unaffected by up to 1000 nmol/l hcg? Cf, whereas lot# 9020102 was inhibited in a dose-dependent manner by hcg-cf and at a concentration of 1000 nmol/l was nearly invisible figure 1-. These data clearly demonstrate the same inhibition by hcg? Cf, in one lot of the combo device, that was previously reported for the osom and icon devices. It is unclear why these devices exhibit such between-lot variation. The package insert states that the device utilizes one monoclonal antibody and one polyclonal antibody. It is possible that a new batch of polyclonal antibody was used that possessed more avid specificity for hcg? Cf or it was used at a concentration giving lower binding capacity for hcg. These data suggest that extreme caution needs to be used when interpreting any negative result from any device. At this point in time, we have not found a device that is free from the inhibition effect by hcg? Cf. This observation has been reported to the manufacturer and the fda.
Patient Sequence No: 1, Text Type: D, B5