MAUDE data represents reports of adverse events involving medical devices. This maude entry was filed from a 04 report with the FDA on 2008-11-18 for FACTOR II (PROTHROMBIN) G20210A KIT FOR USE WITH THE LIGHTCYCLER 2.0 03610195001 manufactured by Roche Diagnostics Gmbh.
[996402]
The customer is in the process of validating the prothrombin (factor ii) g20210a kit on a new lightcycler 2. 0 instrument. Nine individual factor ii patient samples (sequence confirmed) with the 20209 mutation were tested with the factor ii test. Four of the samples generated the expected 'unknown' result and 5 of the samples yielded 'wildtype' results. All samples had the same melting temperature. On another occasion, a known factor ii 20209 heterozygous mutant sample was tested on separate days from separate sample preparations and generated one "unknown" result and one "wildtype' result.
Patient Sequence No: 1, Text Type: D, B5
[1077187]
The customer is in the process of validating the prothrombin (factor ii) g20210a kit on a new lightcycler 2. 0 instrument. Nine individual factor ii patient samples (sequence confirmed) with the 20209 mutation were tested with the factor ii test. Four of the samples generated the expected 'unknown' result sand 5 of the samples yielded 'wildtype' results. All samples had the same melting temperature. On another occasion, a known factor ii 20209 heterozygous mutant sample was tested on separate days from separate sample preparations, and generated one 'unknown' result and one 'wildype' result.
Patient Sequence No: 1, Text Type: D, B5
[8189043]
The factor ii (prothrombin) g20210a allows the detection and genotyping of a single point mutation (g to a at position 20210) of the human factor ii gene from dna isolated from human whole peripehral blood. The test is intended to be used on the lightcycler 2. 0 instrument using the lightcycler software 4. 05 or 4. 1. Within the precautions and warnings section of the package insert, under the polymorphism heading it states that mutations at positions 20207, 20209, 20218 and 20221 exist and these mutations are spanned by the mutation probe. These rare mutations will lead to an 'unknown' result after performing genotyping. Samples generating 'unknown' results are to be repeated for the entire analysis procedure including specimen preparation, amplification and detection. For the test, a 'wildype' result interpretation indicates a homozygous genotype that is negative for the factor ii (prothrombin) g20210a mutation. The kit is not designed to detect other known rare mutaiton that occur in other regions of the gene. The functional/clinical significance of these other mutations is uncertain. Some are suspected to be associated with an increased risk of thrombosis, such as the c20209t variant, although published data is inconclusive on this issue, and hence an association betwwen these rare mutations and an increased risk of thrombosis has not been proven. A 'wildtype' or 'unknown' call by the roche test could incorrectly be interpretted as meaning that the individual has no mutations elsewhere in the prothrombin gene, when in fact, in rare cases, the patient does harbor one of these other mutations. Subsequent research may eventually establish that such patients do have an increased risk of thrombosis. Patients at risk are primarily individuals who are receiving anticoagulation for a thromboembolic event and are undergoing a thrombophilia workup to determine if they have genetic risk factors for recurrent thrombosis that would influence the clinician's decision regarding the duration of anticoagulation therapy and the decision to screen other family members for thrombophilia. The degree of seriousness is difficult to gauge as the thrombotic risk associated with these variant rare mutations has not been proven. The likelihood of occurence of hazard is very low, as these other prothrombin mutations are rare existing in less than 1% of afro-americans and even lower in caucasian populations. The potential long-term consequence of this hazard would only occur if future research determines that these variant mutations carry an increased risk of thrombosis. It that were to occur, the roche test, in its current configuation, would not identify these individuals, and a clinical decision to discontinue anticoagulation could be made, when it would be more appropriate to consider indefinite anticoagulation therapy. Inappropriate discontinuance of anticoagulation in patients at increased genetic risk could result in an increased risk of new thrombotic events, which could be serious and even life threatening. Product remaining in inventory has been placed on hold until the package insert can be updated. A product advisory notice was distributed on 13 mar 2009 describing the issue and recommending users review the melting curves for wildtype results. The package insert will be revised to inform the customer there is insufficient data to know how the non-20210 mutations will be reported by the macro. Recommendations to review wildtype melting curves will also be included in the appropriate warnings and precautions sections.
Patient Sequence No: 1, Text Type: N, H10
[8227688]
Roche is in the process of trying to obtain specimen as part of the investigation. Initial analysis of the provided customer data shows that the score and resolution for the 2 replicates are very close. However, one has a slightly higher score and resolution which make it more similar to the wild type (wt) melt standard and less similar to the next closest melt standard. This may be indication that the wt result is close to the threshold of interpretation between unknown and wt. The melt standards used by the macro consist of a wt melting curve, a het melting curve and a mut melting curve. If a sample is not similar enough to one of these melt curves, and not dissimilar enough from the next closest melt curve, then it will be classified as unknown. This would explain why samples with a low score and resolution get classified as unknown. Current literature is not clear on the clinical risk associated with the 20209 mutation. Rpk 18 nov 2008 gc-0231400
Patient Sequence No: 1, Text Type: N, H10
| Report Number | 2243471-2008-00012 |
| MDR Report Key | 1233068 |
| Report Source | 04 |
| Date Received | 2008-11-18 |
| Date of Report | 2009-03-13 |
| Date Mfgr Received | 2008-10-07 |
| Date Added to Maude | 2009-03-13 |
| Event Key | 0 |
| Report Source Code | Manufacturer report |
| Manufacturer Link | Y |
| Number of Patients in Event | 0 |
| Adverse Event Flag | 3 |
| Product Problem Flag | 3 |
| Reprocessed and Reused Flag | 3 |
| Reporter Occupation | MEDICAL TECHNOLOGIST |
| Health Professional | 3 |
| Initial Report to FDA | 3 |
| Report to FDA | 0 |
| Event Location | 0 |
| Manufacturer Contact | MR. BERND SCHMIDT |
| Manufacturer Street | NONNENWALD 2 |
| Manufacturer City | PENZBERG, 82377 |
| Manufacturer Country | GM |
| Manufacturer Postal | 82377 |
| Manufacturer Phone | 8856602751 |
| Manufacturer G1 | ROCHE DIAGNOSTICS GMBH |
| Manufacturer Street | NONNENWALD 2 |
| Manufacturer City | PENZBERG, 82377 |
| Manufacturer Country | GM |
| Manufacturer Postal Code | 82377 |
| Single Use | 3 |
| Remedial Action | NO |
| Previous Use Code | 3 |
| Event Type | 3 |
| Type of Report | 3 |
| Brand Name | FACTOR II (PROTHROMBIN) G20210A KIT FOR USE WITH THE LIGHTCYCLER 2.0 |
| Generic Name | FACTOR II DNA MUTATION |
| Product Code | NPR |
| Date Received | 2008-11-18 |
| Catalog Number | 03610195001 |
| Lot Number | 14172920 |
| Device Expiration Date | 2008-09-03 |
| Operator | HEALTH PROFESSIONAL |
| Device Age | DA |
| Device Eval'ed by Mfgr | Y |
| Device Sequence No | 1 |
| Device Event Key | 0 |
| Manufacturer | ROCHE DIAGNOSTICS GMBH |
| Manufacturer Address | NONNENWALD 2 PENZBERG, 82377 GM 82377 |
| Patient Number | Treatment | Outcome | Date |
|---|---|---|---|
| 1 | 0 | 2008-11-18 |