Quality control of CoaguChek test strips in the Netherlands

Thromb Haemost 2007; 97: 323–324 Dear Sir, Point-of-care systems have been developed for INR testing using capillary blood samples. One of the principal point-of-care systems, the CoaguChek-S (Roche Diagnostics, Mannheim, Germany) is widely used in the Netherlands. The Federation of Dutch Thrombosis Services set up a system for the training of personnel and patients using point-of-care INR monitors. In addition, guidelines were given by the Federation for quality control of the point-of-care systems used by professionals and patients. In a recent paper we showed that deep-frozen pooled plasma can be used for long-term stability monitoring of CoaguChek-S test strips (1). It was shown that there were statistically significant INR differences between strip lots when testing was performed with recalcified plasmas. Since the CoaguChek-S system was designed for whole blood testing and the strip lots were calibrated with whole blood samples, identical INR results may not be expected when different strip lots are used with recalcified plasma. In another study, significant inter-lot differences of performance were found for lyophilized artificially depleted plasmas (2). Here we report the first results of quality control of consecutive lots of CoaguChek-PT test strips introduced in the Netherlands, using whole blood samples. One lot of test strips was used as master lot (number 965) with which the other lots were compared. First of all the master lot was compared to the international standard rTF/95, as described previously (3). Each new lot was sent together with the master lot to three thrombosis centers in the Netherlands. Each center tested the new lot and the master lot with capillary blood samples from eight patients on long-term oral anticoagulant therapy. The combined results from the three centers were used to assess the differences between the new lot and the master lot. For each new lot, a different set of 24 patient samples were used. The mean INRs calculated for each lot are shown in Table 1. Differences were tested with a t-test on paired observations. Two strip lots showed a significant difference with the master lot. The mean INR differences between the master lot and the other test lots assessed with fresh blood samples were not greater than 6.2%. The mean INR differences between the test lots can be calculated by subtracting the mean differences relative to the master lot. The largest mean difference was observed for lot 019 when compared to lot 085: +6.2 –(-3.6) = 9.8%. For individual patients, differences in INR between test lots and the master lot were observed, and the ranges are shown in Table 1. For one patient, an INR of 3.1 was obtained with test lot 139 and an INR of 2.4 with the master lot. The operator reported that the pouch of the strip used for this patient was damaged in the mail. It cannot be excluded that the difference in INR might be due to the damage. Apart from this patient’s results, the individual differences were not greater than 21%. It should be noted that only single measurements were made for each patient and each strip lot. The imprecision coefficient of variation of a single measurement on capillary blood in the CoaguChek has been reported as 4.7% (4) and 5.5% (5). Part of the differences in INR between the strip lots were caused by imprecision of the measurement. In our previous study we used deep-frozen pooled coumarin plasmas for long-term stability monitoring of CoaguChek test strips (1). The plasmas were recalcified immediately before application to the test strip. In addition to testing of capillary blood samples, three deepfrozen pooled plasmas were assayed on the same CoaguChek strip lots by our center. The deep-frozen plasmas were analyzed with each strip lot on different occasions. The mean difference between lot 019 and the master lot was +6.2% for fresh blood samples, and was 5.0 – 7.4% for plasma samples.This was indeed in good agreement. However, the interlot differences observed with capillary blood samples did not always agree with the inter-lot differences measured with recalcified plasma samples. For example, the difference between lot 214 and the master lot was –1.6% for fresh blood, but –3.6% to –7.8% for plasma samples. Another example of poor agreement between fresh blood and deep-frozen plasma samples is strip lot number 139, where the INR difference was –2.3% for blood but +0.3% to +3.7% for plasma. In other words, the inter-lot difference for fresh capillary blood samples cannot always be predicted from results obtained with recalcified plasma samples. At this stage we cannot explain why blood and recalcified plasma do not always provide similar results. The origin of the discrepancy should be found in slight variations in the composition of the test strip and its interaction with whole blood and with recalcified plasma. If all strips were identical, there would be no interlot differences between blood and plasma results. In conclusion, we have shown that there were statistically significant differences in the mean INR between some of the six test strip lots. These differences in the mean INR were small as capillary blood samples were used. In individual patients larger dif-