A multicentre modified World Health Organization (WHO)-type international sensitivity index (ISI) calibration has been performed at 10 European Concerted Action on Anticoagulation (ECAA) national laboratories using non-citrated whole-blood on two point-of-care test (POCT) prothrombin time (PT) monitor systems, CoaguChek Mini and TAS PT-NC, using single lots of test cards/strips. The relevant species (human and rabbit) WHO international reference preparations (IRPs) were tested with the manual PT technique on citrated plasma from the same blood donations. The ISI was calculated from the slope of the orthogonal regression line relating log PT (POCT) to log PT (IRP). The mean ISI of the CoaguChek Mini system was 1.75 and 1.13 with the prothrombin time non-citrated Thrombolytic Assessment System (TAS PT-NC). With the CoaguChek Mini system, seven out of 10 calibrations exceeded the current 3% WHO recommended limit for the coefficient of variation (CV) of the slope with conventional PT testing, whereas with the TAS PT-NC system, it was eight out of 10. All the POCT calibrations had a CV of the slope <5%. It is suggested that this level of precision be adopted as the limit of acceptability of calibration of these monitor systems. In these circumstances, the modified WHO-type ISI calibration appeared to be satisfactory for the POCT whole-blood monitors.
Summary. The success in achieving therapeutic international normalized ratio (INR) targets in the control of warfarin using a whole‐blood point‐of‐care testing (POCT) monitor (CoaguChek) in a community clinic was compared with hospital laboratory coagulometer prothrombin time (PT) testing in a randomized crossover study. Forty‐six patients were randomized into two groups. At each visit, capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer. In Group 1, for 6 months, dosage was based on the CoaguChek and for the second 6 months on the coagulometer. In the second group, the order was reversed. Dosages were determined using the dawn ac computer programme. Success was assessed by the percentage of time patients were maintained within the INR targets. Agreement between laboratory and monitor INR, and patient satisfaction were also assessed. Results with the POCT monitor compared well with the hospital coagulometer. Time in INR target range between the groups was similar, with 60·9% on the POCT monitor and 59·3% with the laboratory coagulometer in Group 1 and in Group 2, respectively, 64·3% and 63·4% with no significant difference in mean INR. An INR above 4·0 gave some discrepant results. International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable. Patient questionnaires showed greater satisfaction with community POCT monitoring.
We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
The international sensitivity index (ISI) calibration of point-of-care-test (POCT) prothrombin time (PT) whole blood monitors is complex, requiring manual PT testing of 60 patients’ and 20 healthy subjects’ plasma samples. The possibility of reducing these numbers was studied by a Monte Carlo Bootstrap study for 2 POCT PT systems. For reduced sample numbers, this consisted of 50,000 calibrations using whole blood and plasma samples tested on the monitors with manual PT testing of plasma samples from the same blood donations. There was little effect on mean ISI by reduction of sample numbers to a total of 7, but there was progressively less certainty regarding the reliability of the calibration. Precision of the calibrations and international normalized ratio deviation were not affected markedly by reducing numbers to half. As ISI calibration with the 2 POCT systems was less precise than conventional manual testing, for maximum confidence, reduction of numbers is not advised.
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