Applications of DNA Diagnosis to Inherited Coagulation Disorders

Haemophilia A, haemophilia B and von Willebrand's disease are the three commonest inherited disorders of coagulation. Genetic counselling at the time this project was undertaken (1985/86) was hampered by the inability of coagulation tests to clearly distinguish carriers from non-carriers for the X-linked haemophilias and by the need for second trimester fetal blood sampling in those families who opted for prenatal diagnosis. The present project aimed to utilise the newly available gene probes for these three conditions to measure their clinical value for improved genetic counselling within affected families

Reliability of international normalised ratios from two point of care test systems: comparison with conventional methods

Objective To find out how accurately two point of care test systems—CoaguChek Mini and TAS PT-NC (RapidPointCoag)—display international normalised ratios (INRs). Design Comparison of the INRs from the two systems with a “true” INR on a conventional manual test from the same sample of blood. Setting 10 European Concerted Action on Anticoagulation centres. Participants 600 patients on long term dosage of warfarin. Main outcome measures Comparable results between the different methods. Results The mean displayed INR differed by 21.3% between the two point of care test monitoring systems. The INR on one system was 15.2% higher, on average, than the true INR, but on the other system the INR was 7.1% lower. The percentage difference between the mean displayed INR and the true INR at individual centres varied considerably with both systems. Conclusions Improved international sensitivity index calibration of point of care test monitors by their manufacturers is needed, and better methods of quality control of individual instruments by their users are also needed

European concerted action on anticoagulation: Minimum numbers of lyophilized plasma samples for ISI calibration of CoaguChek and TAS point-of-care whole blood prothrombin time monitors

International sensitivity index (ISI) calibration of whole blood prothrombin time (PT) monitors is too complex. We previously simplified the method by using European Concerted Action on Anticoagulation (ECAA) lyophilized plasma samples with the TAS PT-NC (Bayer AG, Leverkusen, Germany) and the CoaguChek Mini (Roche Diagnostics, Mannheim, Germany) whole blood PT monitoring systems. The TAS PT-NC required a correction derived from the line of equivalence. Monte Carlo bootstrap analysis of reducing numbers of test samples was performed with both systems. Plasma samples from patients receiving coumarin (coumarin samples), healthy subjects (normal samples), and plasma samples artificially depleted of coagulation factors were used. With the TAS PT-NC, 20 coumarin samples or 20 artificially depleted samples with 7 normal samples gave reliable ISI and international normalized ratio and satisfactory precision. With the CoaguChek Mini, 30 coumarin and 10 normal samples were required. Simplification of ISI calibration of the 2 monitoring systems is possible using fewer ECAA lyophilized plasma samples than the 80 required according to the World Health Organization guidelines for conventional PT systems and previously recommended for fresh plasma samples tested on the same 2 monitoring systems

European Concerted Action on Anticoagulation. Quality Assessment of the CoaguChek Mini and TAS PT-NC Point-of-Care Whole-Blood Prothrombin Time Monitors

BACKGROUND: International Normalized Ratios (INRs) for prothrombin time obtained with the CoaguChek Mini and TAS (RapidPointCoag) PT-NC systems are markedly different and also differ from the "true" INR. There is therefore a need for local quality assessment (QA) of the two systems. METHODS: A set of 60 lyophilized artificially depleted and 60 lyophilized coumarin plasmas were tested at 10 centers on both point-of-care testing monitors. Subsets of three and five plasmas were selected as QA plasmas and compared with the remaining 55 to assess the relative ability of the systems to characterize performance at the individual centers. The incidence of aberrant results (outliers; >15% deviation from the true INR) was also recorded. The expected incidence with the QA plasmas was calculated and compared. RESULTS: On both systems, INR with the common sets of 55 lyophilized plasmas varied considerably between centers. With the TAS PT-NC, subsets of five and three European Concerted Action on Anticoagulation (ECAA) artificially depleted plasmas gave good correlation with the 55 plasmas, but the coumarin plasmas performed less well. With the CoaguChek Mini, correlation was good with sets of five artificially depleted QA plasmas and reasonable with three but was less satisfactory with the coumarin plasmas. Outliers were detected with both types of plasmas on both test systems but with variable success. CONCLUSIONS: With the TAS PT-NC, three ECAA artificially depleted lyophilized plasmas provided reliable QA, but five lyophilized coumarin plasmas were required. With the CoaguChek Mini, five artificially depleted plasmas gave reliable QA but coumarin plasmas gave poorer results. ECAA QA plasmas provide a local system for checking INRs obtained with monitors of both type

Minimum numbers of fresh whole blood and plasma samples from patients and healthy subjects for ISI calibration of CoaguChek and RapidPointCoag monitors

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

External quality assessment (EQA) for CoaguChek monitors

Anticoagulant control facilities are being overwhelmed by requests for monitoring and large numbers of patients are not therefore receiving treatment. Procedures designed for point-of-care testing have therefore been developed, the most popular being the CoaguChek. The need for external quality assessment (EQA) of monitors used by patients in self-management has been stressed in a European Commission (EC) Directive. It would not however be feasible for all CoaguChek monitors to be enrolled in national or regional EQA schemes which take time to organise and analyse. The European Concerted Action on Anticoagulation (ECAA) has therefore evolved a simpler system. Its value has been assessed in collaboration with the European Concerted Action on Thrombosis (ECAT). 523 monitors were tested at nine clinics which asked patients to bring their CoaguChek instruments to be assessed with the ECAA/ECAT procedure based on a set of 5 plasma samples with certified international normalised ratios (INR). 15% or more deviation from the certified INR on a single certified plasma sample from the set was defined by the ECAA as the limit of acceptable performance. One hundred and six (20.3%) of the monitors tested showed significant deviation and higher than average incidence of significant INR deviations reported with one specific numbered lot of test strips. Recent ECAA/ECAT, Danish and Italian studies report regular EQA of CoaguChek monitors is essential. There is general agreement that this should be performed at reasonably frequent intervals, at six months or whenever there is a change of the manufacturer's test strips

Patient satisfaction with point-of-care testing in general practice

BackgroundPoint-of-care testing is increasingly being used in general practice to assist GPs in their management of patients with chronic disease. However, patient satisfaction and acceptability of point-of-care testing in general practice has not been widely studied.AimTo determine if patients are more satisfied with point-of-care testing than with pathology laboratory testing for three chronic conditions.Design of studyAs part of a large multicentre, randomised, controlled trial assessing the use of point-of-care testing in Australian general practice, satisfaction was measured for patients having pathology testing performed by point-of-care testing devices or pathology laboratories. Patients in the trial were managed by GPs for diabetes, hyperlipidaemia, and/or anticoagulant therapy.MethodPatient satisfaction was measured using level of agreement with a variety of statements at the end of the study with a patient satisfaction questionnaire for both the intervention and control groups. Analysis was performed using a mixed model analysis of variance (ANOVA) with allowance for clustering at the practice level following Box-Cox transformations of the data to achieve normality.ResultsOverall, intervention patients reported that they were satisfied with point-of-care testing. In comparison with the control group, the intervention group had a higher level of agreement than control patients with statements relating to their satisfaction with the collection process (PConclusionThe results from this trial support patient satisfaction and acceptability of point-of-care testing in a general practice setting.Caroline O Laurence, Angela Gialamas, Tanya Bubner, Lisa Yelland, Kristyn Willson, Phil Ryan, Justin Beilby, and the Point of Care Testing in General Practice Trial Management Grou