Preparation of control blood for external quality assessment of point-of-care international normalized ratio testing in the Netherlands.

Objectives: The aim of this study was to prepare control blood for an external quality assessment scheme (EQAS) for international normalized ratio (INR) point-of-care testing (POCT) in the Netherlands and to assess the performance of the participants.

Methods: Control blood was prepared from dialyzed pooled patient plasma and washed human erythrocytes. Samples of control blood were mailed to participants of the Netherlands EQAS from October 2006 through December 2012.

A comparative study of conventional versus new, magnesium-poor Vacutainer® Sodium Citrate blood collection tubes for determination of prothrombin time and INR.

Introduction: Conventional Vacutainer® Sodium Citrate blood collection tubes contain a relatively high concentration of contaminating magnesium ions, which may result in shortening of the prothrombin time (PT) and the International Normalized Ratio (INR). Recently the manufacturer of Vacutainer® Sodium Citrate tubes introduced new tubes with a magnesium-poor stopper. The magnesium concentration in the new low-Mg tubes is significantly lower than that in the conventional plastic tubes.

Long-term stability of frozen pooled plasmas stored at -70°C, -40°C, and -20°C for prothrombin time and International Normalized Ratio (INR) assessment.

Background: Frozen pooled plasmas may be used for quality assessment and local calibration of prothrombin time (PT) and International Normalized Ratio (INR) measurement systems. The purpose of the present study is to estimate the long-term stability of frozen pooled plasmas stored for at least three years.

Methods: Six pooled plamas with different INR levels were stored at -70°C, -40°C, and -20°C for various time periods up to 1453days.

Comparative study of blood collection tubes and thromboplastin reagents for correction of INR discrepancies: a proposal for maximum allowable magnesium contamination in sodium citrate anticoagulant solutions.

International normalized ratio (INR) discrepancies were noted between clinical laboratories using various prothrombin time (PT) systems. We studied the influence of different commercial blood collection tubes and different PT systems on INR measurements. INRs of fresh patient samples were determined by 3 laboratories, each using different PT systems.

Point-of-care monitoring of vitamin K-antagonists: validation of CoaguChek XS test strips with International Standard thromboplastin.

Aims: Many patients treated with vitamin K-antagonists (VKA) use point-of-care (POC) whole blood coagulometers for self-testing. The majority of patients in the Netherlands use one type of POC coagulometer, that is, the CoaguChek XS. Each new lot of test strips for the CoaguChek XS is validated by a group of collaborating thrombosis centres.

Biological variation of INR in stable patients on long-term anticoagulation with warfarin.

Within-individual biological variation of INR (CV(B)) was assessed in 245 selected stable warfarin-treated patients monitored by three thrombosis centers. Selection criteria were: treatment period of six months or longer before the observation period; at least six consecutive INRs within the therapeutic range of 2.0 - 3.

Harmonization and external quality assessment of antithrombin activity assays.

Unlabelled: In the framework of a Dutch project named "Calibration 2000" harmonization of antithrombin activity assays was studied. The commutability of potential calibrators for antithrombin was assessed by means of a twin-study design, which is a multicentre, split-patient sample, between-field-methods protocol. The twin-study consisted of simultaneous analysis of fresh-frozen patient plasmas and three potential calibrators for antithrombin by 30 Dutch laboratories forming 15 couples.

Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements.

Within each patient treated with vitamin K antagonist (VKA), variation of the international normalised ratio (INR) occurs over the treatment period. The purpose of the present study was to assess INR variation in selected patients on long-term treatment in whom the dose of VKA was not changed. This type of variation is considered as "biological variation" which is caused by many factors but not VKA dose changes or other medication.

A multicentre randomised assessment of the DAWN AC computer-assisted oral anticoagulant dosage program.

Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of "time in target INR range" (TIR) not on clinical safety in practice.

Influence of haematocrit on international normalised ratio (INR) differences between a whole blood point-of-care coagulation monitor and reference prothrombin time in plasma.

The CoaguChek S system is designed for use in patient self-testing. In this system a whole blood sample without sodium citrate is applied to a test strip containing thromboplastin and iron oxide particles. The detection principle is based on fibrin formation which inhibits and finally stops the movement of the iron oxide particles.

Multicentre ISI assignment and calibration of the INR measuring range of a new point-of-care system designed for home monitoring of oral anticoagulation therapy.

The new CoaguChek XS system is designed for use in patient selftesting. It is the successor of the current CoaguChek S system. The detection principle is based on the amperometric measurement of the thrombin activity initiated by starting the coagulation cascade using a human recombinant thromboplastin.

Influence of blood collection systems on the prothrombin time and international sensitivity index determined with human and rabbit thromboplastin reagents.

Three brands of blood collection tubes were studied for their influence on the prothrombin time (PT) and international sensitivity index (ISI) for 5 commercial thromboplastin reagents. With all reagents, PTs were shorter in Vacutainer (Becton Dickinson Vacutainer Systems, Plymouth, England) samples than in S-Monovette (Sarstedt, Nümbrecht, Germany) or Venosafe (Terumo Europe, Leuven, Belgium) samples. ISI values were higher with Vacutainer samples than with S-Monovette or Venosafe samples.

A national field study of quality assessment of CoaguChek point-of-care testing prothrombin time monitors.

A system for quality assessment (QA) of the CoaguChek (Roche Diagnostics, Mannheim, Germany) point-of-care testing prothrombin time monitor has been developed by the European Concerted Action on Anticoagulation. Hitherto there has not been an adequate rapid method for CoaguChek QA. Sets of 5 certified international normalized ratio (INR) plasma samples were tested on 539 CoaguChek monitors by experienced staff at 9 Netherlands Thrombosis Centers and results compared with certified INR.

Quality assessment of CoaguChek point-of-care prothrombin time monitors: comparison of the European community-approved procedure and conventional external quality assessment.

Background: There is a need for dependable quality assessment (QA) of the widely used CoaguChek point-of-care testing prothrombin time monitor. By use of the prescribed set of 5 CoaguChek certified international normalized ratio (INR) QA plasmas, we compared the reliability of the immediate QA of individual monitors described in the European Community-recommended Technology Implementation Plan with conventional external QA analysis.

Methods: Experienced staff tested CoaguChek point-of-care monitors in routine use for controlling oral anticoagulant dosage at 9 Netherlands Thrombosis Service Centres.

Long-term stability of relationships between reference materials for thromboplastins.

Reference materials for thromboplastins are available from the World Health Organization (WHO) and the European Commission (EC). The long-term stability of the reference materials is an essential requirement and must be monitored. The relationship between two reference materials for rabbit thromboplastin, i.

Harmonisation of factor VIII:C assay results: study within the framework of the Dutch project 'Calibration 2000'.

In a Dutch project for harmonisation of factor VIII coagulant activity (FVIII:C) assays, the commutability of potential calibrators for FVIII:C was assessed by means of a 'twin-study design', which is in essence a multi-centre, split-patient sample, between-field-methods protocol. Commutability was defined as the degree to which a material yielded the same numerical relationships between results of measurements by a given set of measurement procedures as those between the expectations of the relationships for the same procedures applied to those types of material for which the procedures were intended. The study consisted of the simultaneous analysis of fresh frozen patient plasmas and three potential calibrators for FVIII:C by 16 Dutch laboratories forming eight couples.

Long-term stability and reproducibility of CoaguChek test strips.

Whole-blood point-of-care testing prothrombin time monitors are being used on an increasing scale for the monitoring of oral anticoagulant therapy. These monitors are used with disposable test strips containing tissue factor reagent. The purpose of the present study was to assess the stability of different CoaguChek-S strip lots for a period of one year.

Preanalytical variables and off-site blood collection: influences on the results of the prothrombin time/international normalized ratio test and implications for monitoring of oral anticoagulant therapy.

Background: The quality of oral anticoagulant therapy management with coumarin derivatives requires reliable results for the prothrombin time/International Normalized Ratio (PT/INR). We assessed the effect on PT/INR of preanalytical variables, including ones related to off-site blood collection and transportation to a laboratory.

Methods: Four laboratories with different combinations of blood collection systems, thromboplastin reagents, and coagulation meters participated.

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.

Use of lyophilized calibrant plasmas for simplified international normalized ratio determination with a human tissue factor thromboplastin reagent derived from cultured human cells.

Background: For monitoring of treatment with oral anticoagulants, the clotting time obtained in the prothrombin time (PT) test is transformed to the International Normalized Ratio (INR) with use of a system-specific International Sensitivity Index (ISI). The calibrant plasma procedure (CPP) is an alternative approach to INR calculation based on the use of a set of lyophilized plasmas with assigned INRs.

Methods: With the CPP, a linear relationship is established between log(PT) and log(INR), using orthogonal regression.

European Concerted Action on Anticoagulation. Correction of displayed international normalized ratio on two point-of-care test whole-blood prothrombin time monitors (CoaguChek Mini and TAS PT-NC) by independent international sensitivity index calibration.

The international normalized ratio (INR) on two widely used point-of-care test (POCT) prothrombin time (PT) monitors (CoaguChek Mini and TAS PT-NC) differed considerably and also differed from the 'true' INR obtained on the same samples using a manual PT and the same species thromboplastin international reference preparation. Agreement between the displayed INR and difference from 'true' INR has been reassessed following an independent international sensitivity index (ISI) calibration of the two systems. The displayed INRs taken at seven centres were compared with 'true' INRs from the same blood donations and INRs based on the resulting ISI.

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.

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.

The influence of exogenous magnesium chloride on the apparent INR determined with human, rabbit, and bovine thromboplastin reagents.

Magnesium ions can shorten the tissue factor-induced coagulation time. Some blood collection systems with sodium citrate are contaminated with variable amounts of magnesium and influence the results of the prothrombin time (PT) test. The aim of the study was to determine the dose-response relationship between exogenous magnesium chloride added to blood and the PT and the international normalized ratio (INR).