Accuracy assessment of consecutive test strip lots for whole blood INR point-of-care instruments: clarifying the role of frozen plasma pools

Journal of Thrombosis and Haemostasis

Rijn

Abdoel

et al. 2020

Self Cite

Background International normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt tube technique (MTT) for prothrombin time (PT) determination. An important part of the total variability of INR is due to poor harmonization of MTT across WHO reference laboratories. Objectives To determine the origins of PT differences between operators performing MTT and to develop a harmonized MTT. Methods Two workshops were held where WHO reference laboratory operators could compare their PTs using MTT and the same equipment. A harmonized MTT was used by seven operators in the second workshop. Results Differences have been observed in tilting frequency and in the height of pipetting plasma in the test tube. At the beginning of the first workshop, the tilting cycle time varied between 1.1 and 2.7 seconds. The mean PT of normal plasma obtained by pipetting plasma at the top of the tube was 14.3 seconds but was 12.9 seconds when plasma was pipetted at the bottom of the tube. When using the harmonized MTT for WHO International Standard rTF/16, the differences between operators were not greater than 1.1 seconds in normal plasma, and not greater than 1.3 seconds in patient plasma with average INR of 3.0. INR between‐operator coefficient of variation was 2.3%. Conclusion Application of a harmonized MTT in three reference laboratories resulted in substantial reduction of between‐operator variation of PT and INR. The harmonized MTT is proposed as Candidate Reference Measurement Procedure.

Section: Methodsmentioning

confidence: 99%

Section: Deep-frozen and Freeze-dried Plasma Poolsmentioning

confidence: 99%

Paving the way for establishing a reference measurement system for standardization of plasma prothrombin time: Harmonizing the manual tilt tube method

Journal of Thrombosis and Haemostasis

Rijn

Abdoel

et al. 2020

Self Cite

“…One frozen plasma pool was prepared out of 35 healthy adult individual donations (code #12-0). The other five plasma pools were prepared of patients receiving VKA, essentially as described previously [9]. These pools were made from samples collected according to the following INR ranges: 1.5-2.0 (code #12-1), 2.0-2.4 (code #12-2), 2.4-2.8 (code #12-3), 2.8-3.2 (code #12-4), and 3.2-3.6 (code #12-5).…”

Section: Preparation Of Deep-frozen Plasma Poolsmentioning

confidence: 99%

“…Commutability is a requirement for the application of EQA results in the evaluation of the performance of participating laboratories in terms of standardization of their measurements [7]. Only very few studies have addressed the commutability of EQA materials with regard to INR [8,9].…”

Section: Introductionmentioning

confidence: 99%

Assignment of international normalized ratio to frozen and freeze-dried pooled plasmas

Clinical Chemistry and Laboratory Medicine (CCLM)

Cobbaert

2020

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ObjectivesFrozen and freeze-dried plasmas may be used for local prothrombin time system calibration, for direct international normalized ratio (INR) determination, and for quality assessment. The purpose of the present study was to evaluate the usefulness of INRs assigned with various types of thromboplastins to frozen and freeze-dried pooled plasmas obtained from patients treated with vitamin K antagonists.MethodsINRs were calculated according to the international sensitivity index (ISI) model using various thromboplastins and instruments, i.e. International Standards for thromboplastin as well as six commercial reagents prepared from rabbit and bovine brain, and recombinant human tissue factor. The uncertainty of the INRs was assessed using the standard deviations of clotting times and ISI values. Commutability of the plasmas was assessed according to the approved Clinical and Laboratory Standards Institute (CLSI) Guideline EP30-A. Validation of a set of six frozen plasma pools for direct INR determination was performed according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (SSC/ISTH) guidelines.ResultsFor all frozen and freeze-dried plasmas, the INRs calculated with bovine thromboplastin Thrombotest were lower than the INRs assigned with other thromboplastins. With a few exceptions, the frozen and freeze-dried pooled plasmas were commutable. When the set of six frozen plasma pools was used for local calibration, the analytical bias of the INR was less than ±10% for all commercial reagents except Thrombotest.ConclusionsProcessing of fresh plasmas to prepare pooled frozen plasmas and freeze-dried plasmas may lead to different INR assignments depending on the thromboplastin used. Despite minor INR differences, a set of six frozen plasma pools could be used for local calibration by direct INR determination.

“…In this procedure, results are used to calculate the INR bias for each lot of imported test strips in relation to the appropriate International Standard for thromboplastin established by the World Health Organization (WHO). Before we reported on the assessment of bias in 54 consecutive test strip lots using the previous International Standard for thromboplastin coded rTF/09 as reference [3]. In that study, we used only the average INR of patient's blood samples to calculate the mean bias for each new lot of test strips.…”

Section: Introductionmentioning

confidence: 99%

Bias and uncertainty of the International Normalized Ratio determined with a whole blood point-of-care prothrombin time test device by comparison to a new International Standard for thromboplastin

Rijn

Abdoel

et al. 2021

Thrombosis Research

Self Cite

Background: Whole blood point-of-care PT/INR test devices, e.g. CoaguChek XS, are calibrated by their manufacturers. In the Netherlands, each new lot of test strips for CoaguChek XS is validated by a group of anticoagulant clinics collaborating with a Coagulation Reference Laboratory. In 2017, a new International Standard for recombinant human thromboplastin (coded rTF/16) has been established by the World Health Organization. Aim: To assess uncertainty of the validation procedure and the magnitude of the INR bias of a series of consecutive lots of test strips imported in the Netherlands. Methods: CoaguChek XS test strip INR results were compared to INRs determined with the new International Standard rTF/16. Comparisons were made with variable numbers of blood samples obtained from patients treated with vitamin K-antagonists. Relationships between CoaguChek XS and rTF/16 results were determined with orthogonal regression analysis. The relationships were used to assess bias and uncertainty of bias. Results: Average bias between CoaguChek XS test results and rTF/16 depends on the INR level. Overall, there was a trend of increasing bias and increasing uncertainty with increasing INR values. Along the sequence of 47 consecutive lots, a temporary fluctuation of bias was observed. At an INR level of 3.0 the average bias was less than 10% in all cases, but at an INR of 4.0 there were 5 lots with average bias between 10 and 15%. Conclusion:Validation of test strips is useful to assess bias but depends on availability of fresh patients' samples and traceability to an accepted Reference Measurement System.