Optimizing the Verification of Mean Normal Prothrombin Time (MNPT) and International Sensitivity Index (ISI) for Accurate Conversion of Prothrombin Time (PT) to International Normalized Ratio (INR)

2017 ◽  
pp. 59-74 ◽  
Author(s):  
Emmanuel J. Favaloro
Keyword(s):  
Prothrombin Time ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
International Sensitivity Index

Multicenter Evaluation of Lyophilized and Deep-frozen Plasmas for Assignment of the International Normalized Ratio

1999 ◽  
Vol 82 (11) ◽  
pp. 1451-1455 ◽  
Author(s):  
L. L. Houbouyan-Reveillard ◽  
M. F. Aillaud ◽  
K. W. E. Denson ◽  
C. Droullé ◽  
M. Johnston ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
External Quality Assessment ◽  
Calibration Procedure ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Local Calibration ◽  
External Quality ◽  
Different Types ◽  
Time Systems ◽  
International Sensitivity Index

SummaryThe interlaboratory variation of the International Normalized Ratio (INR) in various external quality assessment schemes is still relatively high. This is partly caused by inaccuracy of manufacturers’ stated International Sensitivity Index (ISI) and/or local instrumentation effects. The interlaboratory variation and accuracy of INR determinations may be improved by a local calibration procedure based on lyophilized plasmas with assigned INRs. The purpose of the present study was to determine INR values for different types of lyophilized plasmas to be used for local calibration. A total of 13 lyophilized plasmas (one normal, six from coumarin-treated patients, six artificially depleted) were analyzed by 10 laboratories, each using five calibrated prothrombin time (PT) systems. INRs were calculated for each plasma using each laboratory’s specific ISI and mean normal prothrombin time values. In the same way, five deep-frozen pooled plasmas from coumarin-treated patients were analyzed. There were significant INR differences for the lyophilized plasmas between the prothrombin time systems. The differences were relatively small for the deep-frozen coumarin plasmas (CV 2.6-3.3%) and three lyophilized coumarin plasmas from one manufacturer (CV 3.7-4.8%). Important INR differences were observed for three lyophilized coumarin plasmas from another manufacturer (CV 9.5-14.1%) and several artificially depleted plasmas (CV 5.3-12.8%). The citrate concentrations in the artificially depleted plasmas were lower than those in the normal and coumarin plasmas. These differences should be considered in the selection and certification of plasmas as calibrants for local calibration of PT systems. The lyophilized plasmas’ INR values obtained in the present study will be used for a field study of local PT calibration to assess their efficacy.

How to Generate a More Accurate Laboratory-Based International Normalized Ratio: Solutions to Obtaining or Verifying the Mean Normal Prothrombin Time and International Sensitivity Index

2018 ◽  
Vol 45 (01) ◽  
pp. 010-021 ◽  
Author(s):  
Emmanuel Favaloro
Keyword(s):  
Prothrombin Time ◽  
Vitamin K Antagonists ◽  
Anticoagulation Therapy ◽  
Clinical Importance ◽  
International Normalized Ratio ◽  
Secondary Process ◽  
Sensitivity Index ◽  
Thrombotic Risk ◽  
Laboratory Test Results ◽  
International Sensitivity Index

AbstractAlthough the landscape of anticoagulation therapy is evolving, vitamin K antagonists (VKAs) such as warfarin remain an anticoagulant of choice for many clinicians and their patients. Nevertheless, management of VKA therapy remains challenging, largely because of patient variability and drug and food interactions; thus, VKA dosing has to be personalized. This is achieved by regular monitoring using a test called the prothrombin time (PT), mathematically converted to an international normalized ratio (INR). The INR system is meant to harmonize laboratory test results by taking into account reagent and instrumentation variability that is otherwise expected to give rise to variable PT values, but which should accordingly lead to less variable INR values. Of clinical importance, too low an INR is suggestive of increased thrombotic risk and typically means the VKA dose should be increased, whereas too high an INR is suggestive of increased bleeding risk and typically means the VKA dose should be temporarily withheld and/or decreased. However, evidence continues to show that variability in INR values between laboratories remains unacceptably high. Given that modern instrumentation provides for robust analytical values—meaning highly reproducible intralaboratory clotting times or PTs in this case—the most likely cause of high INR variability is inconsistency in the INR test components—meaning the MNPT (mean normal PT) and ISI (international sensitivity index) values used by laboratories to generate a given INR. In other words, there are doubts as to the accuracy of some INR values because there are corresponding doubts about the accuracy of MNPT and/or ISI values that have been assigned by some laboratories for their reagent/instrument combination. The current report is intended to provide some solutions around the problems of inaccurate INRs, ISIs, and MNPTs, thus aiming to drive laboratory INRs closer to “truth,” and thus promote better patient management. The novel strategies include a primary process of transference to obtain/verify MNPT and/or ISI values for a new reagent using an existing reagent as reference, and a secondary process whereby external quality assessment data can be used to correct bias or existing errors in assigned MNPT and/or ISI values.

scholarly journals Simplified Method for International Normalized Ratio (INR) Derivation Based on the Prothrombin Time/INR Line: An International Study

2010 ◽  
Vol 56 (10) ◽  
pp. 1608-1617 ◽  
Author(s):  
Leon Poller ◽  
Saied Ibrahim ◽  
Michelle Keown ◽  
Albert Pattison ◽  
Jørgen Jespersen
Keyword(s):  
Prothrombin Time ◽  
Independent Set ◽  
International Study ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Concerted Action ◽  
Total Proportion ◽  
The Mean ◽  
Certified Values ◽  
International Sensitivity Index

BACKGROUND The need to perform local International Sensitivity Index (ISI) calibrations and in particular the requirement for a manual method for prothrombin time (PT) determination, have proved to be obstacles to application of the WHO scheme for PT standardization. METHODS We used international normalized ratio (INR) derived with a set of only 5 European Concerted Action on Anticoagulation (ECAA) lyophilized calibrant plasmas, certified manually by expert centers with reference thromboplastins, to determine a local PT/INR Line. We compared results of an independent set of validation plasmas with INRs from conventional ISI calibrations and with manually certified INRs. RESULTS The mean certified INR of 5 lyophilized validation plasmas was 2.41 with human thromboplastin, 2.04 with bovine/combined, and 2.80 with rabbit. With 42 human reagents, the mean observed INR of the validation plasmas was 2.68 (11.2% deviation from certified INR). Deviation was reduced to 0.4% with both local ISI calibration and the PT/INR Line. Eight results based on bovine/combined thromboplastin gave an INR deviation of 4.9%, becoming 0.5% after ISI calibration and 2.4% with the PT/INR Line. Six results with rabbit reagents deviated from certified INR by 2.5%. After ISI calibration, deviation became 1.1%, and with the PT/INR Line, 0.7%. The PT/INR Line gave similar results with both linear and orthogonal regression analysis. The total proportion of validation plasmas giving INR within 10% deviation from certified values was 42.5% with uncorrected INR, which increased to 92.1% with local ISI calibration and 93.2% with the PT/INR Line. CONCLUSIONS The PT/INR Line procedure with 5 ECAA calibrant plasmas successfully substitutes for local ISI calibrations in deriving reliable INRs.

Thromboplastin Composition Affects the Sensitivity of Prothrombin Time (PT) Clotting Tests To Direct Factor Xa Inhibitors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 928-928 ◽  
Author(s):  
Stephanie A. Smith ◽  
James H. Morrissey
Keyword(s):  
Prothrombin Time ◽  
Tissue Factor ◽  
Factor Xa ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Assay Sensitivity ◽  
Direct Factor Xa Inhibitors ◽  
Normal Human ◽  
International Sensitivity Index

Abstract Introduction: Thromboplastin reagents used for prothrombin time (PT) clotting assays vary in their sensitivity to anticoagulant drugs that directly inhibit Factor Xa (FXa). The International Sensitivity Index (ISI)/International Normalized Ratio (INR) system was introduced for monitoring warfarin, and corrects for differences in PT assay sensitivity. However, it does not adequately correct for differences in assay sensitivity to direct FXa inhibitors. The objective of this study was to determine how the composition of thromboplastin reagents affects PT sensitivity to the novel oral, direct FXa inhibitor rivaroxaban and how this correlates with the INR. Methods: Several recombinant thromboplastin reagents were prepared using different concentrations of NaCl, tissue factor and phospholipids (PL). They also contained different % of phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). These locally prepared thromboplastin reagents and five commercial thromboplastin assays were evaluated. PT ratios (PTR = PT with drug/PT without drug) were measured using normal human plasma to which rivaroxaban 1 μg/mL was added in vitro. Some PTRs were converted to INRs using locally determined ISI. Results: PT obtained with commercial thromboplastins was prolonged by rivaroxaban (Table), but the magnitude varied more than 3-fold, depending on the thromboplastin. Converting PTR to INR failed to normalize these results and made discrepancies more pronounced. Using locally prepared thromboplastin reagents, the PT sensitivity toward rivaroxaban was found to increase by decreasing the concentration of tissue factor or by increasing the concentration of PL or NaCl. Increasing the % PS generally decreased rivaroxaban sensitivity, while including PE generally increased rivaroxaban sensitivity. There was also a trend toward higher rivaroxaban sensitivity as the baseline PT increased. As with commercial thromboplastins, converting these PTR values to INR frequently made the discrepancies more pronounced. Conclusions: Changing the composition of thromboplastin reagents had disparate effects on the sensitivity of PT clotting tests to rivaroxaban. Furthermore, converting PTR values to INR failed to eliminate, and in some cases even exacerbated, the apparent differences in assay sensitivity of these PT clotting tests to rivaroxaban. This study sheds new light on the shortfall of the ISI/INR system to adequately correct for variation in the sensitivity of PT tests to direct FXa inhibitors. However, data show that other global clotting tests, such as PT, can be used to assess the efficacy of direct FXa inhibitors. Table 1: PT results for normal plasma spiked with 1 μg/ml rivaroxaban using commercial thromboplastins Commercial thromboplastins ISI PTR INR INR, International Normalized Ratio; ISI, International Sensitivity Index; PTR, prothrombin time ratio Recombiplastin 0.94 5.07 4.60 Innovin 0.98 2.25 2.22 Thromborel S 1.07 2.37 2.52 Neoplastine CL+ 1.09 7.32 8.76 Thromboplastin C+ 1.50 3.77 7.31

International Normalized Ratio (INR) – Proficiency Tests by ÖQUASTA for the Prothrombin Time

1995 ◽  
Vol 15 (01) ◽  
pp. 41-48 ◽  
Author(s):  
B. Scheer ◽  
B. Moritz ◽  
E. Legenstein ◽  
E. Kaiser ◽  
M. Fischer ◽  
...  
Keyword(s):  
Quality Control ◽  
Prothrombin Time ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Proficiency Tests ◽  
Independent Manner ◽  
Mean Values ◽  
Fresh Plasma ◽  
Value Determination ◽  
International Sensitivity Index

SummaryAlthough the INR (International Normalized Ratio)/ISI (International Sensitivity Index) scheme was introduced by the WHO (13) in 1983 to standardize the PT (prothrombin time) expression, the use of the non-comparable percent of a normal fresh plasma, seconds or PT-ratio (patient plasma/normal plasma) is still common in the coagulation laboratories. The availability of the INR/ISI scheme to monitor quality control of the laboratories in a reagent and method independent manner was examined by the comparison of 13 PT proficiency tests carried out by the ÖQUASTA (Austrian Society of Quality Assurance and Standardization of Diagnostic Medical Investigations).In each proficiency test approximately 250 laboratories had to determine the PT of two to three lyophilized plasma samples with their routinely used reagents and methods. The INR mean values of the AK-plasmas (plasmapools from patients under anticoagulant therapy) were between 2 and 5. The determined data and the calculated INR-values were returned to the ÖQUASTA.According to the INR/ISI scheme, all data should be considered as belonging to the same collective (TC = total collective). To prove this demand, additionally each reagent and method was evaluated separately (SC = single collective). It could be shown that the INR mean values obtained from all data and using TC or SC evaluation are nearly equivalent indicating that the TC evaluation is suitable for use in proficiency tests.The aim of a better comparability of the PT values can not only be reached by the laboratories through the use of the INR/ISI scheme. Additionally, the manufacturer are asked to standardize their ISI and 100% value determination. The manufacturer took this into account by establishing a candidate reference plasma (5).It could be shown that the introduction of the INR was not only an important step forward in terms of standardization and comparability of different thromboplastin reagents, but also in the quality control of the laboratories checked in proficiency tests in Austria.

The Effect of Some Instruments for Prothrombin Time Testing on the International Sensitivity Index (ISI) of Two Rabbit Tissue Thromboplastin Reagents

1989 ◽  
Vol 62 (03) ◽  
pp. 868-874 ◽  
Author(s):  
Marina Poggio ◽  
Antonius M H P van den Besselaar ◽  
Edo A van der Velde ◽  
Rogier M Bertina
Keyword(s):  
Prothrombin Time ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
World Health ◽  
Sensitivity Index ◽  
Optical Instruments ◽  
Rabbit Tissue ◽  
Reference Preparation ◽  
Health Organization ◽  
International Sensitivity Index

SummaryTwo commercial rabbit tissue thromboplastins were calibrated against the International Reference Preparation for rabbit thromboplastin (coded RBT/79) by one laboratory using the manual technique, a semi-automatic electro-mechanical coagulometer and three different automatic photo-optical instruments. The calibration of the two reagents was performed in three and two different exercises, respectively, and showed good reproducibility of the procedure. The purpose of calibration is providing a formula for the assessment of the International Normalized Ratio (INR) for patients receiving oral anticoagulants. The World Health Organization (WHO) model for thromboplastin calibration leads to the equation INR = RISI, in which R is the prothrombin time ratio and ISI the International Sensitivity Index of the calibrated thromboplastin/instrument system. This equation was adequate for one reagent, but not for the other when it was used in combination with the four instruments. At therapeutic intensities of anticoagulation, the deviation from the WHO-model observed for the second reagent was clinically insignificant. The WHO model was fully adequate when the second reagent was used with the manual technique. For both thromboplastins, there were statistically significant differences in ISI between the four instruments. The largest difference-amounting to approximately 10%-was observed between two photo-optical instruments. The order of instruments with increasing ISI was the same for the two reagents. It is recommended that thromboplastin manufacturers specify the instruments used for calibration of their reagent.

scholarly journals Laboratory Wise Variations in Prothrombin Time - INR - A Cross Sectional Study in Trivandrum, Kerala

2021 ◽  
Vol 8 (24) ◽  
pp. 2112-2116
Author(s):  
Shahana Jahan Kulathinte Meethal ◽  
Ravikrishnan Jayakumar ◽  
Suresh Kumar Sreenivasan ◽  
Shaffeek Abdul Majeed ◽  
Indira Kariveettil
Keyword(s):  
Mitral Valve ◽  
Prothrombin Time ◽  
International Normalized Ratio ◽  
P Value ◽  
Sensitivity Index ◽  
Two Samples ◽  
Significant Difference ◽  
The Mean ◽  
Post Hoc ◽  
International Sensitivity Index

BACKGROUND Prothrombin time (PT) is routinely used as a test of coagulation. Thromboplastin is the key ingredient in the reagent for this test. Prothrombin time international normalized ratio (INR) readings can vary according to the thromboplastin used in the reagent. The composition of thromboplastin reagents can influence the sensitivity of each batch of reagents. Various thromboplastin reagents having different international sensitivity index (ISI) values are available now. This study was intended to evaluate the effect of different thromboplastins on INR reading for mitral valve replaced patients under stable oral anticoagulant therapy. METHODS The study was conducted on the citrated plasma received from the mitral valve replaced patients having stable international ratio between 2 to 3 for three months. 62 samples were collected from the clinical pathology laboratory, Govt. Medical College, Trivandrum. Each sample was tested with different thromboplastin reagents having international sensitivity index 1.0, 1.1 and 1.6 by measurement of the prothrombin time and conversion into international normalized ratio. The INR obtained from the thromboplastin with international sensitivity index 1.0 was considered as the standard. INR results obtained from samples tested with thromboplastin reagents with ISI 1.1 and 1.6 were compared with the standard by using analysis of variance (ANOVA) and Dunnett’s post hoc tests. RESULTS Sixty-two samples were tested with the thromboplastin reagent having ISI – 1.0, the mean INR is 2.42, for ISI – 1.1 mean INR value is 2.53 and for ISI 1.6, the mean INR value is 3.19. While comparing the mean value of INR for different reagents using ANOVA, the F value was 14.86, which was significant. P value less than 0.01. In the Dunnett post hoc test, the P value of difference between ISI 1.0/1.6 was < 0.01. Between ISI 1.1/1.6 also the P value is < 0.01. Both of these were significant. The P value of difference between the reagents having ISI 1.0 and 1.1 is 0.838 which denotes no significant difference. CONCLUSIONS In conclusion, the thromboplastin reagent with ISI 1.0 or nearest to 1.0 is most desirable for accurate INR report. KEYWORDS Prothrombin Time, International Sensitivity Index, International Normalized Ratio

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