A Simple Nomogram for the Derivation of International Normalised Ratios for the Standardisation of Prothrombin Times

1988 ◽  
Vol 60 (01) ◽  
pp. 018-020 ◽  
Author(s):  
L Poller
Keyword(s):  
Prothrombin Time ◽  
Sensitivity Index ◽  
General Application ◽  
International Reference ◽  
International Scale ◽  
Alternative Formula ◽  
Local Ratio ◽  
Reference Preparation ◽  
International Sensitivity Index ◽  
Scientific Calculator

SummaryThe WHO international scale of reporting prothrombin time results is based on the calibration of local and commercial thromboplastin reagents used in the test against an international reference preparation to derive an International Sensitivity Index (ISI) for each batch of local reagent. This quantifies an individual reagent’s responsiveness to the coumarin induced defect.Once the ISI has been assigned, the derivation of International Normalised Ratios (INR) for reporting results depends on the use of a scientific calculator by which the local ratio is raised to the power of the ISI of the local reagent or use of an alternative formula and logarithms.A system for interpretation of INR, without the need for calculations, is presented for the known range of thromboplastins between 1.0 and 3.0 ISI in nomogram form. This chart may facilitate the general application of the INR system.

The Calibration of the Second Primary International Reference Preparation for Thromboplastin (Thromboplastin, Human, Plain, Coded BCT/253)

1984 ◽  
Vol 52 (03) ◽  
pp. 336-342 ◽  
Author(s):  
Jean M Thomson ◽  
J A Tomenson ◽  
L Poller
Keyword(s):  
Statistical Analysis ◽  
Prothrombin Time ◽  
International System ◽  
Second Primary ◽  
Sensitivity Index ◽  
Calibration Model ◽  
International Reference ◽  
Reference Preparation ◽  
Time Test ◽  
International Sensitivity Index

SummaryAn international collaborative exercise has been undertaken to calibrate a replacement for the first WHO primary international reference preparation (IRP) for thromboplastin. The replacement preparation is a lyophilised batch of British Comparative Thromboplastin (BCT/253, human plain) for use in the Quick prothrombin time test. Seventeen centres participated. The experimental design, calibration model and statistical analysis were based on the recommended WHO procedure. As a result of this calibration exercise an International Sensitivity Index (ISI) of 1.1 has been assigned to the preparation by WHO and it has been officially recognised as the second primary IRP for thromboplastin.The calibration of BCT/253 is an essential link in a new hierarchical structure for the standardisation of the prothrombin time. The aim is to provide a uniform international system of reporting prothrombin time results using International Normalised Ratios (INR) derived from the ISI of individual thromboplastins.

The Dependence of the International Sensitivity Index on the Coagulometer Used to Perform the Prothrombin Time

1990 ◽  
Vol 63 (03) ◽  
pp. 424-429 ◽  
Author(s):  
M J Ray ◽  
I R Smith
Keyword(s):  
Prothrombin Time ◽  
Reference Method ◽  
Calibration Procedure ◽  
World Health ◽  
Sensitivity Index ◽  
Optical Instruments ◽  
Different Types ◽  
Reference Preparation ◽  
Health Organization ◽  
International Sensitivity Index

SummaryThis study was designed to detect any effect that different types of coagulation instrument may have on the International Sensitivity Index (ISI) of a thromboplastin.Manufacturers of commercial thromboplastins now calibrate their reagents against the World Health Organization international reference preparation to assign them an IST. This enables the prothrombin time (PT) estimated with that reagent to be expressed as an International Normalised Ratio (INR).One batch of Thromborel S was calibrated against the Australasian Reference Thromboplastin (ART). The Thromborel S was used on three photo-optical instruments, the Automated Coagulation Laboratory (ACL) (Instrumentation Laboratory), the Cobas Fibro (Roche), and the Coag-a-Pet (General Diagnostics). PTs using ART were performed manually using the reference method.The ISIs calibrated in our laboratory when the ACL and Cobas Fibro were used were not significantly different at the 95% level, being 1.102 ± 0.018 and 1.134 ± 0.022 respectively. The ISI with the Coag-a-Pet of 1.223 ± 0.023 was significantly different to that of the ACL and the Cobas Fibro at the 95% level.The flowcharts for a computer program to perform the necessary calculations are provided. The program allows for the entry and editing of data from the calibration procedure, and provides a mean normal PT and normal range, the ISI and 95% confidence limits of the calibration, and a chart for the conversion of the test PTs to INRs.The authors have made available an IBM compatible program for the calibration of thromboplastins.

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 Influence of Three Types of Automated Coagulometers on the International Sensitivity Index (ISI) of Rabbit, Human, and Recombinant Human Tissue Factor Preparations

1999 ◽  
Vol 81 (01) ◽  
pp. 66-70 ◽  
Author(s):  
L. L. Houbouyan ◽  
M. F. Aillaud ◽  
K. W. E. Denson ◽  
M. Johnston ◽  
S. Kitchen ◽  
...  
Keyword(s):  
Tissue Factor ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
International Reference ◽  
Rabbit Tissue ◽  
Reference Preparation ◽  
The Mean ◽  
Automated Instruments ◽  
International Multicenter ◽  
International Sensitivity Index

SummaryFive tissue factor reagents and three types of automated instruments for prothrombin time (PT) determination were studied in an international multicenter collaborative exercise. The purpose of this work was to determine the international sensitivity index (ISI) for each combination of reagent and instrument against the international reference preparation RBT/90. Each type of instrument was used by 3 or 4 centers to assess the interlaboratory variation of the ISI. The interlaboratory variation of the ISI for each combination of reagent and instrument ranged between 0.4% and 7.8% coefficient of variation. For three reagents, the mean ISI values for ACL (nephelometric) and STA (mechanical) were practically identical, but the mean ISI values for MLA (photo-optical) were at least 10% higher. For two other reagents prepared from rabbit tissue, the mean ISI values increased in the order ACL, STA, MLA. The widest range of mean ISI values was noted with one rabbit tissue factor reagent: 1.68 for ACL and 2.00 for MLA. Exclusion of patient specimens with INR <1.5 and INR >4.5 determined by the international reference preparation resulted in a slight decrease of the mean ISI.The interlaboratory variation of the International Normalized Ratio (INR) was assessed from the results obtained with common lyophilized and deep-frozen plasmas. The use of instrument-specific ISI values resulted in reduced interlaboratory variation of the INR. It is recommended that thromboplastin manufacturers provide instrument-specific ISI values.

Recombinant Tissue Factor as Substitute for Conventional Thromboplastin in the Prothrombin Time Test

1992 ◽  
Vol 67 (01) ◽  
pp. 042-045 ◽  
Author(s):  
Armando Tripodi ◽  
Arnaldo Arbini ◽  
Veena Chantarangkul ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Prothrombin Time ◽  
Tissue Factor ◽  
Oral Anticoagulant Therapy ◽  
Clotting Factor ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Clotting Factors ◽  
Wide Range ◽  
Reference Preparation ◽  
Time Test

SummaryRelipidated recombinant tissue factor (r-TF) has been assessed in comparison with conventional rabbit brain thromboplastin (Manchester Reagent) for its suitability for measurement of prothrombin time (PT). The International Sensitivity Index (ISI) of r-TF calibrated against the International Reference Preparation BCT/253 (human plain) was found to be 0.96 and 1.12 with instrumental and manual techniques. Our study of plasmas from patients with congenital deficiencies of clotting factors covering a wide range of severity demonstrates that r-TF is able to detect even minor deficiencies of factors involved in the extrinsic and common coagulation pathways. Patients with liver diseases were correctly diagnosed with a prevalence of abnormal results comparable for both reagents. Between-assay reproducibility expressed as coefficient of variation was 2.3 % and 3.9 % at normal and abnormal PT levels.In conclusion, our evaluation shows that relipidated r-TF possesses the necessary requisites of sensitivity, diagnostic accuracy and reproducibility which make it a suitable candidate for PT determination both for monitoring oral anticoagulant therapy and diagnosing congenital and acquired clotting factor deficiencies. Moreover, being a highly defined reagent it may constitute a step forward in the standardization of PT testing.

Questions and Answers on Prothrombin Time Standardisation in Oral Anticoagulant Control

1985 ◽  
Vol 54 (02) ◽  
pp. 515-517 ◽  
Author(s):  
E A Loeliger ◽  
L Poller ◽  
M Samama ◽  
J M Thomson ◽  
A M H P Van den Besselaar ◽  
...  
Keyword(s):  
Plasma Sample ◽  
Oral Anticoagulants ◽  
Sensitivity Index ◽  
International Normalised Ratio ◽  
Questions And Answers ◽  
Reference Preparation ◽  
Tissue Thromboplastin ◽  
The Individual ◽  
International Sensitivity Index ◽  
New System

SummaryOne of the reasons why oral anticoagulants fell into disrepute is the absence of internationally accepted standardised procedures for controlling the level of anticoagulatiori. This deplorable situation resulted in over- and under-coagulation and uncertainty in the therapeutic range. International conformity can now be obtained by using an International Normalised Ratio (INR) which is derived from the individual result obtained in a given plasma sample and the International Sensitivity Index (ISI) of the tissue thromboplastin reagent used. Any thromboplastin reagent can be calibrated against an international primary or secondary W.H.O. reference preparation, so as to obtain its International Sensitivity Index. The new system of reporting the level of anticoagulation was designed and can only safely be applied in patients taking oral anticoagulants.

Assessment of the Influence of Citrate Concentration on the International Normalized Ratio (INR) Determined with Twelve Reagent-instrument Combinations

1998 ◽  
Vol 80 (08) ◽  
pp. 258-262 ◽  
Author(s):  
Veena Chantarangkul ◽  
Marigrazia Clerici ◽  
Barbara Negri ◽  
Pier Mannuccio Mannucci ◽  
Armando Tripodi
Keyword(s):  
External Quality Assessment ◽  
International Normalized Ratio ◽  
Local System ◽  
Sensitivity Index ◽  
External Quality ◽  
Citrate Concentration ◽  
Coagulation Tests ◽  
Reference Preparation ◽  
Anticoagulated Patients ◽  
International Sensitivity Index

SummaryCitrate concentration is one of the variables that can affect coagulation tests. However, few studies have so far been performed to assess the magnitude of this effect on coagulation tests in general and PT in particular. The aim of this study was to assess the extent of influence of citrate concentration on the PT test with results expressed as INR. Twelve reagent-instrument combinations (systems) were calibrated vs. the Reference Preparation BCT/441 using plasmas collected in either 105 mM or 129 mM citrate from normals and anticoagulated patients (OAT). PTs for plasmas collected in 129 mM citrate were longer than those collected in 105 mM both for normals and patients on OAT, but the ratios (patient-to-normal clotting times) for the two citrate concentrations were significantly different in many instances, implying that the International Sensitivity Index (ISI) is also different. ISIs for calibrations with plasmas collected in 105 mM were greater (up to 10%) than those with plasmas collected in 129 mM citrate. When PT ratios were transformed into INR using crossover ISIs (i.e., plasmas collected in 105 mM and ISI determined with plasmas collected in 129 mM citrate, or vice versa) we found that an INR of 4.5 could be up to 20% apart from the value that would have been obtained if the appropriate ISI was used. Moreover, if the ISI determined with the manual technique was used to convert PTs obtained with a particular instrument into INR, the effect of citrate concentration was even greater (INR difference up to 64%). Should these observations be valid for other systems, they might provide additional explanations for the frequent reports which document discrepancies in the INR determined with different systems to which incorrect ISI might have been applied. World-wide consensus on a single citrate concentration to collect patients’ as well as lyophilized plasmas to be used in External Quality Assessment Schemes and for local system calibration is therefore urgently needed.

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.

INR derivation with the PT/INR Line simplified using a spreadsheet from the world wide web

2011 ◽  
Vol 64 (10) ◽  
pp. 930-932 ◽  
Author(s):  
Leon Poller ◽  
Saied Ibrahim ◽  
Albert Pattison ◽  
Jørgen Jespersen ◽  
Keyword(s):  
Linear Regression ◽  
Prothrombin Time ◽  
World Wide ◽  
Linear Regression Analysis ◽  
Sensitivity Index ◽  
Concerted Action ◽  
The World ◽  
Complex Linear ◽  
Local Mean ◽  
International Sensitivity Index

BackgroundThe prothrombin time/international normalised ratio (PT/INR) Line method to derive INR, based on only five European Concerted Action on Anticoagulation (ECAA) certified plasmas, is shown to be reliable in previous ECAA studies. A simpler method not requiring linear regression calculation would be an advantage.MethodAfter determining the local PT/INR Line, local INRs have been obtained using a readily available spreadsheet on the internet which laboratories can use without performing any additional calculations.ResultsExamples of INR derivation have been obtained from results at 16 centres using a range of local coagulometers with human thromboplastin international reference preparations (IRPs). The procedure does not require manual PT testing, local international sensitivity index calibration, availability of thromboplastin IRPs or local mean normal prothrombin time.ConclusionsFrom the PT/INR Line, INR values for local PT results are easily obtained using an Excel spreadsheet from our website (http://www.anticoagulants.co.uk/) which does not require the complex linear regression analysis to derive INR.

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.

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