Multi-Center Study of Thromboplastin Calibration Precision – Influence of Reagent Species, Composition, and International Sensitivity Index (ISI)

1993 ◽  
Vol 69 (01) ◽  
pp. 035-040 ◽  
Author(s):  
A M H P van den Besselaar ◽  
R M Bertina
Keyword(s):  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
The Other ◽  
World Health ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Bovine Plasma ◽  
Significant Difference ◽  
The Mean ◽  
International Sensitivity Index

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.

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

Effect of Concentration of Trisodium Citrate Anticoagulant on Calculation of the International Normalised Ratio and the International Sensitivity Index of Thromboplastin

1994 ◽  
Vol 72 (01) ◽  
pp. 084-088 ◽  
Author(s):  
E M Duncan ◽  
C R Casey ◽  
B M Duncan ◽  
J V Lloyd
Keyword(s):  
Reference Material ◽  
Oral Anticoagulants ◽  
Reference Method ◽  
Trisodium Citrate ◽  
Sensitivity Index ◽  
Blood Samples ◽  
Orthogonal Regression ◽  
Significant Difference ◽  
International Normalised Ratio ◽  
International Sensitivity Index

SummaryThe aim of this study was to determine whether the concentration of trisodium citrate used to anticoagulate blood has an effect on the INR of the sample and the ISI of the thromboplastin. Five thromboplastins including and Australian reference material were used to measure the prothrombin time of normal and patient samples collected into two concentrations of trisodium citrate - 109 mM and 129 mM. There was no effect of citrate concentration on the INRs determined with the reference material. However for the other four thromboplastins there was a significant difference between INRs for the two citrate groups. The prothrombin times of the samples collected into 129 mM were longer than those collected into 109 mM. This difference was only slight in normal plasma but more marked in patients receiving oral anticoagulants, causing the INRs for patient plasmas collected into 129 mM citrate to be higher then the corresponding samples collected into 109 mM citrate.From orthogonal regression of log prothrombin times by the reference method against each thromboplastin, we found that the ISI for each thromboplastin was approximately 10% lower when determined with samples collected into 129 mM citrate than with samples collected into 109 mM. These results suggest that the concentration of trisodium citrate used for collection of blood samples can affect the calculation of the INR and the calibration of the ISI of thromboplastin. This was found both for commercial thromboplastins prepared by tissue extraction and for a recombinant tissue factor.

In-house Calibration of the International Sensitivity Index or Calibration Curve for Determination of the International Normalized Ratio

2004 ◽  
Vol 128 (3) ◽  
pp. 308-312
Author(s):  
William F. Brien ◽  
Linda Crawford ◽  
Anne Raby ◽  
Harold Richardson
Keyword(s):  
Calibration Curve ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Improve Performance ◽  
Accuracy And Precision ◽  
The Stability ◽  
Method Of Assessment ◽  
International Sensitivity Index

Abstract Context.—The international normalized ratio (INR) has been used since 1983 to standardize prothrombin time results for patients on oral anticoagulants. However, significant interlaboratory variations have been noted. Attempts have been made to address these differences with the use of instrument-specific International Sensitivity Index (ISI) values and in-house calibration of ISI values. Objective.—To assess the performance of laboratories using a calibration curve for INR testing. Design.—Attempts to improve performance of the INR include the use of instrument-specific ISI values, model-specific ISI values, in-house calibration of ISI values, and more recently, the preparation of a calibration curve. Several studies have shown an improvement in performance using these procedures. In this study of licensed laboratories performing routine coagulation testing in the Province of Ontario, Canada, the determination of the INR by a calibration curve was compared with the laboratories' usual method of assessment. These methods were subsequently analyzed by comparing the results to instrument-specific ISI, model-specific ISI, and in-house calibrators. International normalized ratios derived by both methods were analyzed for accuracy and precision. The stability of a calibration curve was also investigated. Results.—Performance of INR testing has improved with use of a calibration curve or in-house calibrators. Conclusion.—The results confirm that either in-house calibrators or the calibration curve improve performance of INR testing. The calibration curve may be easier to use and appears stable up to 4 months.

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.

Are Capillary Whole Blood Coagulation Monitors Suitable for the Control of Oral Anticoagulant Treatment by the International Normalized Ratio?

1993 ◽  
Vol 70 (06) ◽  
pp. 0921-0924 ◽  
Author(s):  
Armando Tripodi ◽  
Arnaldo A Arbini ◽  
Veena Chantarangkul ◽  
Donato Bettega ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Whole Blood ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Regression Line ◽  
International Normalized Ratio ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Calibration Model ◽  
Oral Anticoagulant Treatment

SummaryThe 512 Coagulation Monitor is a portable coagulation photometer that uses disposable cartridges containing a lyophilized rabbit brain thromboplastin to measure the PT for capillary whole blood. It has been proposed as a suitable system for patient self monitoring at home, but its performance has never been thoroughly assessed for results expressed as International Normalized Ratio (INR). In particular, there is no available information about the adequacy of the WHO calibration model with the Monitor. The aims of the study were to determine the International Sensitivity Index (ISI) against the secondary International Reference Preparation for rabbit thromboplastin and to assess the precision of the INR. The study demonstrates that the Monitor can be calibrated with the WHO model, because log-transformed PTs for patients stabilized on oral anticoagulants and normal individuals are linearly related and because the same orthogonal regression line describes patient and normal data points adequately. However, the ISI calculated in this study (2.715) is higher than that adopted by the manufacturer (2.036). The between-assay reproducibility of the Monitor is acceptable (CV = 9.7%) with results expressed in seconds, but become unacceptably poor when the results are converted into INR (CV = 18.8%) because of the high ISI value of the thromboplastin used. We think that the Monitor might be suitable for monitoring oral anticoagulant therapy if the manufacturer would provide a more sensitive thromboplastin in the cartridges.

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.

scholarly journals Use of Lyophilized Calibrant Plasmas for Simplified International Normalized Ratio Determination with a Human Tissue Factor Thromboplastin Reagent Derived from Cultured Human Cells

2003 ◽  
Vol 49 (12) ◽  
pp. 2006-2011 ◽  
Author(s):  
Anton M H P van den Besselaar ◽  
Wim P M Houdijk
Keyword(s):  
Tissue Factor ◽  
Human Tissue ◽  
Oral Anticoagulants ◽  
Regression Line ◽  
Reference Method ◽  
International Normalized Ratio ◽  
Human Cells ◽  
Sensitivity Index ◽  
Cultured Human Cells ◽  
The Mean

Abstract 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. CPP was validated for Simplastin HTF, a new human tissue factor reagent derived from cultured human cells. CPP precision was assessed as the CV of the slope of the regression line. The accuracy of the CPP was determined by comparing the INR obtained with the CPP with that obtained with the established ISI-based reference method. INRs of the calibrants were assigned by different routes: by manufacturer (consensus labeling) or by use of Simplastin HTF or International Reference Preparations (IRPs; rTF/95 or RBT/90). Results: The mean CV of the CPP regression slope ranged from 1.0% (Simplastin HTF reagent-specific INR) to 2.4% (INR assigned with rTF/95). INRs calculated with the CPP were similar to those obtained with the reference method, but when the routes for assigning INRs to the calibrant plasmas were compared, the mean difference in INR between CPP and the reference method was smaller with Simplastin HTF reagent-specific values. In several (but not all) cases, this difference was significant (P &lt;0.05, t-test). Conclusion: CPP can be used for local INR determination, but better precision and accuracy are obtained with reagent-specific INRs compared with INR assignment by consensus labeling or IRP.

Validity of International Normalized Ratio in Expressing Prothrombin Times in Anticoagulated and Nonanticoagulated Patients

1996 ◽  
Vol 2 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Rasheed Alshameeri ◽  
Eberhard F. Mammen ◽  
Christa Paisley ◽  
Christine Perry
Keyword(s):  
Human Placenta ◽  
Oral Anticoagulant ◽  
High Sensitivity ◽  
International Normalized Ratio ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Normal Range ◽  
Normal Ranges ◽  
Highly Sensitive ◽  
International Sensitivity Index

We investigated the effect of four thrombo plastins with different International Sensitivity Index (ISI) values on prothrombin times (PTs), expressed as International Normalized Ratios (INRs), of 30 normal plasmas, 30 patients on stable oral anticoagulant (OA) therapy, and 30 patients with prolonged PTs for reasons other than OA therapy. Normal ranges became signifi cantly longer when three thromboplastins of rabbit brain origin were used—the lower the ISI, the wider the normal range. The human placenta-derived thromboplastin had a range similar to the values obtained with the most insen sitive rabbit reagent. Significantly different INR values were noted when normal plasmas and plasmas of patients with prolonged PTs not due to OA therapy were tested. This was not the case when specimens from patients on OAs were tested. When PT values from 212 consecutive ly selected patients were tested with the least sensitive rabbit reagent (ISI 2.477) and the most sensitive human placenta reagent (ISI 1.06), significantly more "abnor mal" PTs were identified with the high-sensitivity throm boplastin. The data indicate that special attention has to be paid to "normal" ranges when thromboplastins with low ISI replace less sensitive reagents, that INR should not be used to express PT in patients not on stable OA therapy, and that with the routine use of highly sensitive reagents (low ISI) more abnormal patients are identified.

Laboratory Reporting of the International Normalized Ratio: Progress and Problems

2007 ◽  
Vol 131 (11) ◽  
pp. 1641-1647
Author(s):  
John D. Olson ◽  
John T. Brandt ◽  
Wayne L. Chandler ◽  
Elizabeth M. Van Cott ◽  
Mark T. Cunningham ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Proficiency Testing ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Laboratory Practice ◽  
Consensus Conferences ◽  
Quality Of Patient Care ◽  
The Mean ◽  
International Sensitivity Index

Abstract Context.—The international normalized ratio (INR) is widely used to monitor oral anticoagulation and to evaluate patients with coagulation disorders. Objective.—To examine the variability of the performance and reporting of the INR and to evaluate laboratory calculation of the INR. Design.—Between 1993 and 2003, laboratories participating in proficiency testing were surveyed. Participants provided the international sensitivity index and the mean normal prothrombin time used to calculate the INR. The INR was calculated from the data provided and compared with the INR reported to determine if the calculation was correct. Results.—Survey data regarding the INR collected between 1993 and 2003 demonstrate an improvement in reporting, using appropriate anticoagulant, using lower international sensitivity index reagents, and matching international sensitivity index and prothrombin time method. The all-method coefficient of variation of the INR improved from 18% to 5.8%. Among 3813 laboratories studied in 2002 and 2003, 4.1% miscalculated INR. Of 29 laboratories that reported investigation of the INR miscalculation, 11 (38%) reported correcting an INR that was being reported in patient results and that this error was corrected as a result of the study. Since beginning grading of the INR calculation, miscalculation of the INR has fallen to less than 1%. Conclusions.—Recommendations for change in laboratory practice made by consensus conferences are implemented during the course of many years. Difficulty calculating the INR was documented, and both the calculation and the variability in the reporting of the INR showed improvement. Proficiency testing, when closely evaluated and acted on, can have a direct impact on the quality of patient care.

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