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.

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.

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.

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.

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

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.

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.

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

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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