Assessment of Different Mathematical Models for Calculating and Expressing the Results of Coagulation Test Procedures

Kahan, J; Norén, Ingrid

doi:10.1055/s-0038-1651411

Cited by 4 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the assumption of a straight line relationship through the origin of a PT ratio plot (as in Fig. 1) is an empirical one, it should occasion no surprise that exceptions to this pattern have been found (12,13,14). These exceptions have arisen generally in cases where thromboplastins of very different sensitivities have been compared and where the calibration constant has been markedly different from 1.…”

Section: The Need To Modify the Who Schemementioning

confidence: 99%

Calibration of Reference Thromboplastins and Standardisation of the Prothrombin Time Ratio

1983

View full text Add to dashboard Cite

SummaryThromboplastins vary in their sensitivity to the haemostatic defect induced by oral anticoagulants. To provide a means of standardising prothrombin time tests, the World Health Organization adopted in 1977 a scheme for calibrating thromboplastins in terms of an International Reference Preparation. Unfortunately, the model on which this scheme was based does not always hold. A revised calibration model has therefore been developed and this has been tested in a recent collaborative study. The revised model, which retains fundamentally the same principle for standardising prothrombin time tests, has proved suitable for calibrating thromboplastins of different species and types and, moreover, has certain statistical advantages over its predecessor. In September 1982, the WHO Expert Committee on Biological Standardization adopted the revised model. This paper explains the nature and rationale of this change and considers its practical implications.

show abstract

Section: The Need To Modify the Who Schemementioning

confidence: 99%

Calibration of Reference Thromboplastins and Standardisation of the Prothrombin Time Ratio

1983

View full text Add to dashboard Cite

show abstract

“…The effective standard error contains sufficient information on the interlaboratory variance, such that it can be used directly for the calculation of the coefficient of variation of INR estimates. In the example given above, the effective standard error of the ISI is 0.0956, and in comparison the marginal standard error is only se Standard error (of the mean) (46) SOP Standard Operating Procedure (36,44) TSR Thromboplastin Sensitivity Ratio (10) WHO World Health Organization…”

Section: Discussionmentioning

confidence: 99%

“…Kahan & Norén, in 1975 [36], calculated the coagulation activity, expressed as percentage of normal and as clotting time ratio, in 220 specimens from patients on OAT by three different thromboplastins (Thrombotest, Simplastin-A, and Normotest). They found that the "distribution of percentage values showed a fairly pronounced deviation from normality.…”

Section: Normalization Of Percentage Prothrombin By Logarithmic Trans...mentioning

confidence: 99%

“…Since the assumption of a straight line relationship through the origin of a PT ratio plot is an empirical one, it should occasion no surprise that exceptions to this pattern have been found [e.g. Kahan & Norén [36]]. These exceptions have arisen generally in cases where thromboplastins of very different sensitivities have been compared and where the calibration constant has been markedly different from 1.…”

Section: The International Normalized Ratio Kirkwood's Analysismentioning

confidence: 99%

See 1 more Smart Citation

Monitoring Oral Anticoagulant Therapy

Tripodi

2008

Quality in Laboratory Hemostasis and Thrombosis

View full text Add to dashboard Cite

Since 1984, when I was matriculated as a medical student, I have taken an interest in all the three major areas, but my main occupation in the past 12 years has been with the quantitative epistemological discipline of statistics, which deals with the collection, analysis, interpretation, and presentation of numerical data. The formal foundation for theoretical statistics is mathematical statistics, in which I took a master's degree (MSc) in 1995.Concurrently, in the past nine years, and especially since 1995, when I was first employed at the Department of Biostatistics, I have been occupied with biostatistics, which focuses on the development and use of statistical methods to solve problems and to answer questions that arise in human biology and medicine. My experience has been within various scientific disciplines including different medical specialties, and in every case I have found that knowledge of the subject matter of the particular area is an important prerequisite in order to be able to communicate with the specialist.A remarkable feature of many of the scientific problems I have encountered as a biostatistician is their similarity! It is striking, and fascinating, how different scientific areas have encountered the same epistemological challenges and how they independently have invented almost the same (good or bad) strategies for dealing with the analysis and interpretation of data. Another striking feature is the difference in language and traditions, which hinders the different areas in communicating their epistemological problems and discoveries to each other. With this in mind I consider it the principal goal of biostatistics to 1) collect epistemological and cognitive problems and solutions from different subject matter areas of research; 2) distill the problems and solutions through the language of mathematical statistics; 3) present, analyze and discuss the problems and solutions in a general setting within the mathematical-statistical scientific community; and 4) translate possible solutions to the problems to the language and traditions of the particular subject matter disciplines.A major challenge as a biostatistician is the translation of solutions and suggestions from very general terms to terms which are recognized by the subject matter specialist. I hope that this dissertation will be judged on the scientific usefulness of its applications of general statistical methodology, rather than on its exact compliance with the language and traditions of the subject matter disciplines, which it involves.

show abstract

“…[12] were among the first to consider these relations. They were followed by others [13–20] which in 1977 led to the postulation by WHO of a linear relationship between PT ratios from different thromboplastins [21]. In 1983, Kirkwood [22] suggested that the logarithms of PTs of different thromboplastins yields a linear relationship and also homogeneity of variance.…”

Section: The Mnpt Assumptionmentioning

confidence: 99%

Inaccuracy of international normalized ratio (INR) measurements and suggestions for improved WHO guidelines for calibration of reference preparations – a statistical study

Attermann

2003

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Numerous empirical studies show that the accuracy of international normalized ratio (INR) measurements is unsatisfactory and worse than generally expected. We demonstrate that a plausible reason for this large inaccuracy is a conventional calibration procedure of reference preparations with (i) an erroneous assumption that the line relating logarithmic prothrombin times (log PTs) of patients passes through the mean log PT of the 'normal' population (mean normal PT); (ii) non-perceived interactions between patients and PT systems; and (iii) systematic exclusions of 'outliers'. The same conventional procedure also results in serious overestimation of the accuracy of INR measurements, thus leading to a false sense of security in oral anticoagulant therapy. In an example with data from WHO guidelines, we show that the systematic overprediction of INR (which is believed to be 0) may be as large as 5%, when prediction is performed under the conventional WHO model. Under the same model the CV of the predicted vs. the true INR is believed to be only about 1% when it in reality is more than 4%. We suggest that the conventional calibration procedure is modified in order to reduce the twofold negative impact of lower true accuracy and overestimated reported accuracy on oral anticoagulant therapy and to allow for an unambiguous definition of true INR values. Keywords: accuracy, calibration, international normalized ratio (INR).The international normalized ratio (INR) is recommended by the World Health Organization (WHO) for reporting prothrombin time (PT) in patients on stable oral anticoagulant therapy [1,2]. However, reports on inconsistent INR measurements suggest that the accuracy of these are overestimated [3][4][5][6][7][8][9]. In a recent study [10], we found that for blood samples with true INR 2 and 4, the 95% prediction intervals for INR measurements obtained directly by the second generation international reference preparation (IRP) RBT/79 are 1.7-2.4, and 3.2-5.0, respectively. These intervals are large compared, e.g. with the therapeutic range of 2-3 for patients with mechanical heart valves. In routine use the prediction interval is even larger, since routine INR estimates are obtained by commercial thromboplastins which have had their international sensitivity index (ISI) assigned either by the use of plasma calibrators with INR determined against an IRP, or by successive calibrations against a house standard and an IRP. Moreover the inaccuracy of IRPs will generally increase with the distance from the primary IRP 67/40.The aim of the present study was to investigate how some critical statistical assumptions of the WHO guidelines [2] for calibration of international reference preparations or secondary standards affect the validity of INR measurements. The focus is on a single calibration exercise within a single laboratory, but the results may be further generalized to multicenter calibrations and serial calibrations. The results can be used to optimize future calibrations in order to maximize the va...

show abstract

Assessment of Different Mathematical Models for Calculating and Expressing the Results of Coagulation Test Procedures

Cited by 4 publications

References 0 publications

Calibration of Reference Thromboplastins and Standardisation of the Prothrombin Time Ratio

Calibration of Reference Thromboplastins and Standardisation of the Prothrombin Time Ratio

Monitoring Oral Anticoagulant Therapy

Inaccuracy of international normalized ratio (INR) measurements and suggestions for improved WHO guidelines for calibration of reference preparations – a statistical study

Contact Info

Product

Resources

About