1. History of the Prothrombin Time and Development of the INR Leon Poller European Concerted Action on Anticoagulation

2. Mean results with different thromboplastins in 30 patients Poller L. Acta Haemat. 32:292-298 (1964)

3. Mean doses of warfarin from different geographical locations. Striped boxes indicate rabbit reagent.

4. Bleeding events with Simplastin (ISI 2.5) and Manchester Reagent (ISI 1.0) control. Hull et al (1982). Prothrombin Ratio 2.0 Simplastin = 4.7 INR.

7. Figure 1 Figure 2

10. ACCP Consensus Meeting

11. An example of the orthogonal regression line

12. Calibration lines from the seventeen participant centres

13. The hierarchical structure of thromboplastin calibration

14. IRP = International Reference Preparation. *Now discontinued. IRR = International Reference Reagent. IS = International Standard. International reference preparations for thromboplastins 2003

15. INR = Prothrombin Ratio (PR) ISI

16. Causes of Erroneous INRs (1) Pretest variables Erroneous prothrombin ratio determination Variations in manual technique Coagulometer effects Incorrect normal value due to: Failure to use MNPT Error in MNPT due to: (a) unrepresentative selection; (b) technical faults; (c) non-use of geometric mean.

17. Causes of Erroneous INRs (2) Incorrect ISI calibration Drift of ISI Poor distribution of coumarin test samples, inadequate numbers of test samples Incorrect choice of IRP Incorrect transformation of PR to INR ‘Rogue’ plasmas (outliers)

18. Errors in PT Determination Pretest variables blood collection citrate container storage time temperature evacuated and non-evaculated tubes variations in manual technique coagulometers The overall trend of coagulometers is to accelerate the normal PT with the PR distorted. System-related ISI of limited value.

19. Coagulometer Effects of ACL and MLA

20. The ISI of thromboplastins and effect of ISI on the width of therapeutic range in prothrombin ratios.

21. Percentage deviation of mean INR from the IRP value with various thromboplastin reagents during the induction phase Reagent C Reagent B Reagent A Reagent D

26. Reliability of monitor INR on CoaguChek Mini and TAS PT-NC at 10 centres No. of samples Displayed INR “true” INR % difference Mean displayed INR difference TAS PT-NC5362.912.52 +15.2 21.3 CoaguChek Mini 5362.402.59 -7.1 Br Med J 2003;327:30-34

27. DAILY TELEGRAPH 23 SEPTEMBER 2003

28. Proportion of time in INR ranges *INR results for all weeks, including first 3 weeks Lancet 1998;352:1505-9