History of the Prothrombin Time and Development of the INR
Leon Poller
European Concerted Action on Anticoagulation
Mean results with different thromboplastins in 30 patients
Poller L. Acta Haemat. 32:292-298 (1964)
Mean doses of warfarin from different geographical locations.
Striped boxes indicate rabbit reagent.
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.
Figure 1 Figure 2
ACCP Consensus Meeting
An example of the orthogonal regression line
Calibration lines from the seventeen participant centres
The hierarchical structure of thromboplastin calibration
IRP = International Reference Preparation. *Now discontinued.
IRR = International Reference Reagent. IS = International Standard.
International reference preparations for thromboplastins 2003
INR = Prothrombin Ratio (PR)ISI
Causes of Erroneous INRs (1)
• Pretest variablesErroneous prothrombin ratio determination
Variations in manual techniqueCoagulometer 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.
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)
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.
Coagulometer Effects of ACL and MLA
The ISI of thromboplastins and effect of ISI on the width of therapeutic range in prothrombin ratios.
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
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-NC 536 2.91 2.52 +15.2
21.3
CoaguChek Mini
536 2.40 2.59 -7.1
Br Med J 2003;327:30-34
DAILY TELEGRAPH 23 SEPTEMBER 2003
Proportion of time in INR ranges
*INR results for all weeks, including first 3 weeks
Lancet 1998;352:1505-9
