A PT ratio is obtained by dividing the patient PT in
seconds by the “mean of the normal range” (MNPT). This
ratio is then “normalized” by raising the results to the
power of the ISI of the PT reagent used. Lower the ISI of
the reagent used, closer will be the INR to the observed PT
ratio. Ideally, when the ISI of the reagent is 1.0 then the INR
is a simple PT ratio since (R)1.0 = R.
Currently many coagulation instruments are available
that can perform this exponential calculation by entering
the ISI of the reagent in use. Alternatively a table is provided
by reagent manufacturers for reading off “INR” directly for
the given patient PT ratio, corresponding to the ISI value of
Recommended Therapeutic Ranges for Oral Anticoagulant Therapy
• Prophylaxis of venous thrombosis
• Treatment of venous thrombosis
• Treatment of pulmonary embolism
• Prevention of systemic embolism
(to prevent systemic embolism)
• Mechanical prosthetic values
infarction recurrent 2.5-3.5 High
Clinical Hematology: Bleeding Disorders 291
R 1.00 1.05 1.10 1.15 1.20 1.25 1.29
1.0 1.00 1.00 1.10 1.00 1.00 1.00 1.00
1.1 1.10 1.11 1.11 1.12 1.12 1.13 1.13
1.2 1.20 1.21 1.22 1.23 1.24 1.26 1.27
1.3 1.30 1.32 1.33 1.35 1.37 1.39 1.40
1.4 1.40 1.42 1.45 1.47 1.50 1.52 1.54
1.5 1.50 1.53 1.56 1.59 1.63 1.66 1.69
1.6 1.60 1.64 1.68 1.72 1.76 1.80 1.83
1.7 1.70 1.75 1.79 1.84 1.89 1.94 1.98
1.8 1.80 1.85 1.91 1.97 2.02 2.08 2.13
1.9 1.90 1.96 2.03 2.09 2.16 2.23 2.29
2.0 2.00 2.07 2.14 2.22 2.30 2.38 2.45
2.1 2.10 2.18 2.26 2.35 2.44 2.53 2.60
2.2 2.20 2.29 2.38 2.48 2.58 2.68 2.77
2.3 2.30 2.40 2.50 2.61 2.72 2.83 2.93
2.4 2.40 2.51 2.62 2.74 2.86 2.99 3.09
2.5 2.50 2.62 2.74 2.87 3.00 3.14 3.26
2.6 2.60 2.73 2.86 3.00 3.15 3.30 3.43
2.7 2.70 2.84 2.98 3.13 3.29 3.46 3.60
2.8 2.80 2.95 3.10 3.27 3.44 3.62 3.77
2.9 2.90 3.06 3.23 3.40 3.59 3.78 3.95
3.0 3.00 3.17 3.35 3.54 3.74 3.95 4.13
3.1 3.10 3.28 3.47 3.67 3.89 4.11 4.30
3.2 3.20 3.39 3.59 3.81 4.04 4.28 4.48
3.3 3.30 3.50 3.72 3.95 4.19 4.45 4.67
3.4 3.40 3.61 3.84 4.09 4.34 4.62 4.85
3.5 3.50 3.73 3.97 4.22 4.50 4.79 5.03
3.6 3.60 3.84 4.09 4.36 4.65 4.96 5.22
3.7 3.70 3.95 4.22 4.50 4.81 5.13 5.41
3.8 3.80 4.06 4.34 4.64 4.96 5.31 5.60
3.9 3.90 4.17 4.47 4.78 5.12 5.48 5.79
4.0 4.00 4.29 4.59 4.92 5.28 5.66 5.98
4.1 4.10 4.40 4.72 5.07 5.44 5.83 6.17
4.2 4.20 4.51 4.85 5.21 5.60 6.01 6.37
4.3 4.30 4.63 4.98 5.35 5.76 6.19 6.58
4.4 4.40 4.74 5.10 5.50 5.92 6.37 6.76
4.5 4.50 4.85 5.23 5.64 6.08 6.65 6.96
4.6 4.60 4.96 5.36 5.78 6.24 6.74 7.16
4.7 4.70 5.03 5.49 5.93 6.40 6.92 7.36
4.8 4.80 5.19 5.62 6.07 6.57 7.10 7.56
4.9 4.90 5.31 5.74 6.22 6.73 7.29 7.77
5.0 5.00 5.42 5.87 6.37 6.90 7.48 7.97
5.1 5.10 5.53 6.00 6.51 7.06 7.66 8.18
5.2 5.20 5.65 6.13 6.66 7.23 7.85 8.39
5.3 5.30 5.76 6.26 6.81 7.40 8.04 8.60
5.4 5.40 5.88 6.39 6.95 7.57 8.23 8.81
5.5 5.50 5.99 6.52 7.10 7.73 8.42 9.02
5.6 5.60 6.10 6.65 7.25 7.90 8.61 9.23
5.7 5.70 6.22 6.78 7.40 8.07 8.81 9.44
5.8 5.80 6.33 6.91 7.55 8.24 9.00 9.66
5.9 5.90 6.45 7.05 7.70 8.41 9.20 9.87
6.0 6.00 6.56 7.18 7.85 8.59 9.39 10.09
Other Factors Influencing the INR
The variability in the responsiveness of the PT reagents,
is corrected through the “ISI” calibration, however, three
additional technical factors influence the INR:
¾ Magnitude of difference in the ISI value of test
thromboplastin and IRP (ISI=1.0)
¾ Method of clot detection employed during PT test.
MNPT is a critical requirement in the derivation of INR.
Ideally each laboratory must derive its own MNPT from
20 or more normal patients for a given PT reagent and lot
under use. This corrects within laboratory test variables
that influence PT results. If “normal control plasmas”
are used in place of patient plasma for arriving at the
MNPT it can effect the evaluation of the patients level of
Reagent ISI=2.5 Test Day 1 Test Day 2 Test Day 3
If the control time is greater than the mean normal
range (MNPT), the PT ratio for any patient PT will be
smaller, potentially leading to over coagulation. If the
control time is lesser than MNPT the ratio for any patient
PT will be greater, leading to under coagulation.
On the other hand MNPT for a particular laboratory
using the same combination of methodology, reagent and
instrument would remain constant.
ISI Value of PT Used and Method of Clot Detection
INR loses some precision when comparisons are made
with thromboplastins with markedly different ISI values
as against the IRP (ISI=1.0) and different methods of clot
detection, e.g. manual, mechanical, optical, etc.
Therefore, manufacturers must provide ISI values
adapted to the method used for clot detection. Also the
reagent used for reporting results should be ideally as
¾ Major advantage of the INR system is that it helps
alleviate confusion in the interpretation of PT
results. Usually laboratory changes like change in
thromboplastin and/or equipments could go unnoticed
¾ INR system affords comparison of PT results between
¾ INR system provides a more accurate and convenient
mean of monitoring patients who travel extensively.
¾ INR therapeutic ranges for different clinical conditions
are based on international collaborative studies. Usage
of standardized dosage reduces the risk of thrombotic
episodes or secondary bleeding.
Disadvantages of the INR System
¾ The prothrombin time test is always a part of the
preoperative screening panels. It is also frequently used
to evaluate other hemostatic disorders, such as liver
disease, DIC, LA, hereditary factor deficiencies and
acquired vitamin K deficiency. Since these disorders
have been excluded from the derivation of the ISI,
INR has a diagnostic and therapeutic value mainly
applicable for patients stabilized on oral anticoagulants.
Therefore, laboratories may prefer to report both the
INR and patients time in seconds depending on clinical
¾ The INR systems effectiveness would still depend on
the calibration of the coagulation instruments as well as
¾ Derivation of the correct MNPT and use of the mean
normal range in each laboratory.
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