Relationship Between PT and INR
The INR is a mathematically standardized transformation of the PT that corrects for variability between different thromboplastin reagents and instruments, calculated using the formula: INR = (PT patient / PT normal)^ISI, where ISI is the International Sensitivity Index of the thromboplastin reagent. 1
Mathematical Relationship
The PT measures the time in seconds for plasma to clot after adding thromboplastin reagent, while the INR converts this raw PT value into a standardized ratio that allows comparison across different laboratories and reagent systems 1
The conversion formula requires three components: the patient's PT in seconds, the mean normal PT (MNPT) from at least 20 healthy individuals, and the ISI value assigned to the specific thromboplastin reagent 1
The ISI represents the sensitivity of a commercial thromboplastin relative to an international reference standard, with values typically ranging from 0.9 to 2.0, where lower ISI values indicate reagents more similar to the reference standard 1
Clinical Purpose and Validation
The INR was specifically designed and validated only for monitoring patients on vitamin K antagonists (warfarin, coumarin derivatives) and should not be used as a general coagulopathy screen or bleeding predictor in non-VKA patients 2, 3, 4
The World Health Organization endorsed the INR system in 1983 to address the problem that PT results for the same patient varied dramatically between laboratories due to different thromboplastin sensitivities to VKA-induced coagulation defects 1
Without INR standardization, therapeutic ranges established in clinical trials could not be applied to individual patients, and dose adjustments would be unreliable 1
Key Technical Considerations
The relationship between PT and INR is logarithmic, not linear, meaning that as PT increases, INR rises exponentially rather than proportionally 1
Different PT methodologies exist (Quick-type using plain thromboplastin versus Owren-type using combined thromboplastin with added plasma), and each requires specific calibration approaches for accurate INR determination 5, 6
Local laboratory calibration using certified plasmas can reduce INR variability from +14.4% deviation to +1.04% compared to using manufacturer-provided ISI values alone 1
Common Pitfalls to Avoid
Never use INR to predict bleeding risk in patients not taking vitamin K antagonists—it has sensitivity under 50% for bleeding prediction and lacks biological plausibility in this context 2, 3
The INR only reflects depression of vitamin K-dependent factors (II, VII, X) and does not assess platelet function, fibrinogen, or factor XIII, making it an incomplete assessment of hemostasis 4
ISI values can vary even among instruments of the same model from the same manufacturer, so laboratories must verify or validate ISI values for their specific reagent-instrument combination rather than relying solely on manufacturer specifications 7, 8
In patients with lupus anticoagulant, the PT baseline is rarely prolonged (unlike aPTT) because PT reagents contain much higher phospholipid concentrations that neutralize lupus anticoagulant activity, though this varies by reagent 1