NPM & INR Calculation Guidelines
Normal Patient Mean (NPM) — Geometric Mean of PT
The NPM is calculated as the geometric mean of all valid PT values. The geometric mean is used rather than the arithmetic mean because PT values from a normal population are approximately log-normally distributed — the geometric mean is more resistant to the influence of extreme values and better represents the central tendency of the distribution.
Normal Patient Mean (NPM)
NPM = exp( [ln(PT₁) + ln(PT₂) + … + ln(PTₙ)] / n )
Equivalently: the nth root of the product of all PT values. Computed by taking the natural log of each PT value, averaging the logs, then exponentiating the result. Maintains full floating-point precision for use as the INR denominator.
INR Calculation
Once the NPM is established, INR values are computed for each normal subject using the standard WHO INR formula. The International Sensitivity Index (ISI) is a reagent lot–specific calibration constant published by the reagent manufacturer. It characterizes how sensitive the reagent is relative to the WHO International Reference Preparation — an ISI of 1.0 indicates identical sensitivity.
INR
INR = (PT / NPM)^ISI
Where PT is the patient's (or normal subject's) raw Prothrombin Time in seconds, NPM is the Normal Patient Mean established from the current reagent lot on this instrument, and ISI is the International Sensitivity Index from the reagent lot's package insert. By definition, a normal subject measured at exactly the NPM will have INR = 1.0.