“…An under-appreciated disadvantage of normalizing against NPP values is that different NPP preparations, or even different batches of the same preparation, do not necessarily generate the same clotting times with a given reagent, or with different reagents of the same test type [20,[76][77][78]. The greater the distance of the clotting time of a given NPP from the assay and analyser-specific reference interval (RI) mean clotting time, the greater the likelihood of systematic bias towards false-positive or false-negative ratios [20,74,77,78]. In that respect, in the same way that a locally derived, fixed geometric mean normal PT is used in the calculation of the international normalized ratio for VKA monitoring [79], a local reagent and analyser-specific RI mean clotting time is a viable alternative for the denominator in LA assay ratios [14,20,28,70,75,77,[80][81][82].…”