Abstract
Laboratory monitoring of oral anticoagulants is mandatory to ensure efficacy and safety
of therapy. The test of choice is the prothrombin time (PT), using thromboplastins,
which vary markedly in respect of the defect induced by oral anticoagulants. Standardization
is improved by the use of the WHO calibration model for thromboplastins. This system
defines the International Sensitivity Index (ISI) of a reagent in relation to a reference
material. This is then used together with a locally determined mean normal PT to derive
the International Normalized Ratio (INR). There is an inverse relationship between
sensitivity and ISI, the lower the ISI the greater is the sensitivity of the reagent.
There are important practical advantages to using a sensitive reagent with ISI of
1.2 or less. The ISI system was originally designed for manual tests and in some cases
the ISI is influenced by the use of coagulometers, which generally have the effect
of lowering the ISI. For this reason the ISI should be assigned for the combination
of reagent and endpoint detection system. A thromboplastin should not be used with
techniques for which the ISI is unknown. In some instances there is variation between
instruments of the same type, in which case a local calibration using plasma calibrants
with assigned values can be considered. The precise requirements for such local calibrations
are presently the subject of research in a number of centers. The INR/ISI system is
increasingly being adopted in many countries for anticoagulant therapy. Some past
difficulties leading to discrepancies between results with different reagents have
now been resolved and the view that this is the best available system for standardization
of the PT for monitoring oral anticoagulants is widely held.
Keywords:
Oral anticoagulants - prothrombin time - standardization - INR - ISI
