Abstract
Although the landscape of anticoagulation therapy is evolving, vitamin K antagonists
(VKAs) such as warfarin remain an anticoagulant of choice for many clinicians and
their patients. Nevertheless, management of VKA therapy remains challenging, largely
because of patient variability and drug and food interactions; thus, VKA dosing has
to be personalized. This is achieved by regular monitoring using a test called the
prothrombin time (PT) , mathematically converted to an international normalized ratio (INR). The INR system
is meant to harmonize laboratory test results by taking into account reagent and instrumentation
variability that is otherwise expected to give rise to variable PT values, but which
should accordingly lead to less variable INR values. Of clinical importance, too low
an INR is suggestive of increased thrombotic risk and typically means the VKA dose
should be increased, whereas too high an INR is suggestive of increased bleeding risk
and typically means the VKA dose should be temporarily withheld and/or decreased.
However, evidence continues to show that variability in INR values between laboratories
remains unacceptably high. Given that modern instrumentation provides for robust analytical
values—meaning highly reproducible intralaboratory clotting times or PTs in this case—the
most likely cause of high INR variability is inconsistency in the INR test components—meaning
the MNPT (mean normal PT) and ISI (international sensitivity index) values used by
laboratories to generate a given INR. In other words, there are doubts as to the accuracy
of some INR values because there are corresponding doubts about the accuracy of MNPT
and/or ISI values that have been assigned by some laboratories for their reagent/instrument
combination. The current report is intended to provide some solutions around the problems
of inaccurate INRs, ISIs, and MNPTs, thus aiming to drive laboratory INRs closer to
“truth,” and thus promote better patient management. The novel strategies include
a primary process of transference to obtain/verify MNPT and/or ISI values for a new
reagent using an existing reagent as reference, and a secondary process whereby external
quality assessment data can be used to correct bias or existing errors in assigned
MNPT and/or ISI values.
Keywords international normalized ratio - mean normal prothrombin time - international sensitivity
index
