Laboratory Monitoring of Warfarin Therapy - Pathology

Warfarin Monitoring
many environmental and dietary factors can
change the dose-response. Measuring the
prothrombin time (PT) remains the primary
mechanism by which warfarin anticoagulation
is monitored. Prolongation of
the PT, however, depends on the responsiveness
of the thromboplastin used to initiate
coagulation. Hence, the WHO has currently
established and international standard by
which manufacturers or individual labs can
determine an international sensitivity index
(ISI) for each lot of thromboplastin. A therapeutic
range of PT is then defined by the international
normalized ratio (INR), which is
the ratio between the patients PT to the mean
normal PT for the lab raised to the power of
the ISI:
Fig. 2. A nomogram for obtaining
an INR from a measured
prothrombin ratio (i.e., ratio of
patient PT/mean normal PT). The
ISI is provided by the manufacturer
of each lot of prothrombin
reagent (thromboplastin). In the
example shown, an INR of 3.0 is
obtained from a plasma sample
with a PTR of 2.0 if the ISI is 1.6.
INR = (Patient PT/Mean Normal PT) ISI
where the “mean normal PT” is the geometric
mean prothrombin time for the laboratory.
The ISI is a correction factor, specific for each
lot of laboratory prothrombin reagent, that
correlates the activity of the reagent to a
standard maintained by the World Health Organization.
A smaller ISI reflects a more sensitive
thromboplastin reagent such that a
more prolonged PT will be observed for the
same therapeutic effect.
In most medical institutions, the INR is
automatatically calculated by the laboratory
information system. The INR can also be calculated
from the above formula or derived
from an INR nomogram (Fig. 2).
The dosing of warfarin is driven by
monitoring the prothrombin time to achieve
a PT in the appropriate therapeutic range.
Typically 5 to 10 mg of warfarin is administered
daily with daily monitoring of the INR.
The dose is changed gradually until therapeutic
and then the INR is followed on a regular
but less frequent basis. Adjustments in dosage
should be based on the weekly dose since
Warfarin Monitoring 4