Historical Perspective:
After the discovery of coumadin in the 1920’s, it was found
that its effect on coagulation was reflected in elevated prothrombin
times (PT). The PT was first introduced by Armand Quick in 1935.
It wasn’t until the 1960’s that safe therapeutic ranges
were established by clinical studies...that range being a PT ratio
of "2-3 times normal". At that time, most thromboplastins
were prepared the same. As industry responded to the demand for
PT reagents, different sources and sensitivities of reagents emerged.
This occurred slowly and without realization by treating physicians.
Over the ensuing decades, reagents available gradually and subtly
then decreased in sensitivity. This resulted in shorter and shorter
normal prothrombin times (relative to what Quick’s original
reagent had produced, and on which the clinical trials had been
performed). Clinicians continued to adjust coumadin dosage based
on previous personal experiential data, expecting longer clotting
times. Some patients became over-anticoagulated, and increased
bleeding complications occurred. In 1977, an internationally standardized
thromboplastin reagent was created similar to the original used
by Quick. By 1980, essentially all lot numbers of PT reagents were
assigned an International Sensitivity Index (ISI). The ISI is then
used to calculate a ratio of patient PT to control PT which is
equivalent to the original studies. This standardized ratio is
the International Normalized Ratio (INR). The INR is meant to take
the place of "2-3 times normal". In other words, an INR
of 2.0 - 3.0 is equivalent to the original calculation of a prothrombin
time "2 - 3 times the control". Using the INR, oral anticoagulants
can be monitored the same literally throughout the world, regardless
of lab systems.
Practical Implications:
There is nothing inherently wrong with using the raw prothrombin
time to adjust coumadin therapy. However, laboratories periodically
acquire new instruments or change reagent manufacturers...which
changes may affect clotting times. They must also renew reagent
lots, and each lot number has its own unique ISI number. In other
words, to be precise in using the only the prothrombin time itself
(without any ratios), one would need to adjust the therapeutic
range each time these changes occur, even though the changes may
be small. The reported INR reflects the test reagent used in your
patient's test at the time of the test, and eliminates the need
for consideration of these changing lab instruments and reagents.
As stated in our reports, the INR is intended only for initial
and serial guidance in patients on oral anticoagulants. The
INR has not been generally accepted as a guidance for assessing
bleeding tendency or therapeutic reversal of elevated PT’s
in patients not receiving oral anticoagulants. An INR of 0.8-1.2
is equivalent to our normal range, and is taken to mean "No
Anticoagulant Effect Present".
Anticoagulation in the Midlands:
The following hospitals have, or will have within the year, the
same instrumentation and same reagents: LMC, PRMH, PBMC, Providence,
and VAH. This is an effort to further standardize monitoring in
our immediate community.
William R. Armstrong, MD, Dept. Pathology, LMC 2/17/03
[NOTE: Uncomplicated invasive procedures such as arteriography
and endarterectomy are probably unlikely to have bleeding complications
within the mildly anticoagulated zone of INR between 1.2 to 1.5.
Oozing due to coumadin effect is treated with fresh frozen plasma
(FFP)].
(posted February 20 2003; latest addition 24 Feb. 2003)
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