Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        Coagulation & thrombosis evaluation & about the Pro Time INR

Prothrombin Time INR

Oral Anti-coagulants and the INR

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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