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Research Applied to Clinical Practice
by Robert C. Knies, RN MSN CEN
Section Editor
International Normalized Ratio (INR)
The traditional method of determining the efficacy of anticoagulation therapy is the prothrombin time (PT). This was first described by Armand J. Quick in 1935. He used thromboplastin derived from rabbit brains to prove his assumption that patients with bleeding abnormalities secondary to obstructive jaundice was due to a deficiency of prothrombin. This is now know to result from reduced levels of liver-produced vitamin K-dependent blood coagulation factors II, IX, and X (Florell & Rodgers, 1996).
Today a blood sample is collected in a tube containing citrated sodium, in the laboratory the sample is spun in a centrifuge, and a specific volume of thromboplastin reagent is added to the sample. The time until a fibrin clot forms, measured in seconds, is reported as the PT (Ortel, 1995). The thromboplastin reagent can be either an extract of mammalian tissue (lungs heart or brain of animals) rich in tissue factor, or a recombinant proportion of human tissue factor in combination with phospholipids (Hirsh & Poller, 1994).
Because thromboplastins are produced using different methods and from different sources, the sensitivity of an individual thromboplastin to another can vary greatly. The more sensitive the thromboplastin reagent the longer the resulting PT. Conversely, the less sensitive the reagent the shorter the resulting PT. Variance can even occur within a single batch depending on shelf time (Ortel, 1995). This variability in sensitivity and its effect on PT outcomes can have a major detrimental effects on the management of warfarin therapy in patients requiring anticoagulation. This variability has also caused great international debate and concern for several decades (Florell & Rodgers, 1996).
To help standardize this difference two formats were developed, the first was the International Sensitivity Index (ISI) and the second was the International Normalized Ratio (INR). The INR was developed to incorporate the ISI values and attempt to make PT results uniformly useable. The manufacturers assign an ISI to each batch of reagent after comparing each batch to a "working reference" reagent preparation. This "working reference" has been calibrated against internationally accepted standard reference preparations which have an ISI value of 1.0 (Ortel, 1995). By definition, the more sensitive thromboplastin have an ISI of less than 1.0 and the less sensitive are greater than 1.0. The ISI value is critical for calculation of the INR, because the ISI value is the exponent in the formula. Consequently, small errors in the ISI assignment may affect the calculated INR substantially (Florell & Rodgers, 1996).
To resolve the problem of highly variable PTs, the use of the INR has been recommended for monitoring patient's oral anticoagulant therapy. This recommendation is supported by the American College of Chest Physicians, the National Heart, Lung and Blood Institute and the British Society for Hematology (Nichols & Bowie, 1993).
It is important to emphasize that the INR is not a new laboratory test. It is simply a mathematical calculation that corrects for the variability in PT results attributable to the variable sensitivities (ISI) of the thromboplastin agents used by laboratories.
INR = - patient PT______ ISI |
OR |
INR = {PTR}ISI |
Mean normal PT |
PTR- is the prothrombin time ratio, which is the patient's observed PT (in seconds) divided by each laboratory's calculated mean normal PT (in seconds) (Ortel, 1995, Florell & Rodgers, 1996).
A target INR range of 2.0 to 3.0 is recommended
for most indications, such as treatment or prophylaxis of DVT, prevention of further
clotting in MI's and other preventive measures for patients with atrial fibrillation. An
INR of 2.5 to 3.5 is recommended for patients with prosthetic heart valves (Ortel,
1995).
Using the INR in other medical conditions, such as
coagulopathy or liver disease has not been deemed appropriate as of this time, because INR
was originally developed using anticoagulated patient populations. Despite its usefulness
during routine monitoring of warfarin therapy, the use of INR for monitoring during the
induction phase of therapy has not been fully supported (Hirsh & Poller, 1994).
Reliability is lost during the initial days of therapy because of the varying rates of
plasma clearance of vitamin K-dependent clotting factors. These factors are what the
thromboplastin reagents are sensitive to and in turn what the INR and PTR are actually
reporting. In addition, individual thromboplastin reagents vary in their sensitivities to
the vitamin K-dependent clotting factors (Ortel, 1995).
The INR system can be precise and valid when a sensitive
thromboplastin and manual method of clot detection are used. However, it loses precision
and accuracy when used to convert PT ratios obtained with less-sensitive thromboplastin
reagents or when automated clot detection systems are used. These problems can be avoided
by using reagents with low ISI's and proper calibration of machinery.
Although the INR system is far from perfect, it is the only practical solution currently available. With all of its faults, it is much better than an unadjusted PT system. Although the clinician would like a system with little or no variability, the goal is unattainable unless a standardized sensitive reagent is universally adopted.
References:
Florell, S.R. & Rodgers, G.M. (December,1996). The PT and the pendulum. American
Journal of Clinical Pathology, 699-700.
Hirsh, J. & Poller, L. (1994). International normalized ratio: A guide to
understanding and correcting its problems. Archives of Internal Medicine, 154, 282-288.
National Center for Health Statistics, Cypress, B.K. (September, 1984). Patterns of
ambulatory care in internal medicine. The National Ambulatory Care Survey, United States,
January 1980-December 1981. Vital and Health Statistics, Series 13, no. 80. DHHS Pub. No.
(PHS) 84-1741. Public Health Service. Washington D.C.: U.S. Government Printing Office.
Nichols, W. L. & Bowie, E. J. W. (1993). Standardization of the prothrombin time for
monitoring orally administered anticoagulant therapy with use of the international
normalized ration system. Mayo Clinical Procedure, 68, 897-898.
Ortel, L.B. (1995). International normalized ratio (INR); An improved way to monitor oral
anticoagulant therapy. Nurse Practitioner, 20 (9), 15-22.
"Research Applied to Clinical Practice: International Normalized Ratio
(INR)"
[http://ENW.org/Research-INR.htm]
is a webarticle by Robert C.
Knies, RN MSN CEN [bknies@stevenshealthcare.org]
©Robert C. Knies, RN MSN CEN
presented by Emergency Nursing World !
[http://ENW.org]
Tom Trimble, RN [Tom@ENW.org]
ENW Webmaster
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