Saturday, June 1, 2013

What is the INR Calculation - What should a Coumadin Patient know

What does INR mean and why should patients trust this test result
While the Prothrombin Time (PT) test was developed in 1935, the INR value was developed in early 1980's.  The need to standardize the PT test result so that coumadin dosing could be done with accuracy and confidence by health care providers was most important. Most patients on coumadin oral anti-coagulent therapy are familiar with the terms PT or Prothrombin Time and INR but very few understand the concept of why the INR is so important and critical to the dosing of this important plant derived medication.

Prothrombin Time tests are performed in clinical laboratories all across the globe on sophisticated laboratory analyzers or in the point of care setting using a small device the size of a tablet computer.
The test was developed with the use of purified biological material made from the brain tissue of rabbits. As technology and manufacturing practices evolved, Prothrombin Complex reagent production was developed with recombinant manufacturing methods without sacrificing the bunnies. Yeh! In early years before INR, the PT result was expressed in several variations to give the physician a better idea of the anti-coagulent effect of coumadin on his patient. The PT result was reported with a normal range which represented normal for the non-anticoagulated patient, other expressions of the PT result also combined a ratio value of test PT to Normal control, and also an established normal range ratio. However, due to variances in the many different test methods, reagents available, and sometimes technique of the person performing the test, the patients were at great risk of being over medicated or worse under medicated and even worse still overdosed. Hence the INR value was developed to provide the physician with a stable and reliable test result that was safe to use to dose patients with coumadin. Eventually, the WHO would get involved in the process of developing standards used to this day for manufacturing reagents, assigning a numerical value to the reagents [talk about this later] and test procedures.

INR stands for International Normalized Ratio which is a test result reported from the mathematical calculation of three parameters; PT result, Geometric Mean of the Normal PT, and ISI value of the reagent used. Ok I know – not another acronym!

ISI stands for International Sensitivity Index. This is the crucial component that makes for reliable INR results for all patients no matter what lab or device performs the PT test. The ISI value of every reagent manufactured for coagulation testing is assigned to that reagent based upon comparison of performance characteristics set up by WHO ~ World Health Organization. The ISI is much like the Octane rating of gasoline. The octane rating is the product of a calculation provided to consumers to assure gasoline meets certain performance standards. ISI is much the same thing. Reagents of different ISI values perform differently depending on the instrument system and the coag status of the patient; meaning deficiencies of coag factors, medications ingested, and testing conditions. Generally, the lower the ISI value of a reagent the more sensitive the reagent is to coag deficiencies which indirectly reflects effects of coumadin therapy.

The INR calculation is a brilliant mathematical process that helps to standardize a result used to directly adjust dosing of oral anti-coagulent. No matter where the specimen is analyzed, if laboratories follow procedures correctly the same blood sample can test very accurately between different Labs.

Here is the calculation:

How does this all work?
  • Coagulation Reagent manufacturers produce lots of Prothrombin Time reagent with a posted certified ISI rating.
  • Laboratories purchase this reagent for use with the laboratory instrumentation used for coagulation testing.
  • After validation testing including quality control, lot to lot comparison, and geometric mean calculation, the ISI value and geometric mean value is entered into the instrumentation data base for the INR calculation process.
  • Patient specimens are tested on the instrument for Prothrombin time which is measured in seconds.
  • The instrument automatically calculates the INR with the 3 components of the calculation.
  • The Prothrombin time result and INR calculated result are transmitted or entered into the laboratory computer system or otherwise given to the physician.
  • Patients on coumadin therapy must be evaluated by their physician for along with the PT and INR value to regulate the correct dose of coumadin for each patient.
With the advances in electronics, robotics, automation, and technology in the clinical laboratory along with a laboratories own Quality Assurance program to monitor the assay performance, the INR test result has become a reliable standard to monitor anti-coagulent therapy for the patient.

If you are a patient undergoing anti-coagulent therapy, or just frequent trips to a laboratory for monitoring testing contact the laboratory directly to ask to tour the facility.  You can gain assurance and confidence in your test results provided to your doctor for your care and treatments.  Laboratorians love to show off their labs, their work, and talk about the quality systems built into their laboratory to assure quality and accurate data for their patients. 

Scott Mayorga  MT(ASCP)H
Clinical Laboratory Scientist
Medical Technologist
LIS Manager



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