Do You Report an Accurate International Normalized Ratio?

Abstract and Introduction

Abstract

The current method for monitoring vitamin K antagonist (AVK) anticoagulant therapy is the international normalized ratio (INR) that provides consistency and standardization for the prothrombin time (PT) assay value. Even after the standardization of the INR, inaccuracies of this value have still been reported. To make the INR even more accurate, better local assessments of INR parameters are becoming available. These new methods use plasmas with certified INR values to locally verify and, if necessary, recalculate the international sensitivity index (ISI) for the local laboratory's reagent and instrument system. This CE Update will discuss the concepts of local verification and calibration to better define the manufacturer's assigned ISI value, thus reporting more accurate INR results.

Introduction

Our understanding of the basic science and clinical issues surrounding hemostasis has skyrocketed within the last 10 to 15 years. These advances have: 1) established better treatment for patients at risk for hemorrhage or thrombosis; 2) identified new hereditary coagulation disorders; and 3) provided mechanism(s) for clinical hemostatic diseases. With this in mind, clinicians have begun to put more demand on the coagulation laboratory. The laboratory has had to keep pace by developing new coagulation tests and better standardizing those tests already in use. The cornerstones of clinical coagulation testing are the prothrombin time and/or international normalized ratio (PT/INR) and the activated partial thromboplastin time (aPTT) for identifying and monitoring clinical coagulation disorders and therapeutics. Manufacturers have varied the sensitivities of these reagents to more easily assess this variety of clinical conditions. It now has become important for each laboratory to evaluate the commercial reagents to determine the most appropriate one for their clinical needs. The criteria for how reagents should be evaluated include: sensitivity for intended use, compatibility with instrumentation, number of assays performed each day, and cost.

In this CE Update, we discuss: 1) how to determine the INR; 2) how to locally verify and calibrate the PT reagent for more accurate INR values; and 3) the clinical use of the INR for monitoring anti-vitamin K anticoagulant therapy.

Cite this: Do You Report an Accurate International Normalized Ratio? - Medscape - Mar 01, 2011.

Table 1. Sources of Error in the Determination of the ISI Value
Source of Error
Comparison of Primary IRP to Secondary IRP Secondary IRP Comparison to PT Reagent Instrument/Reagent Compatibility Instrument Performance Environmental Conditions Technical Performance

Table 2. Reasons for the Necessity of Local Verification of the ISI and INR
Requirement	Reason
Required	When generic ISI is used for PT Reagent
	When PT Reagent and Instrument are not specified as a combination
	After any change of reagent or instrument
	New lot of PT Reagent
Recommended	When instrument-specific ISI is used for PT Reagent
	Major changes in Internal Quality Control without apparent cause
	Failure or near failure of Proficiency Testing without apparent cause
	After major instrument repair

Table 3. Example of Valid or Passed Verification of an ISI
		Plasma with Assigned INR of
		1.50	3.00	4.00
Run #1:	Replicate #1	1.52	3.04	3.98
	Replicate #2	1.51	3.12	3.81
Run #2	Replicate #1	1.48	3.08	3.91
	Replicate #2	1.50	3.11	3.92
Run #3	Replicate #1	1.49	3.09	3.89
	Replicate #2	1.48	3.14	3.87
Mean Value		1.50	3.10	3.90
Calculated Minimum (-15%)		1.28	2.55	3.40
Calculated Maximum (+15%)		1.73	3.45	4.60
PASSED/FAILED		PASS	PASS	PASS

Table 4. Example of Failed Verification of an ISI
		Plasma with Assigned INR of
		1.50	3.00	4.00
Run #1	Replicate #1	1.55	3.24	4.88
	Replicate #2	1.52	3.12	4.35
Run #2	Replicate #1	1.49	3.28	4.58
	Replicate #2	1.50	3.17	4.77
Run #2	Replicate #1	1.51	3.40	4.65
	Replicate #2	1.52	3.18	4.50
Mean Value		1.52	3.23	4.62
Calculated Minimum (-15%)		1.28	2.55	3.40
Calculated Maximum (+15%)		1.73	3.45	4.60
PASSED/FAILED		PASS	PASS	FAIL

Table 5. Example of Calibration Data of the Local ISI
	Plasma with Assigned PT Values
	11.2	23.1	31.9	42.8
Run #1 Replicate #	11.3	23.2	32.4	43.5
Replicate #2	11.2	23.5	31.4	41
Run #2 Replicate #1	11.1	22.8	32.1	40.2
Replicate #2	11.1	23.1	31	42.6
Run #3 Replicate #1	11.2	22.6	32.4	43.8
Replicate #2	11.3	23	31.4	41.8
Mean Value	11.2	23.0	31.8	42.2
%CV	0.80%	1.37%	1.9%	2.98%

See Figure 3 for the orthogonal regression graph and the calculations of local ISI.

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Do You Report an Accurate International Normalized Ratio?

Find Out Using Local Verification and Calibration

Abstract and Introduction

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