Establishment of a Reference Measurement System

Oral anticoagulant therapy with vitamin K antagonists (VKA) must be monitored in each patient with a laboratory test of the coagulant activity of the patient’s blood. Among all laboratory tests, the prothrombin time (PT), i.e. the tissue factor-induced coagulation time is the most used. However, many different reagents and techniques are applied for this test causing that the PT is expressed in many different ways. This led to serious misconceptions with respect to the optimal therapeutic range for VKA treatment.

Introduction of the Calibration model and Point-of-care testing (POCT)

Introduction Calibration model
Thromboplastins vary in their sensitivity (i.e. response) to the coagulation defect by VKA.
To provide means of standardizing PT tests, the World health Organization adopted a revised model for calibrating thromboplastins in terms of an International Reference Preparation (IRP). In this model thromboplastin’s calibration line slope was defined as the International  Sensitivity Index (ISI). A patient’s INR could be calculated with the equation: INR= (PT/MNPT)ISI in which MNPT is denote the Mean Normal PT. 

Introduction Point-of-care INR testing
Point-of-care (POC) procedures have been developed for INR testing that need less technical expertise because they use unmeasured whole blood samples and may be used by patients for self-testing. Accuracy, precision and stability of POC systems for INR testing have been assessed in a series of studies.

Today many patients treated with VKA use POC systems for self-testing and self-management. 

Uncertainty of the INR
The use of the INR enables comparisons to be made between results obtained with different thromboplastins and methods. It is a misconception that for an individual patient’s plasma the INR will always be identical with different thromboplastins and methods.
Different thromboplastins vary greatly in their responsiveness to individual vitamin K dependent clotting factors, as well as to some non-vitamin K dependent factors. Discrepancies between INRs determined with different thromboplastins arising from these biological variations and from additional technical errors are therefore not unexpected. Studies in individual patients who were monitored with two different PT reagents for several months, showed that there could be consistent INR differences between the reagents amounting to approximately 0.5 INR