A brief discussion of Prothrombin Time

Prothrombin time and international normalised ratio are the parameters used to measure the efficacy of oral anticoagulation therapy.

Prothrombin Time (PT)

Prothrombin time (PT) is the primary assay used in monitoring oral anticoagulant therapy. The prolongation of PT depends on reductions in three of the vitamin K dependent clotting factors (II, VII and IX). Changes in the PT noted in the first few days of warfarin therapy are primarily due to reductions in factors VII and IX, which have the shortest half-lives (six and 24 hours, respectively).

Either venous or capillary blood can be used to monitor anticoagulation therapy.

To produce a result, thromboplastin is added to the blood sample to activate coagulation. This causes a blood clot to form. The time it takes for this clot to form is measured in seconds and is known as the prothrombin time (PT).

In most countries, blood coagulability is typically expressed in a unit known as the Quick value. In this case the measured prothrombin time is expressed in relation to the coagulation time of a healthy person. The value obtained is the "percentage of the standard value". In a person not receiving oral anticoagulation the "normal" Quick value is between 70 and 100%.

A Quick value of only 30%, for instance, indicates that the blood coagulation time is longer than normal.

The longer the patient's coagulation time, the lower the Quick value.

International Sensitivity Index (ISI)

Quick values measured with different thromboplastins cannot be directly compared with one another, as for instance sensitivity to clotting factors may differ. To render coagulation times as comparable as possible, the World Health Organization (WHO) approved in 1983 a standard reference thromboplastin. Every manufacturer of thromboplastin must calibrate his reagent against the WHO standard (2 references exist: one for human recombinant based thromboplastins, one for rabbit brain based ones). The value obtained is known as the International Sensitivity Index (ISI). This enables the various sensitivities of the thromboplastins to be ascertained and it will be used to calculate the INR.

WHO recommends ISI to be < 1.7. In many countries, a low (1.0) ISI is favored.

International Normalised Ratio (INR)

The INR is a standardization method that attempts to minimize differences between thromboplastin reagents through a calibration process in which all commercial thromboplastins are compared with an International Reference Preparation (IRP) maintained by the World Health Organization (WHO).

The INR method is not perfect in correcting for differences between different laboratories utilizing different thromboplastin reagents but it does reduce the variation between different laboratories and provides clinically useful results.

INR should only be used for patients on stable anticoagulation therapy.

Calculation

INR Calculation

MNPT (mean normal PT) is the geometric mean PT of minimum 20 healthy subjects in a defined laboratory population.

For example: The PT of a patient receiving oral anticoagulant is 64 seconds (= 18% Quick). The prothrombin time of a normal plasma is 22 seconds (= 100% Quick). The ISI of the thromboplastin used is 0.93. Substituting this value in the formula above gives the following INR:

(64) / (22) 0.93 = 2.7 INR

This signifies a coagulation time that is 2.7 times longer than the standard.

The longer the patient's coagulation time, the higher the INR.


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References

1. Lutze G. Useful facts about coagulation. Mannheim: Roche Diagnostics GmbH, 2000. (data on file)
2. Wagner C, Dati F. Thromboplastinzeit (german article). In: Thomas L, ed. Labor und Diagnose: TH-Books Verlagsgesellschaft, 2000; 613-616.
3. 
Tripodi, A. et al. (2003). Oral Anticoagulant Monitoring by Laboratory or Near-Patient-Testing: What a Clinician Should Be Aware Of. Seminars in Vascular Medicine, Volume 3, Number 3.http://www.medscape.com/infosite/pointofcaretesting/article-5#1