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A brief discussion of prothrombin time

A brief discussion of Prothrombin Time

Measuring the efficacy of vitamin K antagonist therapy

Understanding prothrombin time and INR.

Prothrombin time

 

Prothrombin time (PT) is the primary method 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 X).1,2 Changes in the PT noted in the first few days of vitamin K antagonist (VKA) therapy are primarily due to reductions in factor VII which has the shortest half-life of 6 hours. The reduction of factors X and II subsequently contribute to prolongation of the PT. 2

Either venous or capillary blood can be used to monitor anticoagulation therapy. 2 To produce a result, thromboplastin is added to the blood sample to activate coagulation.2 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 PT. 2

International Sensitivity Index 

 

Thromboplastin reagent can be produced by a variety of methods, which results in varying responsiveness to a decrease in the vitamin K-dependent coagulation factors.3 To render coagulation times as comparable as possible, the World Health Organization (WHO) approved a standard reference thromboplastin in 1983.3 Every manufacturer of thromboplastin must calibrate his reagent against the WHO international reference preparation (IRP). The value obtained is known as the international sensitivity index (ISI).3

WHO recommends the ISI of thromboplastins to be between 0.9 and 1.7. 4 However, ISI’s towards the lower end of the scale are favorable.4

 

International normalized ratio

 

The ISI is used in the calculation of international normalized ratio (INR), which is a standardized reporting method developed to allow for comparability of INRs from different laboratories across the world. 3

The INR method is not perfect in correcting for differences between different laboratories utilizing different thromboplastin reagents, but it does reduce the variation and provides clinically useful results. To minimize this variation, each monitoring site should use results from only one type of instrument and thromboplastin reagent origin for each patient.

Calculation

 

INR = (Patient PT / Mean Normal PT) ^ISI

 

Mean normal PT is the geometric mean PT of about 20 healthy
subjects obtained via the blood-collections system and tested
with the same make and lot of thromboplastin as that of the ISI
in use. 3

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 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.

In the spotlight

  1. Hirsh et al. (2003). Circulation 107, 1692–1711
  2. Ageno et al. (2012). Chest 141 (Suppl):e44S–e88S
  3. Boroumand and Hamidreza. (2010). J Teh Univ Heart Ctr 2, 57-68
  4. World Health Organization. (2013). Technical report available from https://www.who.int/bloodproducts/publications/TRS_979_Annex_6.pdf?ua=1 [Accessed November 2019]