Prothrombin time

The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the extrinsic pathway and common pathway of coagulation. This blood test is also called protime INR and PT/INR. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prower factor).

Prothrombin time

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PT is often used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway and common pathway of coagulation.

Blood is drawn into a containing liquid sodium citrate, which acts as an anticoagulant by binding the calcium in a sample. The blood is mixed, then centrifuged to separate blood cells from plasma (as prothrombin time is most commonly measured using blood plasma). In newborns, a capillary whole blood specimen is used.^[2]

test tube

A sample of the plasma is extracted from the test tube and placed into a measuring test tube (Note: for an accurate measurement, the ratio of blood to citrate needs to be fixed and should be labeled on the side of the measuring test tube by the manufacturing company; many laboratories will not perform the assay if the tube is underfilled and contains a relatively high concentration of citrate—the standardized dilution of 1 part anticoagulant to 9 parts whole blood is no longer valid).

Next an excess of (in a phospholipid suspension) is added to the test tube, thereby reversing the effects of citrate and enabling the blood to clot again.

calcium

Finally, in order to activate the extrinsic / tissue factor clotting cascade pathway, (also known as factor III) is added and the time the sample takes to clot is measured optically. Some laboratories use a mechanical measurement, which eliminates interferences from lipemic and icteric samples.

tissue factor

Statistics[edit]

An estimated 800 million PT/INR assays are performed annually worldwide.^[13]

History[edit]

The prothrombin time was developed by Armand J. Quick and colleagues in 1935,^[22] and a second method was published by Paul Owren,^[23] also called the "p and p" or "prothrombin and proconvertin" method. It aided in the identification of the anticoagulants dicumarol and warfarin,^[24] and was used subsequently as a measure of activity for warfarin when used therapeutically.

The INR was invented in the early 1980s by Tom Kirkwood working at the UK National Institute for Biological Standards and Control (and subsequently at the UK National Institute for Medical Research) to provide a consistent way of expressing the prothrombin time ratio, which had previously suffered from a large degree of variation between centres using different reagents. The INR was coupled to Dr Kirkwood's simultaneous invention of the International Sensitivity Index (ISI), which provided the means to calibrate different batches of thromboplastins to an international standard.^[25] The INR became widely accepted worldwide, especially after endorsement by the World Health Organization.^[26]

Prothrombin time