Prothrombin time (PT)

Performed by adding tissue thromboplastin from human or animal brains and calcium chloride to citrated plasma.

Testing: Blood is drawn into a test tube containing liquid sodium citrate, which acts as an anticoagulant by binding the calcium in a sample. 

The blood 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.

Plasma is placed into a measuring test tube, with an excess of calcium in a phospholipid suspension: reversing the effects of citrate and enabling the blood to clot again.

To activate the extrinsic / tissue factor clotting cascade pathway, tissue factor (also known as factor III) is added and the time the sample takes to clot is measured.

The prothrombin time ratio is the ratio of a subject’s measured prothrombin time in seconds to the normal laboratory reference PT. 

The prothrombin time is the time it takes plasma to clot after addition of tissue factor (obtained from rabbits, or recombinant tissue factor, or from brains of autopsy patients). 

The prothrombin time measures the quality of the extrinsic pathway as well as the common pathway of coagulation. 

The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. 

Factor VII has a short half-life and the carboxylation of its glutamate residues requires vitamin K. 

The prothrombin time can be prolonged as a result of deficiencies in vitamin K, warfarin therapy, malabsorption, or lack of intestinal colonization by bacteria.

Poor factor VII synthesis due to liver disease or increased consumption as in disseminated intravascular coagulation may prolong the PT.

The PT ratio has been replaced by the INR.

The result in seconds for a prothrombin time performed on a normal individual will vary according to the type of analytical system employed, due to the different types and batches of manufacturer’s tissue factor used in the reagent to perform the test. 

Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor that indicates how a particular batch of tissue factor compares to an international reference tissue factor. 

The ISI is usually between 0.94 and 1.4 for more sensitive and 2.0–3.0 for less sensitive thromboplastins.

The INR is the ratio of a patient’s prothrombin time to a normal sample, raised to the power of the ISI value for the analytical system being used.

The INR was devised to standardize the results. 

Because of variable sensitivities of thromboplastin significant differences in results required the development of INR to monitor warfarin therapy.

More sensitive to deficiencies of factor VII within the extrinsic pathway and less sensitive to deficiencies in the final common pathway (factors V, X II and fibrinogen).

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. 

An estimated 800 million PT/INR assays are performed annually worldwide.

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. 

With newer reagents a 1.5 times normal PT, 15.5s, reflects only mild and insignificant factor deficiencies.

The reference range for prothrombin time is usually around 12–13 seconds.

The INR in absence of anticoagulation therapy is 0.8–1.2.

The target range for INR in anticoagulant use (e.g. warfarin) is 2 to 3.

If more intense anticoagulation is thought to be required, the target range may be as high as 2.5–3.5 depending on the indication for anticoagulation.

Reflects plasma levels of extrinsic and common pathway coagulation pathway factors including, factors VII, V, X, prothrombin and fibrinogen.

Can be elevated when coagulation factor deficiency in common pathway of coagulation cascade is present and includes: fibrinogen, factor II, factor V or factor X.

A prolonged PT associated with liver disease or vitamin K deficiency , or both.

Frequency of protime measurement directly related to maintenance of therapeutic range for warfarin anticoagulation.

Measurement weekly associated with 77-85%% of patients expected to remain within the target range for warfarin anticoagulation.

The targeted  INR may be higher in particular situations: mechanical heart valve. 

A high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot.

Measurement monthly associated with 50-60% of patients expected to remain within the target range for warfarin anticoagulation.

Measurement every three days associated with 92%% of patients expected to remain within the target range for warfarin anticoagulation.

Theoretically heparin should prolong the PT by inhibiting thrombin in the final common pathway but this effect is overcome with the addition of heparin neutralizers such as Polybrene which can neutralize up to 2 U/ml of heparin.

In the presence of excessive heparin, as may be present after a heparin bolus, or drawing of blood from a heparin coated catheter, or drawing blood above the site of heparin infusion, may prolong the PT by overwhelming the heparin neutralizer.

A Lupus anticoagulant is a circulating inhibitor predisposing for thrombosis, that may skew PT results, depending on the assay used.

Variations between various thromboplastin preparations still exist.

The Fiix prothrombin time is used for  monitoring warfarin and other vitamin K antagonists.

The Fiix prothrombin time is only affected by reductions in factor II and/or factor X and this stabilizes the anticoagulant effect and appears to improve clinical outcome according to an investigator initiated randomized blinded clinical trial, The Fiix-trial.

Near-patient testing or home INR monitoring has the ability to deliver results close in accuracy to those of the lab.

A meta analysis of 14 trials showed that home testing led to a reduced incidence of bleeding and thrombosis and improved the time in the therapeutic range, which is an indirect measure of anticoagulant control.

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