INR (International normalized ratio)
The international normalized ratio (INR), prothrombin ratio (PR) and
prothrombin time (PT) are measures of the extrinsic pathway of
coagulation. They are used in the measure of warfarin dosage, liver
damage and vitamin K status. The reference range for prothrombin time
is 7-10 seconds, the range for the INR is 0.8-1.2.
The prothrombin time is the time it takes plasma to clot after
addition of tissue factor (obtained from animals). This measures the
quality of the extrinsic pathway (as well as the common pathway) of
The speed of the extrinsic pathway is very affected by levels of
factor VII in the body. Factor VII has a short half-life and its
synthesis requires vitamin K. Deficiencies in vitamin K, which can be
caused by warfarin, liver damage, or an immature liver in newborns,
result in an increased prothrombin time.
Measurement of prothrombin time
The prothrombin time can be measured roughly on whole blood, (which is
done in neonates), but is more commonly measured from blood plasma.
Blood is taken into a vacutainer containing liquid citrate. Citrate
acts as an anticoagulant by using up all the calcium in a sample. The
blood is mixed, then centrifuged to separate blood cells from plasma.
The plasma is put through a coagulation machine, which takes a sample
of the plasma. An excess of calcium is added, which enables the blood
to clot again. Tissue factor (or thromboplastin) is added, and and the
time the sample takes to clot is measured optically.
The prothrombin ratio is the prothrombin time for a patient, divided
by the result for control plasma.
International normalized ratio
Because of differences between different batches and manufacturers of
tissue factor (it is a biologically obtained product), the INR was
devised to standardise the results.
Each manufacturer gives an ISI (International Sensitivity Index) for
any tissue factor they make. This ISI says how their tissue factor
compares to other company's.
The INR is the ratio of a patient prothrombin time to a normal
(control) sample, raised to the power of the ISI.
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