Prothrombin Time and International Normalized Ratio or PT/INR

Prothrombin time or PT test is a blood test that is used to measure the time it takes for blood to clot. The results of this test can be expressed in seconds or as a ratio International Normalised Ratio or INR.

It is used to diagnose blood disorders which may result in a defect in blood clotting or to monitor medicines that are taken to prevent clotting of blood.

PT/INR evaluates the extrinsic and common pathways of coagulation.

PT is often done along with the activated partial thromboplastin time (aPTT) which measures the intrinsic and common pathway of coagulation. Together PT/INR and aPTT tests are used to assess any defect in the quantity or function of coagulation factors which play an important role in proper clotting of blood.

Difference Between PT & INR

Both PT and INR are actually a single test but expressed in two different ways. They both measure the time taken for blood to clot.

• PT or prothrombin time is a measure of time taken for the blood to clot expressed in seconds.
• The results of the PT test can vary from lab to lab depending on the method employed and the chemicals used.
• To maintain uniformity in test results and to standardize the PT test, INR or international normalized ratio is calculated.
• INR is actually a ratio calculated from PT that adjusts for variations in the PT value so that test results across various labs can be compared.
• An ISI value (International Sensitivity Index) is assigned for all tissue factor that is manufactured. The ISI value 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 the prothrombin time of a normal (control) sample, raised to the power of the ISI value for the analytical system being used.

INR= [PT (patient)/ PT (normal)] ^ISI

Methodology

The test is carried out at 37 °C. It can be performed either manually or on an automated instrument.

• Venous blood is drawn into a test tube which contains liquid sodium citrate ( concentration 3.2%) as an anticoagulant. A capillary or finger stick sample may also be used. If a patient is on warfarin or other anticoagulant therapy, the blood sample should be collected before taking the daily dose.
• After proper mixing, the blood is centrifuged to separate plasma from the blood cells.
• A sample of this plasma is taken in a test tube.
• Next, an excess of calcium(in a phospholipid suspension) is added to the test tube. This reverses the effects of citrate and enables the plasma to clot.
• Finally, thromboplastin or tissue factor ( factor III) is added to the test tube so as to  activate the extrinsic / tissue factor clotting cascade pathway,
• The time the sample takes to clot is measured either manually using a stop-watch or optically using an automated instrument.

Indications of Prothrombin Time Test

• Suspicion of a bleeding or clotting disorder
  • Unexplained or prolonged bleeding
  • Easy bruising
  • Nose bleeds
  • Bleeding gums
  • A clot in veins or legs
• To monitor the effectiveness of a blood-thinning medicine like warfarin
• To diagnose liver disease. Also to assess the severity of the chronic liver disease.
• To assess the ability of the blood to clot. This is done to check if it is safe to do a procedure or surgery that might cause bleeding.

Normal Results

• PT: 11 to 13.5 seconds
• INR: 0.8 to 1.1

For patients on warfarin, the INR is usually kept between 2.0 and 3.0.

Depending on the underlying disease for which warfarin is being taken; the therapeutic range of INR may be adjusted differently.

• If INR is greater than 3.0, it can result in a higher risk for bleeding.
• If INR is lower than 2.0 there is an increased risk for developing a blood clot.

In patients with a greater risk of clotting (eg., those having an artificial heart valve), the therapeutic range may be adjusted between 2.5–3.5.

Indications of Anti-coagulant Therapy

Warfarin or other anticoagulants are given in the following conditions:

• Atrial fibrillation or irregular heartbeat
• The presence of artificial heart valves
• Deep vein thrombosis
• Pulmonary embolism
• Antiphospholipid syndrome
• In myocardial infarction or heart attacks with certain risk factors

Significance of Abnormal Result of Prothrombin Time Test

Increased PT/INR

It means that the blood is clotting more slowly than normal. This could be due to:

• Taking blood-thinning medicines, such as warfarin
• Bleeding disorders: A group of conditions in which there is a defect in the blood clotting mechanism of the body.
• Deficiency of coagulation factors: A high value of PT could indicate a deficiency of coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prower factor).
• Disseminated intravascular coagulation: In this disorder, blood-clots form inside blood vessels which use up the blood’s clotting factors leading to massive bleeding at other body sites.
• Liver disease.
• Low level of vitamin K.

Decreased PT/INR

It means that the blood is clotting too quickly. This could be due to

• Vitamin K containing supplements
• High intake of vitamin K rich foods (liver, broccoli, chickpeas, kale, turnip greens, soybeans, and green tea)
• Estrogen-containing medicines (Oral contraceptive pills and hormone replacement therapy)

If a person is taking warfarin, an abnormally high or low INR may be due to:

• The wrong dose of medicine
• Drinking alcohol
• Certain medicines like vitamins, supplements, antibiotics or medicines for cough and cold. Some antibiotics can increase the PT/ INR value. Barbiturates, oral contraceptive pills and hormone-replacement therapy, and vitamin K supplements can decrease PT /INR.
• Certain foods that interact with warfarin. These include liver, green tea, soybeans, chickpeas, kale, turnip greens spinach, broccoli, cranberries, etc. These foods contain large amounts of vitamin K and can alter the prothrombin time and INR result.

Consult your doctor about what foods should be avoided while taking warfarin.

Also, it is important that the doctor knows about all the medications, health supplements  or foods consumed by the patient so that the results of prothrombin time and INR are interpreted correctly.

Home Testing

Home testing kits for prothrombin time and INR are available for people who need to take blood-thinning medicines for long periods. However, the patient needs to be specially trained for performing this test at home.

References

1. Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier; 2019.
2. Nakano Y, Kondo T, Osanai H, Murase Y, Nakashima Y, Asano H, et al. Clinical usefulness of measuring prothrombin time and soluble fibrin levels in Japanese patients with atrial fibrillation receiving rivaroxaban. J Cardiol. 2014 Sep 2. [Medline].
3. Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007 Jul. 82(7):864-73. [Medline].
4. WHO Expert Committee on Biologic Standardization. 33rd Report. Technical Report Series No 687. Geneva: World Health Organization. 1983.