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The test measures how long it takes for your blood to begin to form clots. Prothrombin is a plasma protein produced by the liver. Clotting is caused by a series of clotting factors which activate each other, including the conversion of prothrombin to thrombin. The test used to measure the activity of this clotting factor is called the prothrombin time or PT. A tightly controlled version of the PT called the International Normalised Ratio (INR) is used to measure the effect of anticoagulant drugs such as warfarin.

About

Prothrombin is a plasma protein with a molecular weight of 68,700. It is an unstable protein that can split easily into smaller compounds, one of which is thrombin. Prothrombin is formed continually by the liver, and it is continually being used throughout the body for blood clotting. If the liver fails to produce prothrombin, in a day or so prothrombin concentration in the plasma falls too low to provide normal blood coagulation. Vitamin K is required by the liver for normal activation of prothrombin, as well as other clotting factors. Therefore, either lack of vitamin K or the presence of liver disease that prevents normal prothrombin formation can decrease the prothrombin concentration so low that a bleeding tendency results.


The prothrombin time (PT) is used as a screening test to detect a deficiency of one or more of the clotting factors of the extrinsic coagulation system (I, II, V, VII, or X) due to a hereditary or acquired deficiency, liver disease, vitamin K deficiency, or presence of inhibitors. Inhibitors include specific coagulation factor inhibitors, Lupus-like anticoagulant inhibitors (eg, antiphospholipid antibodies), and nonspecific prothrombin time inhibitors (eg, monoclonal immunoglobulins, elevated fibrin degradation products).


The PT results produced by different assays may vary significantly as there are differences in the activity of the tissue factor and the instrument used to perform the test. Tissue factor is isolated from a variety of sources by assay manufacturers, and different batches may have different activity. Calculation of the international normalized ratio (INR) addresses this problem by normalizing the PT result. For this reason, INR is used to monitor oral anticoagulant therapy (warfarin or Coumadin).


Warfarin inhibits the enzyme, vitamin K epoxide reductase complex 1 (VKOR c1), responsible for converting vitamin K to its active, reduced form. By inhibiting VKOR c1, warfarin decreases the available active form of vitamin K in the tissues. Thus, when warfarin is given to a patient, the amounts of active prothrombin and factors VII, IX, and X, all formed by the liver degrade and are replaced by inactive factors. Although the coagulation factors continue to be produced, they have greatly decreased coagulant activity.


Bleeding is the primary adverse reaction associated with warfarin use and is among the top 10 drugs with the largest number of serious adverse events. For these reasons, monitoring therapy closely and adjusting dose accordingly is critical.

Preparation

No test preparation is needed. If the patient is receiving anticoagulant therapy, the specimen should be collected before the daily dose is taken. It is essential the blood is taken quickly and smoothly and that the anticoagulant bottle is filled exactly to the designated mark or the result may be inaccurate.

Methodology

We use Roche CoaguChek Pro II system with an electrochemical determination of the PT and aPTT time after activation of coagulation cascade.

Indications

If you are taking an anticoagulant drug, your doctor will check your INR regularly to make sure that your prescription is working properly and that the INR is appropriately increased. There is no set frequency for doing the test. Your doctor will request it often enough to make sure that the drug dose is correct. Occasionally the PT or INR may be used on a patient who is not taking anticoagulant drugs—to check for a bleeding disorder, liver disease or vitamin K deficiency, or to ensure clotting ability before surgery.

Interpretation

Reference ranges: Prothrombin Time (PT): 11-13.5 seconds; International Normalised Ratio (INR) 0.8-1.1 We report PT results that have been adjusted to the International Normalised Ratio (INR). Patients on anticoagulant drugs usually have a target INR of 2.0 to 3.0 (i.e. a prothrombin time 2 to 3 times as long as in a normal patient, using standardised conditions). For some patients who have a high risk of clot formation, the INR needs to be higher: about 3.0 to 4.0. Your doctor will use the INR to adjust your drug to get the PT into the range that is right for you. Increased prothrombin time or INR means that your blood is taking longer to form a clot. If you are not taking anticoagulant drugs and your PT is prolonged, additional testing may be necessary to determine the cause.

Interpretation of PT and aPTT in Patients with a Bleeding or Clotting Syndrome

The PT is often performed along with another clotting test called the aPTT (or sometimes the PTT or KCCT). Comparison of the two results can give your doctor information as to the cause of a bleeding problem.
PT result aPTT result Possible conditions present
Prolonged Normal Liver disease, decreased vitamin K, decreased or defective factor VII
Normal Prolonged Decreased or defective factor VIII, IX, XI or XII, von Willebrand disease, or lupus anticoagulant present
Prolonged Prolonged Decreased or defective factor I, II, V or X, liver disease, disseminated intravascular coagulation (DIC)
Normal Normal Decreased platelet function, thrombocytopenia, factor XIII deficiency, mild deficiencies in other factors, a mild form of von Willebrand’s disease, weak collagen

Disclaimer

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario. Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

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