The prothrombin time (PT, pro time) test is used to evaluate the extrinsic pathway of the coagulation sequence. It represents the time required for a firm fibrin clot to form after tissue thromboplastin (coagulation factor III) and calcium are added to the sample. These added substances directly activate factor X, the key factor in all three coagulation pathways (see Fig. 2-1). Neither platelets nor the factors involved in the intrinsic pathway are necessary for the clot to form.

To give a normal PT result, plasma must have at least 100 mg/dL of fibrinogen (normal: 150 to 400 mg/dL) and adequate levels of factors X, VII, V, and II (prothrombin). Because the test bypasses the clotting factors of the intrinsic pathway, the PT cannot detect the two most common congenital coagulation disorders: (1) deficiency of factor VIII (hemophilia A, or "classic" hemophilia) and (2) deficiency of factor IX (hemophilia B, or Christmas disease). Also, thrombocytopenia does not prolong the PT.

PT measurements are reported as time in seconds or as a percentage of normal activity, or both. Time in seconds indicates the length of time for the blood to clot when chemicals are added in comparison to normal blood with the same chemicals added (control value). A value that is higher than the control sample is considered to be deficient in prothrombin. Some laboratories report the results in percentages that are derived from a plotted graph based on dilutions of the control samples and the time in seconds it takes for the sample to clot; the seconds are then converted to percentages. The time then reflects the percentage of normal clotting time by comparing the client's clotting time to its intersection point with the percentage on the graph. Usually an increase in time for clotting equals a decrease in the percentage of activity, although different laboratories can obtain different results when determining the percentages. This difference is because of the different thromboplastins used as reagents in the testing procedure.

Because the variability in responsiveness to the different thromboplastins has resulted in dosing differences, a thromboplastin has been developed by the first International Reference Preparation. This reagent is used to monitor the therapeutic levels for coagulation during coumarin-type therapy. A standardization of reporting the PT assay test results developed by the World Health Organization has been adopted for this reagent. It is known as the International Normalized Ratio (INR). The INR is calculated with the use of a nomogram developed to demonstrate the relationship between the INR and the prothrombin ratios with the International Sensitivity Index range (values associated with the available thromboplastin reagents from the various companies that develop them). PT evaluation can now be based on the INR and both are reported as PT and its equivalent INR for evaluation and decisions in oral anticoagulation therapy as endorsed by the Committee on Antithrombotic Therapy of the American College of Chest Physicians, the Committee for Thrombosis and Hemostasis, and the International Committee for Standardization in Hematology. The recommended INR therapeutic range for oral anticoagulant therapy is 2.0 to 3.0 in the treatment of venous thrombosis, pulmonary embolism, and the prevention or treatment of systemic embolism. A pro time test system is now available to perform immediate measurement of PT at the bedside using a fresh whole blood sample, reagent cartridges, and a monitor that operates on rechargeable batteries.

Prothrombin is a vitamin K-dependent protein produced by the liver. Thus, any disorder that impairs the liver's ability to use vitamin K or to form proteins (e.g., the various types of cirrhosis) prolongs the PT. Anticoagulants of the coumarin family act by inhibiting hepatic synthesis of the vitamin K-dependent factors II, VII, IX, and X. A natural anticoagulant system dependent on the action of vitamin K on the proteins C and S is different from the activity of this vitamin on coagulation factors II, VII, IX, and X. Protein C acts to neutralize the activity of factors VIIIa and Va, and protein S increases the inactivation of VIIIa and Va by the protein C. Any deficiency of the various factors can alter the balance between the two proteins and result in thrombotic disorders. The tests are performed to determine their functional activity and reveal a tendency toward hypercoagulation and thrombosis or to diagnose a hereditary deficiency.

Because values may vary according to the source of the substances added to the sample and the type of laboratory equipment used, the result is usually evaluated in relation to a control sample obtained from an individual with normal hemostatic function.

Test results are sometimes given as a percentage of normal activity, comparing the client's results against a curve that shows the normal clotting rate of diluted plasma. The normal value in this case is 100 percent; however, the method itself is thought to be inaccurate because dilution affects the clotting process.

Numerous drugs may alter the PT results, including the following:

• Drugs that prolong the PT, such as coumarin derivatives, quinidine, quinine, thyroid hormones, adrenocorticotropic hormone, steroids, alcohol, phenytoin, indomethacin, and salicylates
• Drugs that may shorten the PT, such as barbiturates (especially chloral hydrate), oral contraceptives, and vitamin K³¹
  • Traumatic venipuncture may lead to erroneous results because of activation of the coagulation sequence.
  • Excessive agitation of the sample may erroneously prolong the PT.
  • A fibrinogen level of less than 100 mg/dL (SI units, 1.00 g/L) (normal: 150 to 400 mg/dL [SI units, 1.50-4.00 g/L]) may prolong the PT.

• Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia
• Identification of individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures
• Evaluation of response to anticoagulant therapy with coumarin derivatives and determination of dosage required to achieve therapeutic results
• Differentiation of clotting factor deficiencies of V, VII, and X, which prolong the PT, from congenital coagulation disorders such as hemophilia A (factor VIII) and hemophilia B (factor IX), which do not alter the PT
• Monitoring of effects on hemostasis of conditions such as liver disease, protein deficiency, and fat malabsorption

Nursing Care Before the Procedure

In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I).

• Because many drugs may affect the PT result, all medications taken by the client should be noted.
• If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted.

A venipuncture is performed and the sample collected in a light-blue-topped tube. Traumatic venipunctures and excessive agitation of the sample should be avoided.

Nursing Care After the Procedure

Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample.

• Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn.
• Inspect the site for excessive bruising after the procedure.
  • Bleeding episode: Note and report increase in PT, medications taken that affect the PT and expected test values, symptoms such as bleeding from any area (blood in sputum, feces, urine; bleeding from nose, skin), headache, increased pulse, or pain in the abdomen or back. Report changes related to administration of coumarin-type medication and adjust drug dosage as ordered until desired INR is reached. Protect skin, mucous membranes, and organs from trauma (shaving, brushing teeth, suctioning, intramuscular [IM], subcutaneous [SC], and intravenous [IV] injections, falls, activities that are strenuous, straining). Test for occult blood in body secretions and excretions. Inform client to avoid drugs that potentiate the effect of coumarin-type drugs. Instruct client in importance and frequency of PT laboratory testing.
  • Venous thrombosis: Note and report decreases in PT or other factors predisposing to formation of venous thrombi. Provide leg exercises and adequate fluid intake. Advise client to avoid crossing legs, wearing constrictive clothing, or participating in other activities that impair circulation. Inform client of importance and frequency of PT testing.
  • Critical values: Notify the physician immediately of an increase of greater than 40 seconds or 15 seconds above the control time. Prepare the client for administration of IM vitamin K or IV frozen plasma. Notify the physician immediately of an increase of greater than 24 seconds in individuals with a liver disease if they are experiencing hypoprothrombinemia from vitamin K deficiency. Notify the physician immediately if there is a decrease of less than 8 to 9 seconds or 11 to 12 seconds below the control time. Prepare the client for possible SC administrations of heparin.