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Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

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PT<br />

9236<br />

Prothrombin Time, Plasma<br />

Clinical Information: The prothrombin time (PT) represents the time elapsed between 1) addition of<br />

a standardized mixture of tissue thromboplastin and calcium to citrate anticoagulated plasma and 2)<br />

detection of clot formation, representing fibrin polymerization resulting from the generation of thrombin<br />

which proteolytically transforms fibrinogen to fibrin. Tissue thromboplastin is a mixture of phospholipid<br />

vesicles and tissue factor (TF), a protein cofactor. Tissue thromboplastins have traditionally been prepared<br />

from animal tissue extracts (brain, placenta, lung), however the recent availability of recombinantly<br />

derived human TF combined with purified phospholipid mixtures allows preparation of well-defined<br />

tissue thromboplastin with several potential advantages. Together with phospholipid, TF forms a complex<br />

with coagulation factor VII/VIIa (activated factor VII), providing an enzyme-cofactor complex which, in<br />

the presence of ionic calcium, activates proenzyme coagulation factor X to the enzyme factor Xa. Factor<br />

Xa, in turn, forms a complex with phospholipid, calcium, and activated factor V (Va, a protein cofactor)<br />

to form prothrombinase, which hydrolyzes factor II substrate (prothrombin) to the active coagulant<br />

enzyme thrombin. Thrombin hydrolyzes fibrinogen (factor I) by cleaving specific peptides<br />

(fibrinopeptides A and B), to form fibrin monomer, which assembles into fibrin polymers (a clot). The PT<br />

is not sensitive to deficiencies of coagulation factors VIII, IX, XI, XII ("intrinsic pathway" factors), or<br />

factor XIII, although the TF/VIIa complex can activate factor IX (in addition to factor X). A prolonged PT<br />

indicates deficiency of 1 or more coagulation factors (I, II, V, VII, or X) or the presence of a coagulation<br />

inhibitor. The PT is the most common test used for monitoring oral anticoagulant therapy (warfarin or<br />

Coumadin, and congeners).Oral anticoagulants reduce the activities of the 4 vitamin K-dependent<br />

procoagulant factors (factors II, VII, IX, and X), and the PT is sensitive to 3 of them. The PT requires<br />

standardization because there are numerous thromboplastins and coagulation testing instruments, and they<br />

all vary in their responsiveness to the concentrations or activities of coagulation proteins. The<br />

International Normalized Ratio (INR) is a method of standardizing PT reporting for monitoring the<br />

intensity of oral anticoagulant therapy. The INR is the ratio of the patient's PT to the laboratoryâ€s<br />

mean normal (reference) PT. The International Sensitivity Index (ISI) is an experimentally derived<br />

measurement, usually provided by the thromboplastin manufacturer, reflecting thromboplastin (and PT)<br />

sensitivity to coagulation deficiencies. More sensitive thromboplastins have a low ISI (1.0-1.2), whereas<br />

less sensitive thromboplastins have a higher ISI (eg, 2.0-3.0). Calculation of the INR is as follows: INR =<br />

(Patient's PT/mean PT of reference range)ISI where: INR = International Normalized Ratio ISI =<br />

International Sensitivity Index Recommended INR therapeutic ranges for orally administered drugs are as<br />

follows: Anticoagulation Intensity INR Standard Intensity 2.0-3.0 Higher Intensity 3.0-4.5 The INR is<br />

used only for patients on stable oral anticoagulant therapy. It makes no significant contribution to the<br />

diagnosis or treatment of patients whose PT is prolonged for other reasons. At <strong>Mayo</strong> Clinic and for <strong>Mayo</strong><br />

<strong>Medical</strong> Laboratories' clients, the PT test is performed with a sensitive thromboplastin (ISI 1.0+/- 0.05),<br />

containing phospholipid and recombinantly derived TF.<br />

Useful For: Monitoring intensity of oral anticoagulant therapy when combined with INR reporting<br />

Screening assay to detect deficiencies of 1 or more coagulation factors (factors I, II, V, VII, X) due to:<br />

-Hereditary or acquired deficiency states -Vitamin K deficiency -Liver disease -Specific coagulation<br />

factor inhibitors Screening assay to detect coagulation inhibition ("circulating anticoagulants") associated<br />

with: -Specific coagulation factor inhibitors -Lupus-like anticoagulant inhibitors (antiphospholipid<br />

antibodies) -Nonspecific PT inhibitors (eg, monoclonal immunoglobulins, elevated fibrin degradation<br />

products)<br />

Interpretation: The PT test varies in its sensitivity to the activity of coagulation factors II, V, VII, and<br />

X, and is least sensitive to decreased factor II. According to <strong>Mayo</strong> Clinic Special Coagulation laboratory<br />

validation, using recombinantly derived thromboplastin with ISI close to 1.0, the PT begins to become<br />

prolonged when: Factor II

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