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Prothrombin Time (PT) and the International Normalized Ratio (INR)


Definition


  • The PT assesses the coagulation activity of the extrinsic and common coagulation pathways.
  • Tissue thromboplastin (tissue factor) is used as a potent activator of the coagulation system in the presence of added calcium. Currently, recombinant tissue factor is used in most commercial reagents. The potency of tissue factor explains the shortness of clotting (in seconds) in the assay.
  • Normal ranges:
    • PT: 9.6 " “12.4 seconds (may vary slightly from laboratory to laboratory)
    • INR: 1.0 ratio (remains constant independent of equipment or reagent used)

Use


  • Evaluation of clotting disorders that may involve the extrinsic coagulation mechanism (factor VII) and the common pathway (factors II, V, X and fibrinogen). In these situations, the PTT should be ordered in parallel with the PT. PT is not sensitive to clotting factors if they are modestly decreased (>30%). In addition, it is not sensitive to abnormalities in factors involved in the intrinsic coagulation pathway (factors XII, XI, IX, and VIII) or in protein C or S deficiencies.
  • Evaluation of liver function reflecting abnormalities in factors VII, II, X, IX and V (but not VIII).
  • To monitor long-term oral anticoagulant therapy with coumarin and indanedione derivatives. PT is prolonged >PTT, and more consistently so. Factor V is not affected by oral anticoagulants, whereas it may be decreased in liver disease.
    • INR is the preferred reporting to monitor patients on vitamin K antagonist therapy. In all other circumstances, the use of PT is encouraged rather than INR. The recommended range for INR during most indications for oral anticoagulants is 2 " “3, or 2.5 " “3.5 for patients with mechanical heart valves.

Interpretation


  • Marked prolongation of the PT in liver disease indicates advanced disease.
  • Marked elevation of INR in patients receiving vitamin K antagonists is a marker of excessive anticoagulation and requires prompt action contrariwise, an INR below 2.0 reflects insufficient anticoagulation.
  • Combined abnormal PT and PTT is found under two circumstances:
    • Medical: administration of oral anticoagulants, DIC, liver disease, vitamin K deficiency, massive transfusions
    • Coagulation factor abnormalities: dysfibrinogenemias; factors V, X, and II defects

Limitations


  • Preanalytic errors:
    • Partially clotted specimens due to poor mixture with the anticoagulant (3.2 sodium citrate, as offered by manufacturers blue top vacuum tubes)
    • Over- or underfilled test tubes, altering the ratio of blood (9 parts) to anticoagulant (1 part)
  • Analytic errors: Hemolyzed, lipemic, or icteric plasma may interfere with photoelectric measuring instruments (assay may have to be repeated on a mechanical clot measuring instrument)
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