Clinical and Interpretive

The prothrombin time (PT) represents the time elapsed between 1) addition of a standardized mixture of tissue thromboplastin and calcium to citrate anticoagulated plasma and 2) detection of clot formation, representing fibrin polymerization resulting from the generation of thrombin, which proteolytically transforms fibrinogen to fibrin. A prolonged PT indicates deficiency of 1 or more coagulation factors (I, II, V, VII, or X) or the presence of a coagulation inhibitor. The PT is the most common test used for monitoring oral anticoagulant therapy (warfarin or Coumadin, and congeners). Oral anticoagulants reduce the activities of the 4 vitamin K-dependent procoagulant factors (factors II, VII, IX, and X), and the PT is sensitive to 3 of them. The PT requires standardization because there are numerous thromboplastins and coagulation testing instruments, and they all vary in their responsiveness to the concentrations or activities of coagulation proteins. The international normalized ratio (INR) is a method of standardizing PT reporting for monitoring the intensity of oral anticoagulant therapy. The INR is the ratio of the patient’s PT to the laboratory’s mean normal (reference) PT. The international sensitivity index (ISI) is an experimentally derived measurement, usually provided by the thromboplastin manufacturer, reflecting thromboplastin (and PT) sensitivity to coagulation deficiencies. More sensitive thromboplastins have a low ISI (1.0-1.2), whereas less sensitive thromboplastins have a higher ISI (eg, 2.0-3.0).

Calculation of the INR is as follows:
INR = (Patient’s PT/mean PT of reference range) ISI where:
-INR=international normalized ratio
-ISI=international sensitivity index

The INR is used only for patients on stable oral anticoagulant therapy. It makes no significant contribution to the diagnosis or treatment of patients whose PT is prolonged for other reasons.

Recommended INR therapeutic ranges for orally administered drugs are as follows:
-Anticoagulation intensity: INR
-Standard intensity: 2.0 to 3.0
-Higher intensity: 3.0 to 4.5