What is PT/INR (Prothrombin Time International Normalized Ratio)?
PT/INR is a standardized laboratory test that measures how long it takes blood to clot, specifically designed and validated exclusively for monitoring patients on vitamin K antagonist (warfarin) therapy—not as a general predictor of bleeding risk. 1, 2, 3
Definition and Calculation
Prothrombin Time (PT) measures the time (in seconds) it takes for blood plasma to clot after adding tissue factor (thromboplastin) reagent, reflecting the activity of vitamin K-dependent coagulation factors VII, X, II, and fibrinogen 1, 3
International Normalized Ratio (INR) is calculated using the formula: INR = (Patient PT / Mean Normal PT)^ISI, where ISI is the International Sensitivity Index of the thromboplastin reagent used 1, 3
The INR system was introduced by the World Health Organization in 1983 to standardize PT results across different laboratories, reagents, and instruments, providing a common basis for communicating results and interpreting therapeutic ranges 1, 3
Primary Clinical Purpose
The INR was specifically designed and validated ONLY for monitoring vitamin K antagonist (warfarin) therapy—it should not be used as a universal predictor of bleeding risk in patients not taking warfarin 2, 4
The American College of Cardiology and American Heart Association emphasize that using INR to predict bleeding in non-warfarin patients lacks validation and biological plausibility 2, 4
A systematic review found weak or no association between pre-procedural INR and bleeding in 78 out of 79 studies assessed, with sensitivity under 50% for bleeding prediction 2
Therapeutic Monitoring
For warfarin therapy, most patients require a therapeutic INR range of 2.0 to 3.0 for conditions including venous thromboembolism, atrial fibrillation, and mechanical heart valves 1, 3
An INR greater than 4.0 provides no additional therapeutic benefit and significantly increases bleeding risk 3
PT/INR should be determined daily after initiating warfarin until results stabilize in the therapeutic range, then monitored at intervals of one to four weeks once stable dosing is achieved 3
Technical Considerations and Limitations
PT is measured in seconds and depends heavily on the specific thromboplastin reagent and measurement technique used, which is why conversion to INR using the ISI is essential 1, 5
Different thromboplastin types exist (human, rabbit, bovine brain tissue), and reagents can be "plain" (Quick method) or "combined" with depleted plasma (Owren method) 1
Even when laboratories use identical thromboplastin reagents and coagulometers, reported INR values can still differ due to variations in ISI values and technical factors 5
The scientific name for PT is "tissue factor-induced coagulation time," though PT remains the term used in clinical practice 1
Critical Clinical Pitfalls to Avoid
Never use INR to assess bleeding risk in patients NOT on warfarin—this includes patients with liver disease, coagulopathy, or elevated INR from other causes 2, 4
The American Society of Hematology states that plasma transfusion to correct mildly elevated INR values (such as INR 1.4) in non-warfarin patients lacks biological plausibility and exposes patients to unnecessary risk without evidence of benefit 2, 4
In liver disease patients, INR is a poor predictor of bleeding risk despite its use in MELD scoring—consider viscoelastic testing (TEG/ROTEM) instead for coagulation assessment 2, 4
Heparin can interfere with PT/INR measurements; blood should be drawn at least 5 hours after IV heparin bolus, 4 hours after stopping continuous infusion, or 24 hours after subcutaneous injection 3
Historical Context
The first proposed therapeutic PT range was published in 1942, targeting a PT ratio of 1.5 to 2.7 based on clinical experience with dicoumarol 1
The 1986 American College of Chest Physicians guidelines established that INRs above 2.0 represent the threshold for increased hemorrhagic complications 1
Multiple international reference preparations have been established since 1976, with the first human combined thromboplastin (coded 67/40) assigned an ISI value of 1.0 by definition 1