International Normalized Ratio (INR) Calculator

International Normalized Ratio (INR) Explained

The INR is the preferred parameter in monitoring anticoagulation therapy but is also used to assess the risk of bleeding or coagulation status of patients. Those under therapy with oral anticoagulants are required to monitor INR to adjust the vitamin K antagonists (VKA) doses because these vary between patients.

INR is derived from prothrombin time (PT) which is calculated as a ratio of the patient’s PT to a control PT standardized for the potency of the thromboplastin reagent international sensitivity index (ISI):

INR = (PTpatient / PTnormal)ISI

The variables used can be defined as:

• Prothrombin time (PT) is the actual time in seconds for the anti-coagulated sample of plasma or whole blood to clot after it is added to a thermoplastic reagent.
• The International Normalized Ratio (INR) is the system for reporting the results of blood coagulation tests by standardizing prothrombin time.
• The International Sensitivity Index (ISI) is a value assigned by manufacturers to the batch of tissue factor, indicating how that particular batch of tissue factor compares to an international reference tissue factor. The ISI ranges between 0.94 and 1.4 for more sensitive samples and 2.0 and 3.0 for less sensitive thromboplastins.

The INR helps clinicians evaluate both the extrinsic pathway and the common pathway of coagulation and it is used to measure liverl function, effect of anticoagulants and levels of vitamin K.

The higher the INR, the longer it takes for blood to coagulate (clot). Elevated INR values are indicative of an increased bleeding risk whilst low INR values may suggest risk of thromboembolism complications.

INR interpretation

• INR < 1.1: Healthy range for patients not on anticoagulation medication;
• INR 1.1 - 1.9: Elevated INR level, further investigations required;
• INR 2.0 – 3.0: INR therapeutic level for patients treated with anticoagulation medication;
• INR >3.0: Elevated INR level with increased risk of bleeding.

INR monitoring

Some of the indications for monitoring INR include:

• Baseline sample collection before starting anticoagulation;
• Before elective or non-elective surgery;
• Deficiencies of coagulation factors (fibrinogen and factors II, V, VII or X or combined deficiency);
• Disseminated intravascular coagulation (DIC);
• Monitoring efficiency and safety of warfarin or other anticoagulation therapy (where there is an increased risk of thrombosis);
• As part of liver function tests.

INR monitoring is most commonly required for the patients who are on vitamin K antagonists where the dose is adapted based on INR scores, so that it remains within the therapeutic scores. Subtherapeutic INR may cause thrombosis whilst supratherapeutic INR may cause hermorrhagic complications.

Prolonged INR causes include:

• VKA administration (warfarin inhibits the gamma-carboxylation of the vitamin K-dependent factors, including factors II (prothrombin), VII, IX, and X);
• Heparin administration or direct thrombin inhibitor administration;
• Vitamin K deficiency;
• Disseminated intravascular coagulation (DIC);
• Deficiencies of coagulation factors;
• Antiphospholipid antibodies (lupus anticoagulants).

INR drug interactions and comorbidities

INR values may be prolonged or lowered by interactions with other medication, as summarized in the table below:

Chronic liver disease, acute illnesses such as infections or gastrointestinal illnesses may impact on INR control.

References

Shikdar S, Vashisht R, Bhattacharya PT. International Normalized Ratio (INR) (2020) Treasure Island (FL): StatPearls Publishing.

Schwebach AA, Waybright RA, Johnson TJ. Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Vitamin K Antagonist Reversal: Does One Dose Fit All? Pharmacotherapy. 2019; 39(5):599-608.

Khatib R, Ludwikowska M, Witt DM, Ansell J, Clark NP, Holbrook A, Wiercioch W, Schünemann H, Nieuwlaat R. Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv. 2019 Mar 12;3(5):789-796.