What are the implications of a low International Normalized Ratio (INR)?

From the Guidelines

If you have a low International Normalized Ratio (INR), you should contact your healthcare provider immediately for guidance, as a low INR indicates that blood is clotting more quickly than desired, which is concerning for patients on anticoagulant therapy like warfarin. They may increase your warfarin dosage to achieve the target INR range, typically 2.0-3.0 for most conditions (or 2.5-3.5 for mechanical heart valves) 1. Do not adjust medication on your own. Your provider might recommend more frequent INR monitoring until stable levels are achieved, usually through blood tests every few days initially. Factors that can lower INR include:

• missing warfarin doses
• taking vitamin K supplements
• consuming excessive vitamin K-rich foods (like kale, spinach, or broccoli)
• interactions with certain medications like antibiotics 1. For immediate management, follow your provider's instructions precisely and maintain consistent dietary habits. The INR measures how long it takes your blood to clot compared to a standard, and maintaining the proper range is crucial to prevent dangerous clotting events while avoiding bleeding complications. It is preferable to specify a single INR target for each patient and to recognize that the acceptable range includes 0.5 INR units on each side of this target, as fluctuations in INR are associated with an increased incidence of complications in patients with prosthetic heart valves 1. In patients with current-generation mechanical aortic prosthetic valves and no other thromboembolic risk factors, an INR of 2.5 (range, 2.0–3.0) provides a reasonable balance between the risks of thromboembolism and bleeding 1. However, in patients with an aortic mechanical prosthesis who are at higher risk of thromboembolic complications, the INR should be maintained at 3.0 (range, 2.5–3.5) 1. For patients with a mechanical mitral valve, an INR target of 3.0 (range, 2.5–3.5) provides a reasonable balance between the risks of under- or over-anticoagulation 1. It is essential to note that patient compliance may be challenging with higher INR goals, and regular monitoring is necessary to ensure the INR remains within the target range 1.

From the FDA Drug Label

The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations. Atrial Fibrillation ... the effects of warfarin in reducing thromboembolic events including stroke were similar at either moderately high INR (2.0-4.5) or low INR (1.4-3. 0). For patients with AF and mitral stenosis, anticoagulation with oral warfarin is recommended (7th ACCP) For patients with bioprosthetic valves, warfarin therapy with a target INR of 2.5 (range, 2.0 to 3.0) is recommended for valves in the mitral position and is suggested for valves in the aortic position for the first 3 months after valve insertion.

A low INR is generally considered to be below the target range of 2.0-3.0.

• If the INR is low, the dose of warfarin should be adjusted to maintain a target INR of 2.5.
• The target INR range may vary depending on the specific condition being treated, but in general, an INR below 2.0 is considered low. 2

From the Research

Low INR

• A low INR indicates that the blood is not thin enough, which may not protect against thromboembolic complications 3
• The goal therapeutic INR range for patients treated with warfarin is most commonly 2 to 3 4
• A sub-therapeutic INR may put patients at risk of thromboembolic complications, whereas a supra-therapeutic INR puts patients at risk of bleeding 3
• Careful monitoring of the INR is essential, especially in geriatric or cancer populations who are at an increased risk of major hemorrhage 3
• For patients with stable INRs, frequency of INR testing can be extended from every 4 weeks to up to 12 weeks 4
• Self-testing and self-management can be safe options for patients receiving warfarin who are motivated and show competence 4

Monitoring of Low INR

• Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants 5
• Liquid chromatography-mass spectrometry (LC-MS/MS) is considered the gold standard method for DOAC measurement, but it is time consuming and requires expensive equipment 6
• The general consensus for the assessment of a DOAC is clotting or chromogenic assays using specific standard calibrators and controls 6
• A single test to assay warfarin, dabigatran, rivaroxaban, apixaban, unfractionated heparin, and enoxaparin in plasma can be useful in emergent situations 7

Management of Low INR

• Patients starting anticoagulation therapy should receive education on treatment goals, adverse effects, and monitoring strategy 4
• Physicians deciding whether to prescribe one of the new oral anticoagulants instead of warfarin should assess for possible drug interactions and for renal and hepatic impairment and should consider the financial cost to the patient 4
• No established agents are clinically available to reverse the anticoagulant effect of new oral anticoagulants, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents 5