What are the causes of an elevated International Normalized Ratio (INR)?

From the Guidelines

Elevated International Normalized Ratio (INR) is primarily caused by warfarin therapy, vitamin K deficiency, or liver disease.

Causes of Elevated INR

• Warfarin therapy: The most common cause of an elevated INR is warfarin therapy, which works by inhibiting the production of vitamin K-dependent clotting factors in the liver 1.
• Vitamin K deficiency: A deficiency in vitamin K can also lead to an elevated INR, as vitamin K is necessary for the production of clotting factors in the liver.
• Liver disease: Liver disease, such as cirrhosis, can also cause an elevated INR, as the liver is responsible for producing clotting factors.

Management of Elevated INR

• Stopping warfarin: The first step in managing an elevated INR is to stop warfarin therapy, which can help to lower the INR over several days 1.
• Administering vitamin K: Administering vitamin K1 can help to quickly lower the INR, with oral administration being the preferred route due to its convenience and safety 1.
• Infusing fresh plasma or prothrombin concentrate: In cases where rapid reversal of anticoagulation is required, infusing fresh plasma or prothrombin concentrate can help to quickly lower the INR 1.

Risk of Bleeding

• The risk of bleeding increases with INR values above 4, and the risk rises sharply with values above 5 1.
• Patients with INR values above 9 are at a higher risk of bleeding, and vitamin K1 should be administered in a dose of 3 to 5 mg orally to help lower the INR 1.

From the Research

Causes of Elevated International Normalized Ratio (INR)

The causes of an elevated International Normalized Ratio (INR) can be varied and multifaceted. Some of the key factors that contribute to an elevated INR include:

• Warfarin usage: Studies have shown that warfarin can increase the risk of elevated INR, particularly in patients who are taking multiple medications or have underlying health conditions 2.
• Diarrhea: Diarrhea can lead to malabsorption of vitamin K, which can predispose patients taking warfarin to INR elevations 3.
• Stress: Stressful events, physical or psychological, can elevate the INR, although the mechanism for this occurrence is unknown 4.
• Hemodialysis: Patients undergoing hemodialysis are at a higher risk of falsely elevated INRs 5.
• Age and comorbidities: Older age, renal failure, and alcohol use are associated with a higher risk of bleeding in patients with elevated INR 6.
• Drug interactions: Certain medications, such as acetaminophen, ramipril, and furosemide, can interact with warfarin and increase the risk of elevated INR 2.
• Decreased vitamin K intake: Decreased dietary intake of vitamin K can contribute to elevated INR, particularly in patients taking warfarin 3.

Patient-Specific Factors

Patient-specific factors can also play a role in elevated INR, including:

• Sex: Males are 9% more likely to report increased INR as an adverse event compared to females 2.
• Age: The risk of elevated INR increases with age, particularly in individuals older than 80 2.
• Comorbidities: Underlying health conditions, such as liver disease or malabsorption, can increase the risk of elevated INR.