How to decrease International Normalized Ratio (INR) in a patient with cirrhosis using Vitamin K?

From the Guidelines

Vitamin K can be used to decrease INR in cirrhosis patients, with a recommended dose of 1 to 2.5 mg orally for INR values between 4 and 10, as it has been shown to effectively reduce INR within 24 hours without causing resistance to warfarin once it is reinstated 1. The effectiveness of vitamin K in decreasing INR in cirrhosis patients depends on the underlying cause of the coagulopathy. For patients with elevated INR due to vitamin K deficiency, which is common in cirrhosis due to poor nutrition or malabsorption, vitamin K supplementation is recommended.

• The typical regimen is not 10mg subcutaneously or intravenously daily for 3 days, but rather oral administration of 1 to 2.5 mg, which is predictably effective and has the advantages of convenience and safety over parenteral routes.
• Oral vitamin K, 1.0 to 2.5 mg, is sufficient when the INR is between 4 and 10, but larger doses (5 mg) are required when the INR is 10.
• The American Association for the Study of Liver Diseases recommends correction of INR using vitamin K, not fresh frozen plasma (FFP), for procedures with a high risk of bleeding 1.
• Regular monitoring of INR is essential during treatment, as the risk of bleeding increases when the INR exceeds 4, and the risk rises sharply with values above 5 1.
• The mechanism behind vitamin K's action involves its role as a cofactor for the activation of clotting factors II, VII, IX, and X in the liver, which are essential for proper blood coagulation. However, it's also important to consider that vitamin K will only help if the elevated INR is due to vitamin K deficiency and not if it's caused by reduced synthesis of clotting factors from severe liver dysfunction. In cases where vitamin K is ineffective, fresh frozen plasma (FFP) or prothrombin complex concentrate may be necessary, especially before invasive procedures or in active bleeding 1.

From the FDA Drug Label

To correct excessively prolonged prothrombin time caused by oral anticoagulant therapy—2. 5 to 10 mg or up to 25 mg initially is recommended. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition

The recommended initial dose of Vitamin K to decrease International Normalized Ratio (INR) in a patient with cirrhosis is 2.5 to 10 mg or up to 25 mg. The frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition 2.

From the Research

Decreasing International Normalized Ratio (INR) in Patients with Cirrhosis using Vitamin K

• The effectiveness of vitamin K in decreasing INR in patients with cirrhosis is not well established 3, 4, 5, 6, 7
• Studies have shown that the administration of vitamin K may not have a significant impact on INR changes or bleeding events in patients with cirrhosis 3, 4, 5, 6
• A retrospective study found that the use of intravenous vitamin K to correct coagulopathy of cirrhosis may not be beneficial, with only 16.7% of patients achieving a 30% decrease in INR or a reduction in INR to an absolute value of ≤1.5 3
• Another study found that vitamin K administration was not associated with a decrease in INR, and that ICU care, receipt of a blood product, and baseline INR > 1.6 were associated with INR decrease, but not vitamin K administration 4
• A study published in 2023 found that the administration of vitamin K in hospitalized patients with chronic liver disease resulted in minimal INR change, suggesting that this intervention may not have the intended benefit of reducing bleeding risk 5
• A case-control study found that factors associated with response to vitamin K included lower body weight, absence of cirrhosis, and lower bilirubin, and that the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact 6
• An observational study found that the administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events, and that the INR reduction with subsequent doses of vitamin K was not statistically significant 7

Administration of Vitamin K

• The route of vitamin K administration, including oral and intravenous, did not have a significant impact on INR change 5
• The dose of vitamin K, including high-dose intravenous administration, did not have a significant impact on INR change 6
• The frequency of vitamin K administration, including single and multiple doses, did not have a significant impact on INR change 5, 7