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

From the Guidelines

To decrease INR in a cirrhosis patient, correction of a prolonged INR with FFP is not recommended due to the lack of evidence supporting its efficacy and the potential risks associated with FFP transfusion, as stated in the EASL clinical practice guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis 1.

Rationale

The use of FFP to correct a prolonged INR in patients with cirrhosis is a common practice, but its effectiveness is not supported by strong evidence. In fact, studies have shown that FFP transfusion does not significantly improve thrombin generation in patients with cirrhosis, and its use is associated with potential risks such as transfusion-related acute lung injury, transfusion-associated circulatory overload, and allergic reactions 1.

Alternative Approaches

Instead of using FFP, other approaches can be considered to manage bleeding risk in patients with cirrhosis. These include:

• Using viscoelastic tests, such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM), to guide blood product transfusion 1
• Administering prothrombin complex concentrate (PCC) to correct coagulopathy, although its use is still controversial and requires further study 1
• Addressing underlying liver dysfunction and optimizing nutritional support to improve coagulation 1

Key Considerations

When managing bleeding risk in patients with cirrhosis, it is essential to consider the following:

• The lack of evidence supporting the use of FFP to correct a prolonged INR
• The potential risks associated with FFP transfusion
• The importance of addressing underlying liver dysfunction and optimizing nutritional support
• The need for further study on the use of alternative approaches, such as PCC and viscoelastic tests, to guide blood product transfusion.

From the FDA Drug Label

1. 2 Warfarin Changes in INR have been reported postmarketing in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range.

The FDA drug label does not provide information on how to decrease International Normalized Ratio (INR) in a patient with cirrhosis, but it does mention that changes in INR have been reported in patients receiving rifaximin and warfarin concomitantly, and that dose adjustment of warfarin may be needed to maintain target INR range 2.

From the Research

Decreasing International Normalized Ratio (INR) in Patients with Cirrhosis

To decrease INR in patients with cirrhosis, several studies have investigated the effectiveness of vitamin K administration. The findings of these studies are summarized below:

• Vitamin K Administration:
  • A study published in 2023 3 found that high-dose intravenous vitamin K administration resulted in a decrease in INR from 1.89 to 1.40 over 3 days in responders, primarily patients with cirrhosis.
  • However, another study from 2016 4 found that vitamin K administration did not affect INR changes or bleeding events in hospitalized patients with cirrhosis.
  • A 2017 study 5 also found that intravenous vitamin K was not effective in correcting cirrhosis-associated coagulopathy, with only 16.7% of patients achieving a 30% decrease in INR or a reduction in INR to ≤1.5.
• Route and Dose of Vitamin K Administration:
  • A 2023 study 6 found no difference in absolute INR change between single versus multiple dose administration or between oral and intravenous administration of vitamin K.
• Effectiveness of Vitamin K Supplementation:
  • A literature review from 2008 7 suggested that vitamin K supplementation may decrease variability of INRs in patients with a history of unstable INRs, although the success varies among patients.
  • However, the same review noted that another prospective study found no difference in the time in the therapeutic range in patients randomized to vitamin K compared with placebo.
• Clinical Implications:
  • The studies suggest that vitamin K administration may not have a significant impact on decreasing INR in patients with cirrhosis, and its use may not be beneficial in this population 4, 5, 6.
  • Further studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K 3 and to clarify the true effects of vitamin K supplementation 7.