Why is the International Normalized Ratio (INR) worsening despite being on Coumadin (warfarin)?

From the Guidelines

If your INR is worsening despite being on Coumadin (warfarin), the most effective approach to manage this is to stop warfarin and administer oral vitamin K1, 1 to 2.5 mg, which can rapidly lower the INR to a safe range within 24 hours 1.

Causes of Worsening INR

Several factors may be contributing to the worsening INR, including:

• Medication interactions
• Dietary changes, such as increased consumption of vitamin K-rich foods
• Illness or infection
• Missed doses of warfarin
• Inconsistent vitamin K intake

Management of Elevated INR

According to the American College of Chest Physicians, the following approaches can be taken to lower an elevated INR:

• Stop warfarin and administer oral vitamin K1, 1 to 2.5 mg, which can lower the INR to a safe range within 24 hours 1
• Infuse fresh plasma or prothrombin concentrate for more rapid reversal
• Reduce or omit the next dose of warfarin and resume at a lower dose when the INR approaches the desired range

Key Considerations

• Regular monitoring of INR is crucial to maintain therapeutic anticoagulation
• Consistent vitamin K intake from foods like leafy greens can help stabilize warfarin efficacy
• Avoid activities with bleeding risk and watch for unusual bruising or bleeding
• Do not take any new medications, including over-the-counter products or supplements, without consulting your healthcare provider
• Warfarin dose adjustments may be necessary, typically ranging from 2-10mg daily, based on your target INR (usually 2-3 for most conditions) 1

From the FDA Drug Label

Numerous factors, alone or in combination, including changes in diet, medications, botanicals and genetic variations in the CYP2C9 and VKORC1 enzymes may influence the response of the patient to warfarin The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: ENDOGENOUS FACTORS: blood dyscrasias — diarrhea hyperthyroidism see CONTRAINDICATIONS elevated temperature poor nutritional state cancer hepatic disorders steatorrhea collagen vascular disease infectious hepatitis vitamin K deficiency congestive heart failure jaundice EXOGENOUS FACTORS: Potential drug interactions with warfarin sodium tablets are listed below by drug class and by specific drugs.

The International Normalized Ratio (INR) may be worsening despite being on Coumadin (warfarin) due to various factors, including:

• Changes in diet: alterations in vitamin K intake
• Medications: interactions with other drugs that affect warfarin metabolism or enhance its anticoagulant effect
• Botanicals: interactions with herbal supplements
• Genetic variations: polymorphisms in the CYP2C9 and VKORC1 enzymes that affect warfarin metabolism
• Endogenous factors: underlying medical conditions such as liver disease, cancer, or hyperthyroidism
• Exogenous factors: other medications or substances that interact with warfarin 2

From the Research

Possible Reasons for Worsening INR

• The International Normalized Ratio (INR) may be worsening despite being on Coumadin (warfarin) due to various factors, including inter-individual differences and environmental factors that affect warfarin's mode of action 3.
• A supra-therapeutic INR puts patients at risk of bleeding, whereas a sub-therapeutic INR may not protect against thromboembolic complications, highlighting the importance of maintaining the INR within the therapeutic range 3.
• Research suggests a lack of anticoagulation control during warfarin therapy in different settings, emphasizing the need for careful monitoring of the INR, especially in high-risk populations such as the geriatric or cancer populations 3.

Factors Influencing INR Normalization

• The rate of INR normalization after excessive anticoagulation is influenced by factors such as the steady-state warfarin dose, advanced age, and extreme elevation in INR 4.
• Decompensated congestive heart failure and active cancer are also significant risk factors for prolonged delay in return of the INR to within the therapeutic range 4.
• The use of oral vitamin K has been shown to effectively reduce the INR value in patients with asymptomatic excessive prolongation of their INR results, with 1 mg of oral vitamin K reliably reducing the INR to the therapeutic range within 24 hours 5.

Management of Elevated INR

• For patients with INR values in excess of 10, a single 2.5 mg dose of oral vitamin K has been shown to be a reasonable treatment, with a low rate of observed major bleeding 6.
• The reliability of INR results ≥4.5 has been assessed, with good correlation between point-of-care and laboratory INR methods, suggesting that laboratory INRs may not be necessary for clinical management of patients with INRs >4.5 7.