What is the significance of a Prothrombin Time (PT) of 3.18 and International Normalized Ratio (INR) of 34 in a patient on 2mg of Coumadin (Warfarin), with a previous PT of 3.4 and INR of 36?

From the Guidelines

I recommend holding the Coumadin (warfarin) dose today and rechecking the INR tomorrow. The current INR of 3.18 and PT of 34 seconds indicate that the patient is above the typical therapeutic range (INR 2.0-3.0 for most indications), though not dangerously so, as suggested by the guidelines for management of VTE from the NCCN 1. Since the previous values were similar (PT 3.4, INR 36), this suggests a stable but supratherapeutic anticoagulation status. Holding a dose of warfarin will allow the INR to decrease slightly, as warfarin has a slow onset and clearance from the body, with its anticoagulant effect reaching its peak after 72–96 h and a duration of action of 2–5 days 1.

After rechecking tomorrow, if the INR is trending down toward the therapeutic range, resume the warfarin at a reduced dose of 1.5mg daily instead of 2mg. This small dose reduction is appropriate since the INR elevation is modest. Monitor the INR again in 3-5 days to ensure it's moving into the target range. Key considerations in managing warfarin therapy include:

• Frequent blood sampling to maintain adequate, but not excessive, dosing 1
• Potential interactions between chemotherapeutic agents and warfarin, which can affect INR levels 1
• Increased risk of bleeding, particularly in patients with cancer, which may not be related to INR levels 1 If the patient shows any signs of bleeding (bruising, blood in urine/stool, nosebleeds), they should seek immediate medical attention. The elevated INR indicates excessive inhibition of vitamin K-dependent clotting factors (II, VII, IX, X), which increases bleeding risk.

From the FDA Drug Label

24The PT should be determined daily after the administration of the initial dose until PT/INR results stabilize in the therapeutic range. Intervals between subsequent PT/INR determinations should be based upon the physician’s judgment of the patient’s reliability and response to warfarin sodium tablets in order to maintain the individual within the therapeutic range Acceptable intervals for PT/INR determinations are normally within the range of one to four weeks after a stable dosage has been determined

• The current INR is 34, and the previous INR was 36, both of which are above the therapeutic range.
• The patient is taking 2mg of Coumadin.
• According to the drug label, PT/INR determinations should be based on the physician's judgment to maintain the patient within the therapeutic range.
• The label does not provide specific guidance on dosage adjustments for INR values above the therapeutic range.
• Therefore, the decision on how to adjust the Coumadin dosage should be made based on the physician's clinical judgment, taking into account the patient's individual response to the medication and other relevant factors 2.

From the Research

Patient Information

• PT: 3.18
• INR: 34
• Coumadin dose: 2mg
• Previous PT: 3.4
• Previous INR: 36

Relevant Studies

• A study published in the American journal of clinical pathology in 2012 3 found that an INR higher than 9 is associated with a high risk of bleeding, and that withholding warfarin or giving vitamin K treatment may not be effective in reducing the INR within 24 hours.
• A prospective cohort study published in Thrombosis and haemostasis in 2010 4 found that a single 2.5 mg dose of oral vitamin K can effectively treat INR values in excess of 10, with a low rate of major bleeding.
• A study published in Nutrition reviews in 2005 5 found that high vitamin K intake can decrease the therapeutic effectiveness of warfarin, while poor vitamin K status can increase the sensitivity to small changes in vitamin K intake.
• A UK study published in Thrombosis research in 2021 6 found that correction of INR in major bleeding related to vitamin K antagonists is associated with better survival, and that higher doses of vitamin K (10 mg) are more likely to correct INR than lower doses (5 mg).
• A retrospective cohort study published in Journal of thrombosis and haemostasis in 2020 7 found that vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10.

Possible Treatment Options

• Withholding warfarin or giving vitamin K treatment may not be effective in reducing the INR within 24 hours 3.
• A single 2.5 mg dose of oral vitamin K may be effective in treating INR values in excess of 10 4.
• Higher doses of vitamin K (10 mg) may be more likely to correct INR than lower doses (5 mg) 6.
• Vitamin K administration may not be associated with improved clinical outcomes in asymptomatic patients with an INR > 10 7.