What product to administer when International Normalized Ratio (INR) is subtherapeutic?

From the Guidelines

When the INR is low, bridging anticoagulation with either intravenous UFH or subcutaneous LMWH is recommended. This approach is based on the 2014 AHA/ACC guideline for the management of patients with valvular heart disease 1. The guideline suggests that bridging anticoagulation can minimize the risk of adverse events in patients who are undergoing invasive or surgical procedures with a mechanical heart valve and any thromboembolic risk factor.

Key Considerations

• The risk of thromboembolism can be minimized by anticoagulation with alternative agents that can be stopped right before and restarted right after the surgical procedure, such as "bridging therapy" 1.
• Patients at high risk of thrombosis include all patients with mechanical MVR or tricuspid valve replacements and patients with an AVR and any risk factors for thromboembolism, such as AF, previous thromboembolism, or hypercoagulable condition 1.
• When interruption of VKA therapy is needed, VKA is stopped 2 to 4 days before the procedure and restarted as soon as bleeding risk allows, typically 12 to 24 hours after surgery 1.

Management of Low INR

• In patients with an INR of 5 to 10, excessive anticoagulation can be managed by withholding VKA and monitoring the level of anticoagulation with serial INR determinations 1.
• In patients with an INR >10 who are not bleeding, it is prudent to administer 1 mg to 2.5 mg of oral vitamin K1 (phytonadione) in addition to holding VKA therapy 1.
• Bridging anticoagulation with UFH or LMWH is the preferred approach when the INR is low, as it can reduce the risk of thromboembolism and minimize the risk of adverse events 1.

From the FDA Drug Label

The dosing of warfarin sodium tablets must be individualized according to patient’s sensitivity to the drug as indicated by the PT/INR It is recommended that warfarin sodium tablets therapy be initiated with a dose of 2 to 5 mg per day with dosage adjustments based on the results of PT/INR determinations. Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily.

When the INR is low, the patient should take the prescribed dose of warfarin as soon as possible on the same day if a dose is missed. The dose should not be doubled to make up for missed doses.

• The patient's PT/INR should be monitored regularly to adjust the warfarin dose.
• The warfarin dose may need to be increased to achieve a therapeutic INR range.
• The patient should consult their physician for guidance on adjusting the warfarin dose when the INR is low 2.

From the Research

Product to Give When INR is Low

When the International Normalized Ratio (INR) is low, it indicates that the blood is not thin enough, and the patient may be at risk for thrombosis. The following products can be considered:

• Warfarin: The dose of warfarin may need to be adjusted to achieve a therapeutic INR range 3
• Low-molecular-weight heparin (LMWH): LMWH can be used as a bridging anticoagulant during interruption of warfarin therapy, but it may alter the point-of-care assay for INR 4, 5
• Vitamin K1: Not typically used to increase INR, but rather to decrease INR in cases of elevated INR 3

Considerations for Product Selection

When selecting a product to give when INR is low, the following considerations should be taken into account:

• The patient's underlying medical condition and risk for thrombosis
• The patient's current anticoagulation regimen and any potential interactions with other medications
• The need for frequent INR monitoring to adjust the dose of warfarin or other anticoagulants
• The potential for LMWH to alter the point-of-care assay for INR, and the need for laboratory measurement of INR in patients receiving LMWH 5

Dosing and Administration

The dosing and administration of warfarin and LMWH should be guided by the patient's INR results and clinical factors, such as:

• Initial dose of warfarin: 5 mg (or 2-4 mg in the very elderly) 3
• Adjusting the dose of warfarin: based on INR results, with most changes altering the total weekly dose by 5-20% 3
• LMWH dosing: fixed-dose subcutaneous LMWH once daily, with the dose depending on the patient's renal function and body weight 6