Warfarin : INR not not in the therapeutic range triage

The management of patients with an International Normalized Ratio (INR) that falls outside the therapeutic range is a critical aspect of anticoagulation therapy, particularly for those on warfarin. The INR is a standardized measure used to assess the coagulation status of patients, and maintaining it within the therapeutic range is essential to minimize the risks of thromboembolic events and bleeding complications. When a patient's INR is found to be outside this range, it is imperative to conduct a thorough assessment to identify potential causes and implement appropriate management strategies.

First and foremost, adherence to warfarin therapy must be evaluated. Non-adherence can lead to significant fluctuations in INR levels, resulting in either sub-therapeutic or supra-therapeutic values (Türen & Turen, 2022). Factors contributing to non-adherence may include missed doses or accidental overdosing, which can be exacerbated by a lack of understanding of the medication's importance and its interactions with food and other substances (Türen & Turen, 2022). Additionally, the use of other medications, including over-the-counter products, vitamins, and herbal remedies, can significantly impact INR levels. For instance, certain herbal supplements may potentiate the effects of warfarin, while others may reduce its efficacy (Kılıç, 2017).

Furthermore, lifestyle factors such as alcohol consumption and dietary habits must be assessed. Alcohol can potentiate warfarin's effects, leading to increased INR levels, while dietary changes, particularly in the intake of vitamin K-rich foods like green leafy vegetables, can counteract warfarin's anticoagulant effects (Sekaggya et al., 2016). Acute illnesses, weight changes, and smoking cessation also play crucial roles in INR variability; for example, acute illnesses can increase warfarin sensitivity, while weight gain may necessitate dosage adjustments due to altered drug metabolism (Ham et al., 2013).

1. Adherence to Warfarin Treatment

Have you missed any doses of warfarin recently?

Yes No

Have you taken any extra doses by mistake?

Yes No

2. Medication Use

Have you started any new medications, including over-the-counter products, vitamins, or herbal remedies?

Yes No

Have you stopped taking any regular medications?

Yes No

3. Alcohol and Substance Use

Has there been any change in your alcohol consumption?

Yes No

Have you used any recreational drugs recently?

Yes No

Alcohol

Acute alcohol intake (e.g., binge drinking) can inhibit warfarin metabolism, leading to a higher INR and increased bleeding risk.
Chronic heavy use can induce liver enzymes, which may lower warfarin levels and decrease INR over time, but it also damages the liver’s ability to produce clotting factors.
Unpredictable drinking patterns make warfarin control more difficult.
It's important to note that the American Heart Association recommends avoiding alcohol or consuming it in moderation while on warfarin therapy

Over-the-counter (OTC) medications

NSAIDs (e.g., ibuprofen) and aspirin increase bleeding risk by inhibiting platelet function (even if they do not always raise INR itself).
Acetaminophen (paracetamol) in high doses or with prolonged use can potentiate warfarin, raising INR.
Certain cold and flu remedies may contain multiple ingredients (like decongestants, antihistamines, or acetaminophen), so cumulative effects on warfarin and INR should be considered.
Herbal supplements (e.g., St. John’s Wort, cranberry, ginger, turmeric) can also raise or lower INR by affecting metabolism, clotting factors, or platelet function.

4. Diet and Nutrition

Have you made any significant changes to your diet?

Yes No

Have you consumed foods high in vitamin K (e.g., green leafy vegetables) more or less than usual?

More Less No Change

Have you been drinking cranberry juice?

Yes No

5. General Health

Have you experienced any recent weight loss or gain?

Yes No

Have you been ill recently, particularly with any gastrointestinal symptoms like diarrhea or vomiting?

Yes No

Have you recently quit smoking?

Yes No

6. Bleeding Symptoms

Have you noticed any unusual bleeding or bruising?

Yes No

Are you experiencing any other new symptoms?

Yes No

If yes, please specify:

7. Recent Medical Procedures

Have you undergone any medical or dental procedures recently?
Yes No

8. Ability to Attend Follow-Up

Are you able to come in for a follow-up INR test if needed?
Yes No

9. Other Relevant Questions

Do you have any history of liver or kidney disease?
Yes No

Have you had a history of bleeding disorders or previous significant bleeding episodes?
Yes No

Are you currently pregnant or breastfeeding (if applicable)?
Yes No

Have you had a recent infection or fever?
Yes No

Management -

Key Points

Stop warfarin if there is bleeding or significantly high INR.
Vitamin K1 (phytomenadione) reverses warfarin’s effect — route and dosage depend on severity of bleeding and INR.
Prothrombin complex concentrate (PCC) or fresh frozen plasma corrects coagulopathy urgently if major bleeding occurs.
Restart warfarin only when INR is back to a safer range (often <5).
Investigate any unexpected bleeding even if INR is at the therapeutic range.

Scenario	Action
Major Bleeding	Stop warfarin. Refer urgently for phytomenadione (vitamin K₁) IV. Give dried prothrombin complex concentrate or fresh frozen plasma if PCC is unavailable.
INR > 8 Minor Bleeding	Stop warfarin. Give vitamin K₁ by slow IV injection. Repeat the dose after 24 hours if INR remains too high. Restart warfarin when INR < 5.
INR > 8 No Bleeding	Stop warfarin. Give vitamin K₁ by oral route using IV preparation (off-label). Repeat the dose after 24 hours if INR remains too high. Restart warfarin when INR < 5.
INR 5–8 Minor Bleeding	Stop warfarin. Give vitamin K₁ by slow IV injection. Restart warfarin when INR < 5.
INR 5–8 No Bleeding	Withhold 1 or 2 doses of warfarin. Reduce the subsequent maintenance dose.
Unexpected Bleeding at Therapeutic INR	Always investigate for an underlying cause (e.g. GI tract pathology, renal issues).

Vitamin K (phytonadione) works by promoting the hepatic synthesis of vitamin K–dependent clotting factors (II, VII, IX, and X), thereby lowering the INR. Oral doses typically range from 1–5 mg, depending on how high the INR is and whether there is bleeding. Check the INR again in about 24 hours to assess response and determine if an additional dose is needed.

References

Fenta, T., Assefa, T., & Bekele, A. (2017). Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: A retrospective cross-sectional study. BMC Health Services Research, 17(1). https://doi.org/10.1186/s12913-017-2330-0
Ham, H., Klungel, O., Leufkens, H., & Staa, T. (2013). The patterns of anticoagulation control and the risk of stroke, bleeding and mortality in patients with non‐valvular atrial fibrillation. Journal of Thrombosis and Haemostasis, 11(1), 107–115. https://doi.org/10.1111/jth.12041
Kılıç, S. (2017). Comparison of warfarin use in terms of efficacy and safety in two different polyclinics. The Anatolian Journal of Cardiology. https://doi.org/10.14744/anatoljcardiol.2017.7886
Sekaggya, C., Nalwanga, D., Braun, A., Nakijoba, R., Kambugu, A., Fehr, J., … & Castelnuovo, B. (2016). Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: A case series. BMC Hematology, 16(1). https://doi.org/10.1186/s12878-016-0056-6
Türen, S., & Turen, S. (2022). Determination of factors affecting time in therapeutic range in patients on warfarin therapy. Biological Research for Nursing, 25(1), 170–178. https://doi.org/10.1177/10998004221127977
NICE Clinical Knowledge Summaries (CKS). (n.d.). Anticoagulation — oral: Warfarin. Retrieved from https://cks.nice.org.uk/topics/anticoagulation-oral/management/warfarin/