Predicting Risk for Prolonged High INR after Too Much Anticoagulation

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The summary below is from the full report titled "Clinical Predictors of Prolonged Delay in Return of the International Normalized Ratio to within the Therapeutic Range after Excessive Anticoagulation with Warfarin." It is in the 18 September 2001 issue of Annals of Internal Medicine (volume 135, pages 393-400). The authors are EM Hylek, S Regan, AS Go, RA Hughes, DE Singer, and SJ Skates.

What is the problem and what is known about it so far?

Warfarin is a drug that "thins the blood" by interfering with normal blood clotting (anticoagulation). It is given to prevent blood clots in the legs, lungs, heart, and brain. Patients who take warfarin need routine blood tests to see whether their blood is "too thin," a condition that can cause serious bleeding. The test that best measures warfarin's actions is the international normalized ratio (INR). Patients with too much anticoagulation have high INRs and high risk for bleeding. If the INR is greater than 5.0, warfarin treatment is often stopped for several days, or vitamin K₁ is given to counteract the effects of warfarin. However, vitamin K₁ may be unnecessary in some patients, and it can cause adverse effects. Deciding which patients need vitamin K₁ is not easy because it is difficult to know which patients will have prolonged abnormal INR values without vitamin K₁ treatment.

Why did the researchers do this particular study?

To identify factors that predict prolonged high INR values after too much anticoagulation.

Who was studied?

633 patients who were treated in an anticoagulant therapy unit between 1993 and 1998.

How was the study done?

The researchers reviewed medical records of patients who had been followed in their clinic for more than 60 days. They identified patients whose INRs went above 6.0 at some point and who then had repeated INR tests after warfarin treatment had been stopped for 2 days. No patient had received vitamin K₁. The researchers divided patients into those whose repeated INR tests suggested a prolonged risk (INR of 4.0 or greater) and those whose repeated tests no longer suggested such a risk (INR less than 4.0, a safer value).

What did the researchers find?

About one third of the patients had an INR of 4.0 or greater after warfarin treatment had been withheld for 2 days. Factors associated with a prolonged INR of 4.0 or greater were being older, having a higher INR when too much anticoagulation was first recognized, having unstable heart failure, having cancer that was metastatic or required chemotherapy, and needing small rather than large weekly doses of warfarin to maintain anticoagulation before the episode of too much anticoagulation.

What were the limitations of the study?

Study data were obtained from patients' records, which are sometimes incomplete. Although high INR is a marker for increased bleeding risk, many people with prolonged INRs of 4.0 or greater do not bleed. The study did not look at factors that predict actual bleeding.

What are the implications of the study?

Excessive anticoagulation is likely to last longest in patients who are older, have unstable heart failure or cancer, have higher INRs, and require smaller maintenance doses of warfarin. Reversal of too much anticoagulation with vitamin K₁ should be considered for such patients.