Consequences of Serious Bleeding Complications from Warfarin

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The summary below is from the full report titled "Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism. A Meta-Analysis." It is in the 2 December 2003 issue of Annals of Internal Medicine (volume 139, pages 893-900). The authors are L.A. Linkins, P.T. Choi, and J.D. Douketis.

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

Blood clots in the deep veins of the legs or pelvis are called deep venous thrombosis (DVT). These blood clots are dangerous because they can break free and travel to the lungs. This problem, called pulmonary embolism (clot in the lung), can be fatal. Doctors typically treat patients with DVT with blood-thinning drugs for 3 to 6 months. Some patients with high risks for repeated clots need even longer treatment. The blood-thinning drugs prevent the formation of new clots, reduce the risk that a clot will travel to the lungs, and prevent repeated clots. Doctors often use a powerful blood-thinning drug called warfarin to prevent repeated clots in patients with DVT. People taking this drug need frequent blood tests to make sure that the dose being given reduces the blood's tendency to clot, but not so much that bleeding occurs spontaneously. Even with careful monitoring, some patients who take warfarin have bleeding complications. The consequences of the bleeding complications aren't well known.

Why did the researchers do this particular study?

To describe the frequency and consequences of major bleeding in patients taking warfarin for DVT.

Who was studied?

10,757 patients from 33 studies.

How was the study done?

Rather than doing a new study, the researchers looked at previous studies that involved patients with DVT who were treated with warfarin-type drugs for at least 3 months. Patients in these studies weren't allowed to take other drugs, such as aspirin, that might affect blood clotting. Their doses of warfarin and clotting ability were monitored with particular blood tests (international normalized ratio targets of 2.0 to 3.0). The researchers summarized numbers of patients with major bleeding events that required hospitalization or a blood transfusion, numbers of patients with bleeding inside the skull (intracranial bleeding), and numbers of patients who died.

What did the researchers find?

Patients in the studies had 276 major bleeding events; 37 of these were fatal. Of 24 intracranial bleeding episodes, 11 were fatal. Risks for bleeding appeared highest within the first 3 months of starting warfarin. The summary estimated number of major bleeding events per 1000 patients taking warfarin for 1 year was 72. The summary estimated number of deaths from bleeding per 1000 patients taking warfarin for 1 year was 13.

What were the limitations of the study?

The reviewed studies used slightly different definitions of major bleeding events. Exact estimates of when bleeding occurred (for example, within 10 days of starting warfarin therapy) weren't possible because many studies did not report the time of each bleeding event.

What are the implications of the study?

Major bleeding events have serious consequences in people taking warfarin for DVT. About 1 in 8 people with major bleeding episodes die. Nearly 10% of major bleeding episodes are intracranial, and nearly 50% of these are fatal.