Point-of-Care Guides

Predicting the Risk of Bleeding in Patients Taking Warfarin

Am Fam Physician. 2010 Mar 15;81(6):780-782.

Clinical Question

What is the best way to predict the risk of bleeding in patients taking warfarin (Coumadin)?

Evidence Summary

When considering anticoagulation therapy in patients with atrial fibrillation or venous thromboembolism (VTE), physicians and patients must balance the benefits of anticoagulation with the risk of bleeding, particularly major bleeding complications. For example, in patients who are at high risk of bleeding, physicians may wish to consider aspirin instead of warfarin, especially if the risk of stroke or recurrent VTE is relatively low.

The Outpatient Bleeding Risk Index (OBRI; Table 113 ) is one of several models that have been developed to predict the risk of bleeding with warfarin (Table 215). The OBRI, which assigns one point for each of four variables, was developed in a population of 556 patients with VTE who were discharged on warfarin therapy.1 It was validated in a similar group of 264 patients.1 The OBRI was a good predictor of bleeding risk in the initial study and in two subsequent validation studies,2,3 but a more recent and larger study found it less helpful in identifying patients at high risk of major bleeding.5 However, this study did not include data for patients with renal impairment, and because all patients were 65 years or older (two of the four variables), the score could not be fully calculated.

Table 1.

Outpatient Bleeding Risk Index

Variable Points

65 years or older

1

History of stroke

1

History of gastrointestinal bleeding

1

Recent myocardial infarction, severe anemia, diabetes mellitus, or renal impairment*

1

Total points: _____

Points Major bleeding at one year
Beyth, 19981 Wells, 20032 Aspinall, 20053

Low risk: 0

3%

0%

0.8%

Intermediate risk: 1 or 2

12%

4.3%

2.5%

High risk: 3 or more

48%

Not applicable†

10.6%


*—Anemia is defined as hematocrit level < 30%, and renal impairment is defined as serum creatinine level > 1.5 mg per dL (133 μmol per L).

—Only two patients in this risk group.

Adapted with permission from Aspinall SL, DeSanzo BE, Trilli LE, Good CB. Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med. 2005;20(11):1009, with additional information from references 1 and 2.

Table 1.   Outpatient Bleeding Risk Index

View Table

Table 1.

Outpatient Bleeding Risk Index

Variable Points

65 years or older

1

History of stroke

1

History of gastrointestinal bleeding

1

Recent myocardial infarction, severe anemia, diabetes mellitus, or renal impairment*

1

Total points: _____

Points Major bleeding at one year
Beyth, 19981 Wells, 20032 Aspinall, 20053

Low risk: 0

3%

0%

0.8%

Intermediate risk: 1 or 2

12%

4.3%

2.5%

High risk: 3 or more

48%

Not applicable†

10.6%


*—Anemia is defined as hematocrit level < 30%, and renal impairment is defined as serum creatinine level > 1.5 mg per dL (133 μmol per L).

—Only two patients in this risk group.

Adapted with permission from Aspinall SL, DeSanzo BE, Trilli LE, Good CB. Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med. 2005;20(11):1009, with additional information from references 1 and 2.

Table 2.

Decision Rules to Predict Bleeding Risk in Patients Taking Warfarin (Coumadin)

Study Participants and indications Demographics Prediction of major bleeding by risk group

Beyth, 1998 (n = 820)1

Patients discharged on warfarin therapy (VTE, 47%; cardiac surgery, 18%; other, 35%)

Mean age = 60 years; 53% women

One-year bleeding risk using OBRI:

Low risk: 3%

Intermediate risk: 12%

High risk: 48%

Kuijer, 1999 (n = 1,021)4

Patients discharged on warfarin therapy after diagnosis of VTE

Mean age = 61 years; 51% men

90-day bleeding risk:

Low risk: 1%

High risk: 7%

Wells, 2003 (n = 222)2

Pulmonary embolism or deep venous thrombosis; started on low-molecular-weight heparin as outpatients and then switched to warfarin

Mean age = 58 years; 43% women

Bleeding risk per person-year using OBRI:

Low risk: 0%

Intermediate risk: 4.3%

High risk: not applicable*

Aspinall, 2005 (n = 1,269)3

Patients treated with warfarin at a Veterans Affairs anticoagulation clinic

Mean age = 68 years; 92% men

Bleeding risk per person-year using OBRI:

Low risk: 0.8%

Intermediate risk: 2.5%

High risk: 10.6%

Shireman, 2006 (n = 26,345)5

Registry of patients hospitalized with atrial fibrillation and discharged on warfarin therapy

All 65 years or older (88% 70 years or older); 53% women

90-day bleeding risk

Shireman rule:

Low risk: 0.9%

Intermediate risk: 2.0%

High risk: 5.4%

Intermediate- plus high-risk: 2.3%

OBRI†:

Intermediate risk: 1.0%

High risk: 2.5%

Kuijer rule:

Intermediate risk: 1.5%

High risk: 1.8%


OBRI = Outpatient Bleeding Risk Index; VTE = venous thromboembolism.

*— Only two patients in high-risk group.

†— Because all patients were 65 years or older, all were at intermediate or high risk. No data were available for patients with renal impairment, one of the four variables in the OBRI.

Information from references 1 through 5.

Table 2.   Decision Rules to Predict Bleeding Risk in Patients Taking Warfarin (Coumadin)

View Table

Table 2.

Decision Rules to Predict Bleeding Risk in Patients Taking Warfarin (Coumadin)

Study Participants and indications Demographics Prediction of major bleeding by risk group

Beyth, 1998 (n = 820)1

Patients discharged on warfarin therapy (VTE, 47%; cardiac surgery, 18%; other, 35%)

Mean age = 60 years; 53% women

One-year bleeding risk using OBRI:

Low risk: 3%

Intermediate risk: 12%

High risk: 48%

Kuijer, 1999 (n = 1,021)4

Patients discharged on warfarin therapy after diagnosis of VTE

Mean age = 61 years; 51% men

90-day bleeding risk:

Low risk: 1%

High risk: 7%

Wells, 2003 (n = 222)2

Pulmonary embolism or deep venous thrombosis; started on low-molecular-weight heparin as outpatients and then switched to warfarin

Mean age = 58 years; 43% women

Bleeding risk per person-year using OBRI:

Low risk: 0%

Intermediate risk: 4.3%

High risk: not applicable*

Aspinall, 2005 (n = 1,269)3

Patients treated with warfarin at a Veterans Affairs anticoagulation clinic

Mean age = 68 years; 92% men

Bleeding risk per person-year using OBRI:

Low risk: 0.8%

Intermediate risk: 2.5%

High risk: 10.6%

Shireman, 2006 (n = 26,345)5

Registry of patients hospitalized with atrial fibrillation and discharged on warfarin therapy

All 65 years or older (88% 70 years or older); 53% women

90-day bleeding risk

Shireman rule:

Low risk: 0.9%

Intermediate risk: 2.0%

High risk: 5.4%

Intermediate- plus high-risk: 2.3%

OBRI†:

Intermediate risk: 1.0%

High risk: 2.5%

Kuijer rule:

Intermediate risk: 1.5%

High risk: 1.8%


OBRI = Outpatient Bleeding Risk Index; VTE = venous thromboembolism.

*— Only two patients in high-risk group.

†— Because all patients were 65 years or older, all were at intermediate or high risk. No data were available for patients with renal impairment, one of the four variables in the OBRI.

Information from references 1 through 5.

Another model that uses only three variables (60 years or older, female sex, and presence of malignancy) predicts 90-day bleeding risks of 1 percent in low-risk patients and 7 percent in high-risk patients.4 However, this rule was not validated in a larger, more recent study,5 and does not include important risk factors such as anemia, history of bleeding, or use of antiplatelet agents. Therefore, it cannot be recommended for clinical use.

Most recently, Shireman and colleagues developed a new prediction model using 19,875 patients hospitalized with atrial fibrillation and discharged on warfarin therapy.5 The multivariate model was validated in 6,470 patients.5  It has eight clinical variables and identifies groups at low, intermediate, and high risk of major bleeding within 90 days of hospital discharge (Table 3).5 The Shireman model has good face validity, and because it was developed and validated in a large group of patients, it can distinguish between recent and remote bleeding, and can account for concurrent use of antiplate-let agents. However, as with the OBRI, only a small percentage of patients are identified as high risk (3.4 percent). When the intermediate- and high-risk groups are combined, two groups are created (low- and intermediate/high-risk) with bleeding risks of 0.9 and 2.3 percent, respectively. These results are remarkably similar to the 90-day risks found in the same study when it evaluated the OBRI (1.0 percent for intermediate risk, and 2.5 percent for high risk). Thus, these rules provide similar results. The difference between 1 and 2.5 percent over 90 days seems small, but becomes more significant over time as large numbers of patients (especially those with atrial fibrillation) are on anticoagulation therapy for many years.

Table 3.

Shireman Rule to Predict Bleeding Risk in Older Patients Taking Warfarin (Coumadin)

Variable Points

Anemia

86

Alcohol or drug abuse

71

Recent bleeding

62

Remote bleeding

58

70 years or older

49

Female sex

32

Antiplatelet use (e.g., aspirin, clopidogrel [Plavix])

32

Diabetes mellitus

27

Total points:

______

Score


Risk of major bleeding at 90 days


Low risk: < 108

0.9% (35 / 3,889)

Intermediate risk: 108 to 218

2.0% (48 / 2,400)

High risk: > 218

5.4% (12 / 222)

Intermediate/high risk combined

2.3% (60 / 2,622)


note: The original score was presented as an equation with factors between 0 and 1.0. Factors have been multiplied by 100 to create whole numbers and an additive score. The denominator for major bleeding was calculated from the percentage and numerator, because it was not reported in the original article.

Information from reference 5.

Table 3.   Shireman Rule to Predict Bleeding Risk in Older Patients Taking Warfarin (Coumadin)

View Table

Table 3.

Shireman Rule to Predict Bleeding Risk in Older Patients Taking Warfarin (Coumadin)

Variable Points

Anemia

86

Alcohol or drug abuse

71

Recent bleeding

62

Remote bleeding

58

70 years or older

49

Female sex

32

Antiplatelet use (e.g., aspirin, clopidogrel [Plavix])

32

Diabetes mellitus

27

Total points:

______

Score


Risk of major bleeding at 90 days


Low risk: < 108

0.9% (35 / 3,889)

Intermediate risk: 108 to 218

2.0% (48 / 2,400)

High risk: > 218

5.4% (12 / 222)

Intermediate/high risk combined

2.3% (60 / 2,622)


note: The original score was presented as an equation with factors between 0 and 1.0. Factors have been multiplied by 100 to create whole numbers and an additive score. The denominator for major bleeding was calculated from the percentage and numerator, because it was not reported in the original article.

Information from reference 5.

There are potentially important differences between the two models. Although the Shireman model was developed and validated in a large population, it is somewhat complex to calculate and is limited to patients 65 years or older with atrial fibrillation.5 The OBRI is simpler and has been validated in patients with atrial fibrillation or VTE, and in younger patients.13 Either rule can be used confidently—in combination with predictors of the risk of stroke or recurrent VTE—to help make decisions about the treatment strategy that best balances potential benefits and harms.

Mark H. Ebell, MD, MS, is associate professor in the Department of Epidemiology and Biostatistics in the College of Public Health at the University of Georgia, Athens.

Address correspondence to ebell@uga.edu. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med. 1998;105(2):91–99.

2. Wells PS, Forgie MA, Simms M, et al. The Outpatient Bleeding Risk Index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. Arch Intern Med. 2003;163(8):917–920.

3. Aspinall SL, DeSanzo BE, Trilli LE, Good CB. Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med. 2005;20(11):1008–1013.

4. Kuijer PM, Hutten BA, Prins MH, Büller HR. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med. 1999;159(5):457–460.

5. Shireman TI, Mahnken JD, Howard PA, Kresowik TF, Hou Q, Ellerbeck EF. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest. 2006;130(5):1390–1396.

This guide is one in a series that offers evidence-based tools to assist family physicians in improving their decision making at the point of care.

A collection of Point-of-Care Guides published in AFP is available at http://www.aafp.org/afp/poc.


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