Bleeding and Thromboembolism During Anticoagulant Therapy:A Population-Based Study in Rochester, Minnesota

Gitter, Michael J.; Jaeger, Thomas M.; Petterson, Tanya M.; Gersh, Bernard J.; Silverstein, Marc D.

doi:10.4065/70.8.725

Cited by 250 publications

(178 citation statements)

References 18 publications

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“…Gitter et al, using Landefeld's bleeding severity index, estimated the cumulative incidence of major hemorrhage to be 5.3% at 1 year. 7 This was a marked decrease in the incidence of major hemorrhage from that in previous cohort studies. It is uncertain whether this decreased incidence reflects the recommendations for reduced intensity of warfarin treatment, or reflects baseline patient characteristics among this population-based sample.…”

mentioning

confidence: 63%

“…The major indication for treatment in Landefeld's study was cardiovascular surgery, while the primary indication for treatment in Gitter's study was venous thromboembolism, and the major cause for treatment in our study was atrial fibrillation. 4,7 Therefore, the target prothrombin ratios would have been higher for the majority of patients in Landefeld's study, and may be responsible for the increased incidence of hemorrhage in that population. Our reduced incidence of major hemorrhage is still higher than the majority of estimates reported in experimental studies.…”

Section: Incidence Of Major Hemorrhagementioning

confidence: 99%

“…This lower incidence of hemorrhage was similar to Gitter's estimate of major hemorrhage of 5.3% at 1 year. 7 The study type and criteria for major hemorrhage were the same for all three observational studies; therefore, the lower incidence of major hemorrhage in the cohorts assembled after 1989 may reflect the recommendation for reductions in the therapeutic ranges for patients receiving warfarin. However, the difference in the incidence of major hemorrhage may reflect the differences in the indications for warfarin therapy among the different studies.…”

Section: Incidence Of Major Hemorrhagementioning

confidence: 99%

“…This inconsistency has been attributed to the use of different populations as well as different criteria for major hemorrhage. 13 Landefeld and Goldman 4 and Gitter et al 7 identified different predictors for major hemorrhage, despite using the same criteria for major hemorrhage.…”

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confidence: 99%

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Risk of major hemorrhage for outpatients treated with warfarin

et al. 1998

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OBJECTIVE:To determine the incidence of major hemorrhage among outpatients started on warfarin therapy after the recommendation in 1986 for reduced-intensity anticoagulation therapy was made, and to identify baseline patient characteristics that predict those patients who will have a major hemorrhage. DESIGN:Retrospective cohort study. SETTING:A university-affiliated Veterans Affairs Medical Center. PATIENTS:Five hundred seventy-nine patients who were discharged from the hospital after being started on warfarin therapy. MEASUREMENTS AND MAIN RESULTS:The primary outcome variable was major hemorrhage. In our cohort of 579 patients, there were 40 first-time major hemorrhages with only one fatal bleed. The cumulative incidence was 7% at 1 year. The average monthly incidence of major hemorrhage was 0.82% during the first 3 months of treatment and decreased to 0.36% thereafter. Three independent predictors of major hemorrhage were identified: a history of alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed. Age, comorbidities, medications known to influence prothrombin levels, and baseline laboratory values were not associated with major hemorrhage. CONCLUSIONS:The incidence of major hemorrhage in this population of outpatients treated with warfarin was lower than previous estimates of major hemorrhage measured before the recommendation for reduced-intensity anticoagulation therapy was made, but still higher than estimates reported from clinical trials. Alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed were associated with increased risk of major hemorrhage.

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confidence: 63%

Section: Incidence Of Major Hemorrhagementioning

confidence: 99%

Section: Incidence Of Major Hemorrhagementioning

confidence: 99%

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confidence: 99%

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Risk of major hemorrhage for outpatients treated with warfarin

et al. 1998

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“…The most important risk factors associated with warfarin-related bleeding were advanced age, female sex, history of a gastrointestinal bleeding event, and comorbid conditions, such as hypertension, cerebrovascular disease, atrial fibrillation, heart disease, renal insufficiency, liver disease, and alcoholism. In a retrospective study of 261 patients with a median age of 69 years who began taking warfarin and continued receiving therapy for longer than 4 weeks in 1987-1989, Gitter et al 14 reported the incidence of warfarin-related bleeding at 8% per year of warfarin therapy and the incidence of thromboembolism at 3% per year of warfarin therapy. From…”

Section: Incidence Of Warfarin-related Adesmentioning

confidence: 99%

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Moyer

O’Kane

Baudhuin

et al. 2009

Mayo Clinic Proceedings

114

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ADE = adverse drug event; AEI = American Enterprise Institute; ASPE = allele-specific primer extension; CYP2C9 = cytochrome P450 2C9; INR = international normalized ratio; PCR = polymerase chain reaction; SNP = single-nucleotide polymorphism; VitKH 2 = vitamin K hydroquinone; VKOR = vitamin K epoxide reductase; VKORC1 = VKOR complex, subunit 1 W arfarin is a well-accepted therapy used for the prevention of stroke in patients with atrial fibrillation, for prophylaxis of venous thromboembolism and pulmonary embolism in patients with prosthetic heart valves and myocardial infarction, and for prevention of pulmonary embolism or deep venous thrombosis in patients undergoing orthopedic surgery or with a history of venous or arterial thromboembolism. Many reviews and clinical practice guidelines (summarized by Ansell et al, 1 Baglin et al, 2 Flockhart et al, 3 Husted et al, 4 and Singer et al 5 ) outline the substantial benefits of warfarin therapy for the prevention of strokes in these patients. The American Enterprise Institute (AEI)-Brookings Joint Center for Regulatory Studies Report, which reviewed the use of warfarin in the United States, estimates that approximately 2 million US citizens are prescribed warfarin annually. 6 In 2003, a total of 21.2 million prescriptions were written for oral warfarin in the United States. 7 Warfarin interferes with coagulation by inhibiting regeneration of the reduced form of vitamin K, a cofactor in the γ-glutamyl-carboxylase -mediated activation of coagulation factors II, VII, IX, and X ( Figure 1). The oxidized, inactive form of vitamin K is converted to the reduced form of vitamin K by vitamin K epoxide reductase (VKOR); warfarin inhibits VKOR, resulting in less of the reduced form of vitamin K available to support the factor carboxylation required to sustain the coagulation cascade. 8 Warfarin has a narrow therapeutic index that contributes either to therapeutic failure (potentially leading to stroke or other complications) or therapeutic excess (potentially leading to bleeding and hemorrhage). Many surveys have described the incidence of warfarin-related adverse drugThe antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to ach...

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Bleeding During Warfarin and Aspirin Therapy in Patients With Atrial Fibrillation

Gulløv

Koefoed²,

Petersen³

1999

Arch Intern Med

215

146

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Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding. The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy (INR, 2.0-3.0).

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Bleeding and Thromboembolism During Anticoagulant Therapy:A Population-Based Study in Rochester, Minnesota

Cited by 250 publications

References 18 publications

Risk of major hemorrhage for outpatients treated with warfarin

Risk of major hemorrhage for outpatients treated with warfarin

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Bleeding During Warfarin and Aspirin Therapy in Patients With Atrial Fibrillation

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