Volume 8, Number 1;  July 5, 2007

Patient:

Session Handout:

Readings:

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Unique Identifier [PMID]: 16475043

Authors: Kovacs MJ.

Institution: London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada. michael.kovacs@lhsc.on.ca

Title: The standard is still the standard or why an INR of 2-3 is still the optimal intensity for secondary prevention of venous thromboembolism.[comment].

Source: Journal of Thrombosis & Thrombolysis. 21(1):53-6, 2006 Feb.

Abstract: The optimal intensity of warfarin anticoagulation for secondary prevention of venous thromboembolism is debatable. Recent studies have shed light on the issue. The two pivotal studies, ELATE and PREVENT, are reviewed and discussed. Although the ELATE and PREVENT studies offer different conclusions, the results of the two studies are consistent with each other. Low intensity warfarin is more efficacious than placebo, although it is less efficacious than standard intensity and offers no safety advantage. For long term secondary prophylaxis of spontaneous venous thromboembolism, the optimal INR intensity of warfarin remains 2.0-3.0.

Publication Type: Comment. Comparative Study. Journal Article.

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Unique Identifier [PMID]: 11696471

Authors: Brummel KE. Paradis SG. Branda RF. Mann KG.

Institution: Department of Biochemistry, Given Building, Health Science Complex University of Vermont, College of Medicine, Burlington, USA.

Title: Oral anticoagulation thresholds.

Source: Circulation. 104(19):2311-7, 2001 Nov 6.

Abstract: BACKGROUND: Monitoring patients on oral anticoagulation is essential to prevent hemorrhage and recurrent thrombosis. We studied tissue factor-induced whole-blood coagulation in patients on warfarin therapy with similar international normalized ratios (INRs). METHODS AND RESULTS: Contact pathway-suppressed whole-blood coagulation initiated with tissue factor was studied in 8 male subjects (group W) and in 1 individual multiple times (subject A). Coagulation profiles for group W showed that subjects with similar INRs had widely varying clot times (6.2 to 23 minutes) and thrombin-antithrombin III (TAT) profiles with rates of 25 to 40 nmol. L(-1). min(-1) and maximum levels varying from 192 to 349 nmol/L. The normal control group exhibited clot times of 5.7+/-0.3 minutes and TAT rates of 57+/-13 nmol. L(-1). min(-1), reaching maximum levels of 742+/-91 nmol/L. Subject A, who was stably anticoagulated at an INR of 2.1+/-0.4 for 6 months, had widely ranging profiles with clot times of 9.0 to 22.7 minutes, TAT maximums varying from 141 to 345 nmol/L, and TAT formation rates of 10 to 57 nmol. L(-1). min(-1). INR did not correlate with TAT formation. Platelet activation was decreased by anticoagulants but also displayed variability. Fibrinopeptide A generation showed threshold variability independent of the INR. Factor VIII levels were increased (P=0.03) in group W (204+/-34.4%) compared with normal control subjects (149.4+/-37.4%). A significant correlation was identified between increasing factor VIII levels and years on warfarin therapy (r=0.78, P=0.01), suggesting a possible factor VIII compensatory mechanism. CONCLUSIONS: These results suggest that control of anticoagulation in patients to a set INR therapeutic range may be less secure than anticipated. Patients with similar INRs show significant individual variability in their tissue factor coagulation response, suggesting different risks to anticoagulation when confronted with underlying vascular anomalies.

Publication Type: Clinical Trial. Controlled Clinical Trial. Journal Article. Research Support, U.S. Gov't, P.H.S..

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Unique Identifier [PMID]: 11157640

Authors: Hirsh J. Dalen J. Anderson DR. Poller L. Bussey H. Ansell J. Deykin D.

Institution: Hamilton Civics Hospitals Research Centre, Ontario, Canada.

Title: Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. [Review] [163 refs]

Source: Chest. 119(1 Suppl):8S-21S, 2001 Jan.

Publication Type: Journal Article. Review.

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Unique Identifier [PMID]: 7776988

Authors: Cannegieter SC. Rosendaal FR. Wintzen AR. van der Meer FJ. Vandenbroucke JP. Briet E.

Institution: Department of Hematology, University Hospital Leiden, The Netherlands.

Title: Optimal oral anticoagulant therapy in patients with mechanical heart valves.[see comment].

Source: New England Journal of Medicine. 333(1):11-7, 1995 Jul 6.

Abstract: BACKGROUND. The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of anticoagulation. METHODS. Data were collected on all patients with mechanical heart valves who have been seen at four regional Dutch anticoagulation clinics since 1985. The primary outcome events were episodes of thromboembolism or major bleeding. The intensity-specific incidence of each type of event was calculated as the number of events that occurred at a certain intensity of anticoagulation (expressed in terms of the international normalized ratio [INR]) divided by the number of patient-years during which the INR was at this level in the total patient population. RESULTS. A total of 1608 patients were followed during 6475 patient-years. Cerebral embolism occurred in 43 patients (0.68 per 100 patient-years) and peripheral embolism in 2 (0.03 per 100 patient-years). Intracranial and spinal bleeding occurred in 36 patients (0.57 per 100 patient-years) and major extracranial bleeding in 128 (2.1 per 100 patient-years). The optimal intensity of anticoagulation, at which the incidence of both complications was lowest, was achieved when the INR was between 2.5 and 4.9. CONCLUSIONS. The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended.

Publication Type: Journal Article. Multicenter Study. Research Support, Non-U.S. Gov't.

Resident Report / Department of Medicine & Grady Branch Library

Emory University School of Medicine

2007 Edition

Participating Faculty:  Carlos Del Rio MD  / Joyce Doyle MD / Lorenzo Difrancesco MD / Rachel Del Favero MD / Lewis Satterwhite  MD

Contact: Karl Woodworth