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Bleeding Complications in Oral Anticoagulant Therapy: An Analysis of Risk Factors

Bleeding Complications in Oral Anticoagulant Therapy: An Analysis of Risk Factors Abstract Background: Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. Methods: In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. Results: Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age <40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. Conclusions: The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.(Arch Intern Med. 1993;153:1557-1562) References 1. Hirsh J. Oral anticoagulant drugs . N Engl J Med. 1991;324:1865-1875.Crossref 2. Hirsh J, Levine M. Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America . Thromb Haemost. 1988;59:129-132. 3. Loeliger EA, van Dijk-Wierda CA, van den Besselaar AMHP, Broekmans AW, Roos J. Anticoagulant control and the risk of bleeding . In: Meade TW, ed. Anticoagulants and Myocardial Infarction: A Reappraisal . New York, NY: John Wiley & Sons Inc; 1984:135-177. 4. van den Besselaar AMHP, van der Meer FJM, Gerrits-Drabbe CW. Therapeutic control of oral anticoagulant treatment in the Netherlands . Am J Clin Pathol. 1988;90:685-690. 5. Wiegman H, Vossepoel AM. A computer program for long term anticoagulation control . Comput Methods Programs Biomed. 1977;7:71-84.Crossref 6. Zucker S, Cathey MH, Sox PJ, Hall EC. Standardization of laboratory tests for controlling anticoagulant therapy . Am J Clin Pathol. 1970;53:348-354. 7. Rosendaal FR, Cannegieter SC, van der Meer FJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy . Thromb Haemost. 1993;69: 236-239. 8. Sixty Plus Reinfarction Study Research Group. A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction: report of the Sixty Plus Reinfarction Study Research Group . Lancet. 1980;2:989-994. 9. Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction: second report of the Sixty Plus Reinfarction Study Research Group . Lancet. 1982;1:64-68. 10. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction . N Engl J Med. 1990;323:147-152.Crossref 11. Petersen P, Godtfredsen J, Boysen G, Andersen ED, Andersen B. Placebocontrolled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study . Lancet. 1989;1:175-179.Crossref 12. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation . N Engl J Med. 1990;323:1505-1511.Crossref 13. Petitti DB, Strom BL, Melmon KL. Duration of warfarin anticoagulant therapy and the probabilities of recurrent thromboembolism and hemorrhage . Am J Med. 1986;81:255-259.Crossref 14. Gurwitz JH, Goldberg RJ, Holden A, Knapic N, Ansell J. Age-related risks of long-term oral anticoagulant therapy . Arch Intern Med. 1988;148:1733-1736.Crossref 15. Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start start of outpatient therapy . Am J Med. 1989;87:144-152.Crossref 16. Forfar JC. A 7-year analysis of haemorrhage in patients on long-term anticoagulant treatment . Br Heart J. 1979;42:128-132.Crossref 17. Petty GW, Lennihan L, Mohr JP, et al. Complications of long-term anticoagulation . Ann Neurol. 1988;23:570-574.Crossref 18. Launbjerg J, Egeblad H, Heaf J, Nielsen NH, Fugleholm AM, Ladefoged K. Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment years in 551 outpatients . J Intern Med. 1991;229:351-355.Crossref 19. Moschos CB, Wong PCY, Sise HS. Controlled study of the effective level of long-term anticoagulation . JAMA. 1964;190:799-805.Crossref 20. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis . N Engl J Med. 1982;307:1676-1681.Crossref 21. Turpie AGG, Hirsh J, Gunstensen J, Nelson H, Gent M. Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement . Lancet. 1988;1:1242-1245.Crossref 22. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions . Am J Med. 1989;87:153-159.Crossref 23. Saour JL, Sieck JO, Mamo LAR, Gallus AS. Trial of different intensities of anticoagulation in patients with prosthetic heart valves . N Engl J Med. 1990;322: 428-432.Crossref 24. Lundstrom T, Ryden L. Haemorrhagic and thromboembolic complications in patients with atrial fibrillation on anticoagulant prophylaxis . J Intern Med. 1989; 225:137-142.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Bleeding Complications in Oral Anticoagulant Therapy: An Analysis of Risk Factors

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References (26)

Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1993.00410130073007
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. Methods: In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. Results: Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age <40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. Conclusions: The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.(Arch Intern Med. 1993;153:1557-1562) References 1. Hirsh J. Oral anticoagulant drugs . N Engl J Med. 1991;324:1865-1875.Crossref 2. Hirsh J, Levine M. Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America . Thromb Haemost. 1988;59:129-132. 3. Loeliger EA, van Dijk-Wierda CA, van den Besselaar AMHP, Broekmans AW, Roos J. Anticoagulant control and the risk of bleeding . In: Meade TW, ed. Anticoagulants and Myocardial Infarction: A Reappraisal . New York, NY: John Wiley & Sons Inc; 1984:135-177. 4. van den Besselaar AMHP, van der Meer FJM, Gerrits-Drabbe CW. Therapeutic control of oral anticoagulant treatment in the Netherlands . Am J Clin Pathol. 1988;90:685-690. 5. Wiegman H, Vossepoel AM. A computer program for long term anticoagulation control . Comput Methods Programs Biomed. 1977;7:71-84.Crossref 6. Zucker S, Cathey MH, Sox PJ, Hall EC. Standardization of laboratory tests for controlling anticoagulant therapy . Am J Clin Pathol. 1970;53:348-354. 7. Rosendaal FR, Cannegieter SC, van der Meer FJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy . Thromb Haemost. 1993;69: 236-239. 8. Sixty Plus Reinfarction Study Research Group. A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction: report of the Sixty Plus Reinfarction Study Research Group . Lancet. 1980;2:989-994. 9. Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction: second report of the Sixty Plus Reinfarction Study Research Group . Lancet. 1982;1:64-68. 10. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction . N Engl J Med. 1990;323:147-152.Crossref 11. Petersen P, Godtfredsen J, Boysen G, Andersen ED, Andersen B. Placebocontrolled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study . Lancet. 1989;1:175-179.Crossref 12. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation . N Engl J Med. 1990;323:1505-1511.Crossref 13. Petitti DB, Strom BL, Melmon KL. Duration of warfarin anticoagulant therapy and the probabilities of recurrent thromboembolism and hemorrhage . Am J Med. 1986;81:255-259.Crossref 14. Gurwitz JH, Goldberg RJ, Holden A, Knapic N, Ansell J. Age-related risks of long-term oral anticoagulant therapy . Arch Intern Med. 1988;148:1733-1736.Crossref 15. Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start start of outpatient therapy . Am J Med. 1989;87:144-152.Crossref 16. Forfar JC. A 7-year analysis of haemorrhage in patients on long-term anticoagulant treatment . Br Heart J. 1979;42:128-132.Crossref 17. Petty GW, Lennihan L, Mohr JP, et al. Complications of long-term anticoagulation . Ann Neurol. 1988;23:570-574.Crossref 18. Launbjerg J, Egeblad H, Heaf J, Nielsen NH, Fugleholm AM, Ladefoged K. Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment years in 551 outpatients . J Intern Med. 1991;229:351-355.Crossref 19. Moschos CB, Wong PCY, Sise HS. Controlled study of the effective level of long-term anticoagulation . JAMA. 1964;190:799-805.Crossref 20. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis . N Engl J Med. 1982;307:1676-1681.Crossref 21. Turpie AGG, Hirsh J, Gunstensen J, Nelson H, Gent M. Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement . Lancet. 1988;1:1242-1245.Crossref 22. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions . Am J Med. 1989;87:153-159.Crossref 23. Saour JL, Sieck JO, Mamo LAR, Gallus AS. Trial of different intensities of anticoagulation in patients with prosthetic heart valves . N Engl J Med. 1990;322: 428-432.Crossref 24. Lundstrom T, Ryden L. Haemorrhagic and thromboembolic complications in patients with atrial fibrillation on anticoagulant prophylaxis . J Intern Med. 1989; 225:137-142.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jul 12, 1993

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