PREDICTORS OF MAJOR BLEEDING AMONG ATRIAL FIBRILLATION PATIENTS ON WARFARIN

  • LAILA M MATALQAH Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan.
  • ALAA YEHYA Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
  • GHAITH M AL-TAANI Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.

Abstract

Objective: Bleeding is the most serious complication associated with anticoagulation therapy. The purpose of this study was to estimate the frequency of major bleeding related to warfarin and to identify its predictors in patients with atrial fibrillation (AF).


Methods: Patients with AF treated with warfarin at Penang General Hospital in Malaysia were identified according to the international classification of disease, Ninth Revision, Clinical Modification (ICD-9). The medical reports of 1611 patients were reviewed, bleeding events were set as primary end point which were identified in 313 patients. Demographic and clinical data were retrieved and warfarin therapy-related parameters including dose, therapy duration, and prothrombin time-international normalized ratio (PT-INR) were recorded and analyzed using descriptive statistics.


Results: Of the 313 patients, 28 patients with major bleeding events were identified. Gastrointestinal bleeding was the major type of bleeding, which accounts for 68% (n = 17) of the cases. The frequency of major bleeding events among all AF patients was 1.7%. High PT-INR value was found in 96.3% (n = 28) of the patients, thereby making it the primary predictor of bleeding events. Other predictors including, advanced age, other comorbidities such as hypertension and multiple anticoagulation therapy were also observed to be significant.


Conclusion: Lower doses of warfarin are recommended to achieve target PT-INR range similar to that reported previously for Asian populations. A regular clinical review for bleeding predictors is essential for maximizing the time spent by the patient taking warfarin in the optimal therapeutic range and for making recommended therapy adjustment.

Keywords: Major bleeding, Warfarin, Atrial fibrillation, Anticoagulants, Malaysian patients.

References

1. Xu J, Luc JG, Phan K. Atrial fibrillation: Review of current treatment strategies. J Thorac Dis 2016;8:E886-E900.
2. Katritsis DG, Gersh BJ, Camm AJ. Anticoagulation in atrial fibrillation - current concepts. Arrhythm Electrophysiol Rev 2015;4:100-7.
3. Senoo K, Lane D, Lip GY. Stroke and bleeding risk in atrial fibrillation. Korean Circ J 2014;44:281-90.
4. Mittal MK, Rabinstein AA. Anticoagulation-related intracranial hemorrhages. Curr Atheroscler Rep 2012;14:351-9.
5. Hughes M, Lip GY, Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: A systematic review. QJM 2007;100:599-607.
6. Healey JS, Oldgren J, Ezekowitz M, Zhu J, Pais P, Wang J, et al. Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: A cohort study. Lancet 2016;388:1161- 9.
7. Steinberg BA, Piccini JP. Anticoagulation in atrial fibrillation. BMJ 2014;348:g2116.
8. Kuruvilla M, Gurk-Turner C. A review of warfarin dosing and monitoring. Proc (Bayl Univ Med Cent) 2001;14:305-6.
9. Roskell NS, Samuel M, Noack H, Monz BU. Major bleeding in patients with atrial fibrillation receiving Vitamin K antagonists: A systematic review of randomized and observational studies. Europace 2013;15:787- 97.
10. Suzuki S, Yamashita T, Kato T, Fujino T, Sagara K, Sawada H, et al. Incidence of major bleeding complication of warfarin therapy in japanese patients with atrial fibrillation. Circ J 2007;71:761-5.
11. Guo Y, Lip GY, Apostolakis S. The unmet need of stroke prevention in atrial fibrillation in the far east and South East Asia. Malays J Med Sci 2012;19:1-7.
12. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692-4.
13. Chen JY, Zhang AD, Lu HY, Guo J, Wang FF, Li ZC, et al. CHADS2 versus CHA2DS2-VASc score in assessing the stroke and thromboembolism risk stratification in patients with atrial fibrillation: A systematic review and meta-analysis. J Geriatr Cardiol 2013;10:258- 66.
14. Mitine C, Leunens G, Verstraete J, Blanckaert N, Van Dam J, Dutreix A, et al. Is it necessary to repeat quality control procedures for head and neck patients? Radiother Oncol 1991;21:201-10.
15. Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, Gornick CC, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans affairs stroke prevention in nonrheumatic atrial fibrillation investigators. N Engl J Med 1992;327:1406-12.
16. Barcellona D, Contu P, Marongiu F. Patient education and oral anticoagulant therapy. Haematologica 2002;87:1081-6.
17. Taylor FC, Ramsay ME, Tan G, Gabbay J, Cohen H. Evaluation of patients’ knowledge about anticoagulant treatment. Qual Health Care 1994;3:79-85.
18. Greenblatt DJ, von Moltke LL. Interaction of warfarin with drugs, natural substances, and foods. J Clin Pharmacol 2005;45:127-32.
19. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005;165:1095-106.
20. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 2001;119:108S-121S.
21. Michael S, Sobel MS. Anticoagulants: To bleed or not to bleed, that is the question. Semin Vasc Surg 2002;15:256-67.
22. Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: Clinical epidemiology, prediction, and prevention. Am J Med 1993;95:315-28.
23. 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;105:91-9.
24. McBride R. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449-57.
25. Choudari CP, Palmer KR. Acute gastrointestinal haemorrhage in patients treated with anticoagulant drugs. Gut 1995;36:483-4.
26. Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW, et al. Clinical classification schemes for predicting hemorrhage: Results from the national registry of atrial fibrillation (NRAF). Am Heart J 2006;151:713-9.
27. Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE trial (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation): Predictors, characteristics, and clinical outcomes. J Am Coll Cardiol 2014;63:2141-7.
28. Blin P, Dureau-Pournin C, Lassalle R, Abouelfath A, Droz-Perroteau C, Moore N, et al. A population database study of outcomes associated with Vitamin K antagonists in atrial fibrillation before DOAC. Br J Clin Pharmacol 2016;81:569-78.
29. Hollowell J, Ruigómez A, Johansson S, Wallander MA, García-Rodríguez LA. The incidence of bleeding complications associated with warfarin treatment in general practice in the United Kingdom. Br J Gen Pract 2003;53:312-4.
30. Lewison G, Kumar S, Wong CY, Roe P, Webber R. The contribution of ethnic groups to Malaysian scientific output, 1982-2014, and the effects of the new economic policy. Scientometrics 2016;109:1877-93.
31. Fang MC, Go AS, Hylek EM, Chang Y, Henault LE, Jensvold NG, et al. Age and the risk of warfarin-associated hemorrhage: The anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006;54:1231-6.
32. Torn M, Bollen WL, van der Meer FJ, van der Wall EE, Rosendaal FR. Risks of oral anticoagulant therapy with increasing age. Arch Intern Med 2005;165:1527-32.
33. Kuijer PM, Hutten BA, Prins MH, Büller HR. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999;159:457-60.
34. Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003;349:631-9.
35. Laupacis A, Boysen G, Connolly S, Ezekowitz M. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke prevention in atrial fibrillation II study. Lancet 1994;343:687-91.
36. Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH, et al. The risk for and severity of bleeding complications in elderly patients treated with warfarin. The national consortium of anticoagulation clinics. Ann Intern Med 1996;124:970-9.
37. Fitzmaurice DA, Blann AD, Lip GY. Bleeding risks of antithrombotic therapy. BMJ 2002;325:828-31.
38. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA 3rd, et al 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): A report of the american college of cardiology foundation/American heart association task force on practice guidelines. Circulation 2011;123:104- 23.
39. Lin KJ, Hernández-Díaz S, García Rodríguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology 2011;141:71-9.
40. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: The task force for the management of atrial fibrillation of the European society of cardiology (ESC). Europace 2010;12:1360-420.
41. Mallick KK. Common causes of gastrointestinal bleeding diagnosed by endoscopy/colonoscopy at hospital Sultanah Bahiyah, Alor Setar, Malaysia. IIOSR J Dent Med Sci 2014;13:36-41.
42. Teklay G, Shiferaw N, Legesse B, Bekele ML. Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: A prospective observational study. Thromb J 2014;12:20.
43. George RM, James E, Vijayalakshmi S. Clinical pharmacist’s interventions on drug related problems in a tertiary care hospital. Int J Pharm Pharm Sci 2015;7:401-4.
44. Cheema E, Singer DR. Community pharmacist-led new medicine service for patients with a long term medical condition: A cross-sectional study. Int J Pharm Pharm Sci 2017;9:129-33.
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How to Cite
M MATALQAH, L., A. YEHYA, and G. M. AL-TAANI. “PREDICTORS OF MAJOR BLEEDING AMONG ATRIAL FIBRILLATION PATIENTS ON WARFARIN”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 547-50, https://innovareacademics.in/journals/index.php/ajpcr/article/view/29955.
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