Research Article
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Investigation of warfarin overdose and related factors in the emergency department

Year 2024, Volume: 10 Issue: 5, 513 - 521, 04.09.2024
https://doi.org/10.18621/eurj.1524168

Abstract

Objectives: This study aims to analyze the clinical features, symptoms, laboratory findings, and treatment approaches of patients presenting to the emergency department with elevated INR due to warfarin overdose.

Methods: The study was conducted retrospectively from August 1, 2023, to June 1, 2024, in the emergency department of a tertiary hospital in a city with a population of 5 million. Patients aged 18 and over with an INR value of 3.5 or above were included. Data were obtained from electronic health records and patient files. Statistical analyses were performed using IBM SPSS Statistics.

Results: A total of 121 patients were included in the study. The mean age was 71.85±12.28 years, with 53.7% female and 46.3% male. The most common diagnoses were atrial fibrillation (33.1%) and valve replacement (31.4%). The main reasons for emergency admission included general condition disorder (22.3%) and abdominal pain (16.5%). The bleeding rate was 47.9%, with the gastrointestinal system being the most common bleeding site (49.2%). The mean INR value was 9.27±5.45. Vitamin K was administered to 47.1% of patients and fresh frozen plasma to 28.1%. The discharge rate was 38.8%, and the mortality rate was 2.5%.

Conclusions: Patients presenting to the emergency department with warfarin overdose are at significant risk of severe bleeding, requiring careful management. Close monitoring and accurate dose adjustments are essential, especially in elderly and comorbid patients. Antidotes such as vitamin K, fresh frozen plasma, and prothrombin complex are effective in managing bleeding complications. Future studies should aim to standardize and enhance the effectiveness of these treatment protocols.

Ethical Statement

This study was approved by the Izmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee (Decision no.: 0337, Date: 20.07.2023).

References

  • 1. Aleksandrov A, Mirkov I, Ninkov M, et al. Effects of warfarin on biological processes other than haemostasis: A review. Food Chem Toxicol. 2018;113:19-32. doi:10.1016/j.fct.2018.01.019.
  • 2. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies. Chest. 2016;149(4):951-959. doi: 10.1378/chest.15-1719.
  • 3. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541-544. doi: 10.1038/nature02254.
  • 4. Ma Z, Wang P, Gao Z, Wang R, Khalighi K. Ensemble of machine learning algorithms using the stacked generalization approach to estimate the warfarin dose. PLoS One. 2018;13(10):e0205872. doi: 10.1371/journal.pone.0205872.
  • 5. Remijn JA, Lucas S, Wildeboer B, van Suijlen JD, Adriaansen HJ. Strongly increased international normalized ratio with recombinant Neoplastin R compared with tissue extract Neoplastin Plus in patients initiating oral anticoagulant therapy: implications for anticoagulation dosage. Clin Chem. 2008;54(11):1929-1931. doi: 10.1373/clinchem.2008.111336.
  • 6. Li S, Liu S, Liu XR, Zhang MM, Li W. Competitive tight-binding inhibition of VKORC1 underlies warfarin dosage variation and antidotal efficacy. Blood Adv. 2020;4(10):2202-2212. doi: 10.1182/bloodadvances.2020001750.
  • 7. Isbister GK, Hackett LP, Whyte IM. Intentional warfarin overdose. Ther Drug Monit. 2003;25(6):715-722. doi: 10.1097/00007691-200312000-00010.
  • 8. Shendre A, Parmar GM, Dillon C, Beasley TM, Limdi NA. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy. 2018;38(6):588-596. doi: 10.1002/phar.2089.
  • 9. Leiss W, Méan M, Limacher A, et al. Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism. J Gen Intern Med. 2015;30(1):17-24. doi:10.1007/s11606-014-2993-8.
  • 10. Atmaca Temrel T, Şahin S, Şan İ. What Is The Success Rate of Patients Using Warfarin In Maintaining Their Target International Normalized Ratio Levels? Ankara Med J. 2019;19(2):366-374. doi:10.17098/amj.577304.
  • 11. Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990.
  • 12. Panch SR, Savani BN, Stroncek DF. Transfusion Support in Patients with Hematologic Disease: New and Novel Transfusion Modalities. Semin Hematol. 2019;56(4):227-228. doi:10.1053/j.seminhematol.2019.11.007.
  • 13. Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. 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(11):970-979. doi: 10.7326/0003-4819-124-11-199606010-00004.
  • 14. Zapata L, Hansten P, Panic J, et al. Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592.
  • 15. Leonard C, Brensinger C, Bilker W, et al. Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics. Int J Cardiol. 2017;228:761-770. doi:10.1016/j.ijcard.2016.11.245.
  • 16. Erdoğan M, Ayhan H, Çolak Ş, et al. Epidemiological features of warfarin overdose and efficacy of prothrombin complex concentrates. J Exp Clin Med. 2014;30(4):327-330. doi:10.5835/jecm.omu.30.04.009.
  • 17. Costa-Lima C, Fiusa MM, Annichino-Bizzacchi JM, de Paula EV. Prothrombin complex concentrates in warfarin anticoagulation reversal. Rev Bras Hematol Hemoter. 2012;34(4):302-304. doi:10.5581/1516-8484.20120076.
  • 18. Güven O, Demireller M. Emergency department admissions and hemorrhage risk in patients on warfarin-containing drugs: a retrospective study. Northwestern Med J. 2024;4(1):41-47. doi:10.54307/2024.NWMJ.87.
  • 19. Banister T, Spiking J, Ayaru L. Discharge of patients with an acute upper gastrointestinal bleed from the emergency department using an extended Glasgow-Blatchford Score. BMJ Open Gastroenterol. 2018;5(1):e000225. doi:10.1136/bmjgast-2018-000225.
  • 20. Chai-Adisaksopha C, Hillis C, Monreal M, Witt DM, Crowther M. Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding. A meta-analysis. Thromb Haemost. 2015;114(4):819-825. doi: 10.1160/TH15-01-0063.
  • 21. Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll D; Intensive Care Study of Coagulopathy (ISOC) investigators. A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care. 2011;15(2):R108. doi: 10.1186/cc10129.
  • 22. Capuzzo M, Volta C, Tassinati T, et al; Working Group on Health Economics of the European Society of Intensive Care Medicine. Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: a multicentre European cohort study. Crit Care. 2014;18(5):551. doi: 10.1186/s13054-014-0551-8.
  • 23. Gabler NB, Ratcliffe SJ, Wagner J, et al. Mortality among patients admitted to strained intensive care units. Am J Respir Crit Care Med. 2013;188(7):800-806. doi:10.1164/rccm.201304-0622OC.
  • 24. Pamela JB, Joseph H, Matthew K, et al. Warfarin Use and Mortality, Stroke, and Bleeding Outcomes in a Cohort of Elderly Patients with non-Valvular Atrial Fibrillation. J Atr Fibrillation. 2019;12(1):2155. doi:10.4022/jafib.2155.
Year 2024, Volume: 10 Issue: 5, 513 - 521, 04.09.2024
https://doi.org/10.18621/eurj.1524168

Abstract

References

  • 1. Aleksandrov A, Mirkov I, Ninkov M, et al. Effects of warfarin on biological processes other than haemostasis: A review. Food Chem Toxicol. 2018;113:19-32. doi:10.1016/j.fct.2018.01.019.
  • 2. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies. Chest. 2016;149(4):951-959. doi: 10.1378/chest.15-1719.
  • 3. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541-544. doi: 10.1038/nature02254.
  • 4. Ma Z, Wang P, Gao Z, Wang R, Khalighi K. Ensemble of machine learning algorithms using the stacked generalization approach to estimate the warfarin dose. PLoS One. 2018;13(10):e0205872. doi: 10.1371/journal.pone.0205872.
  • 5. Remijn JA, Lucas S, Wildeboer B, van Suijlen JD, Adriaansen HJ. Strongly increased international normalized ratio with recombinant Neoplastin R compared with tissue extract Neoplastin Plus in patients initiating oral anticoagulant therapy: implications for anticoagulation dosage. Clin Chem. 2008;54(11):1929-1931. doi: 10.1373/clinchem.2008.111336.
  • 6. Li S, Liu S, Liu XR, Zhang MM, Li W. Competitive tight-binding inhibition of VKORC1 underlies warfarin dosage variation and antidotal efficacy. Blood Adv. 2020;4(10):2202-2212. doi: 10.1182/bloodadvances.2020001750.
  • 7. Isbister GK, Hackett LP, Whyte IM. Intentional warfarin overdose. Ther Drug Monit. 2003;25(6):715-722. doi: 10.1097/00007691-200312000-00010.
  • 8. Shendre A, Parmar GM, Dillon C, Beasley TM, Limdi NA. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy. 2018;38(6):588-596. doi: 10.1002/phar.2089.
  • 9. Leiss W, Méan M, Limacher A, et al. Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism. J Gen Intern Med. 2015;30(1):17-24. doi:10.1007/s11606-014-2993-8.
  • 10. Atmaca Temrel T, Şahin S, Şan İ. What Is The Success Rate of Patients Using Warfarin In Maintaining Their Target International Normalized Ratio Levels? Ankara Med J. 2019;19(2):366-374. doi:10.17098/amj.577304.
  • 11. Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990.
  • 12. Panch SR, Savani BN, Stroncek DF. Transfusion Support in Patients with Hematologic Disease: New and Novel Transfusion Modalities. Semin Hematol. 2019;56(4):227-228. doi:10.1053/j.seminhematol.2019.11.007.
  • 13. Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. 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(11):970-979. doi: 10.7326/0003-4819-124-11-199606010-00004.
  • 14. Zapata L, Hansten P, Panic J, et al. Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592.
  • 15. Leonard C, Brensinger C, Bilker W, et al. Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics. Int J Cardiol. 2017;228:761-770. doi:10.1016/j.ijcard.2016.11.245.
  • 16. Erdoğan M, Ayhan H, Çolak Ş, et al. Epidemiological features of warfarin overdose and efficacy of prothrombin complex concentrates. J Exp Clin Med. 2014;30(4):327-330. doi:10.5835/jecm.omu.30.04.009.
  • 17. Costa-Lima C, Fiusa MM, Annichino-Bizzacchi JM, de Paula EV. Prothrombin complex concentrates in warfarin anticoagulation reversal. Rev Bras Hematol Hemoter. 2012;34(4):302-304. doi:10.5581/1516-8484.20120076.
  • 18. Güven O, Demireller M. Emergency department admissions and hemorrhage risk in patients on warfarin-containing drugs: a retrospective study. Northwestern Med J. 2024;4(1):41-47. doi:10.54307/2024.NWMJ.87.
  • 19. Banister T, Spiking J, Ayaru L. Discharge of patients with an acute upper gastrointestinal bleed from the emergency department using an extended Glasgow-Blatchford Score. BMJ Open Gastroenterol. 2018;5(1):e000225. doi:10.1136/bmjgast-2018-000225.
  • 20. Chai-Adisaksopha C, Hillis C, Monreal M, Witt DM, Crowther M. Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding. A meta-analysis. Thromb Haemost. 2015;114(4):819-825. doi: 10.1160/TH15-01-0063.
  • 21. Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll D; Intensive Care Study of Coagulopathy (ISOC) investigators. A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care. 2011;15(2):R108. doi: 10.1186/cc10129.
  • 22. Capuzzo M, Volta C, Tassinati T, et al; Working Group on Health Economics of the European Society of Intensive Care Medicine. Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: a multicentre European cohort study. Crit Care. 2014;18(5):551. doi: 10.1186/s13054-014-0551-8.
  • 23. Gabler NB, Ratcliffe SJ, Wagner J, et al. Mortality among patients admitted to strained intensive care units. Am J Respir Crit Care Med. 2013;188(7):800-806. doi:10.1164/rccm.201304-0622OC.
  • 24. Pamela JB, Joseph H, Matthew K, et al. Warfarin Use and Mortality, Stroke, and Bleeding Outcomes in a Cohort of Elderly Patients with non-Valvular Atrial Fibrillation. J Atr Fibrillation. 2019;12(1):2155. doi:10.4022/jafib.2155.
There are 24 citations in total.

Details

Primary Language English
Subjects Emergency Medicine
Journal Section Original Articles
Authors

Osman Sezer Çınaroğlu 0000-0002-3860-2053

Melih Şengül 0009-0007-3268-2359

Deniz Çınaroğlu 0009-0009-4349-9116

Semih Musa Coşkun 0009-0005-6495-1205

Ejder Saylav Bora 0000-0002-2448-2337

Early Pub Date August 27, 2024
Publication Date September 4, 2024
Submission Date July 29, 2024
Acceptance Date August 27, 2024
Published in Issue Year 2024 Volume: 10 Issue: 5

Cite

AMA Çınaroğlu OS, Şengül M, Çınaroğlu D, Coşkun SM, Bora ES. Investigation of warfarin overdose and related factors in the emergency department. Eur Res J. September 2024;10(5):513-521. doi:10.18621/eurj.1524168

e-ISSN: 2149-3189 


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