Frequency of bleeding complications in Algerian patients treated with the vitamin K antagonist acenocoumarol and associated factors


  • Malika Belkacemi Faculty of Medicine, University DjellaliLiabes, SidiBel Abbes, Algeria
  • Yassine Merad Faculty of Medicine, University DjellaliLiabes, SidiBel Abbes, Algeria
  • Abdellah Berber Faculty of Medicine, University DjellaliLiabes, SidiBel Abbes, Algeria



Vitamin K antagonist, Acenocoumarol, Bleeding, Oral anticoagulant


Background: The major complication of vitamin K antagonist (VKA) therapy is bleeding. This study aimed to estimate the rate of hemorrhagic accidents and identify the hemorrhagic factors in Algerian patients treated by the VKA, acenocoumarol.

Methods: We performed a cross-sectional study in patients undergoing VKA therapy, followed in the cardiology department of the University Hospital of Sidi Bel Abbes.

Results: One hundred patients were included. We recorded 22 cases of bleeding. Overdose and concomitant use of drugs that interfere with the acenocoumarol effect are significant risk factors of bleeding.

Conclusions: Knowledge of predictive factors for VKA-related excessive anticoagulation seems to be of the utmost importance for improving patient management. There is a need for a national registry to assess the efficacy and safety of drug use in the short and long term. This pilot study is a cornerstone in the development of oral anticoagulation therapy monitoring in our region.


Handin RI.The History of Antithrombotic Therapy: The Discovery of Heparin, the Vitamin K Antagonists, and the Utility of Aspirin. Hematol Oncol Clin North Am. 2016;30(5):987-93.

Tie JK, Stafford DW. Structural and functional insights into enzymes of the vitamin K cycle. J Thromb Haemost. 2016;14(2):236-47.

Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-67.

Levi M. Epidemiology and management of bleeding in patients using vitamin K antagonists. J Thromb Haemost. 2009;7(1):103-6.

Ufer M. Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46.

Chetoui AS, Ztati M Khatouri A. Bleeding the avk study witness cases: about 200 patients. Int J of Adv Res. 2016;4(10):81-5.

Mbarka FB, Jeddou KB, Allouche E, Boukhris I, Khalfallah N, Baccar H. Bleeding and asymptomatic overdose in patients under Vitamin K antagonist therapy: Frequency and risk factors. Egypt Heart J. 2018;70(1):45-9.

Tremey B. Epidémiologie des accidents hémorragiques survenant chez les patients sous antivitamine K. JEUR. 2009;22(1001):S1-10

Gomes T, Mamdani MM, Holbrook AM, Paterson JM, Hellings C, Juurlink DN. Rates of hemorrhage during warfarin therapy for atrial fibrillation. Cmaj. 2013;185(2):E121-7.

Sjögren V, Grzymala-Lubanski B, Renlund H, Friberg L, Lip GY, Svensson PJ et al. Safety and efficacy of well managed warfarin. A report from the Swedish quality register Auricula. Thromb Haemost. 2015;113(6):1370-7.

Palareti G, Antonucci E, Migliaccio L, Erba N, Marongiu F, Pengo V et al. Vitamin K antagonist therapy: changes in the treated populations and in management results in Italian anticoagulation clinics compared with those recorded 20 years ago. Intern Emerg Med. 2017;12(8):1109-19.

van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med. 1993;153(13):1557-62.

Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348(9025):423-8.

Fang MC, Chang Y, Hylek EM, Rosand J, Greenberg SM, Go AS et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141(10):745-52.

Torn M, Bollen WL, van der Meer FJ, van der Wall EE, Rosendaal F. R.Risks of oral anticoagulant therapy with increasing age. Arch Intern Med. 2005;165(13):1527-32.

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):970-9.

Ben Ameur Y, Chaabane O, Zairi I, Longo S, Battikh K, Slimane ML. Acute hemorrhage due anti-vitamin K agents. A prognostic and descriptive study. Tunis Med. 2009;87(11):763-9.

Copland M, Walker ID, Tait RC. Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation. Arch Intern Med. 2001;161(17):2125-8.

Hylek EM. Complications of oral anticoagulant therapy: bleeding and nonbleeding, rates and risk factors. Semin Vasc Med. 2003;3(3):271-8.

Tang EO, Lai CS, Lee KK, Wong RS, Cheng G, Chan TY.Relationship between patients' warfarin knowledge and anticoagulation control. Ann Pharmacother. 2003;37(1):34-9.

Palareti G, Legnani C, Guazzaloca G, Lelia V, Cosmi B, Lunghi B et al.Risks factors for highly unstable response to oral anticoagulation: a case-control study. Br J Haematol. 2005;129(1):72-8.

Barcellona D, Contu P, Marongiu F. Patient education and oral anticoagulant therapy. Haematologica. 2002;87(10):1081-6.

Mzoughi K, Zairi I, BenGhorbel F, Ben Kilani M, Kamoun S, Ben Moussa F et al. Evaluation of patients' knowledge on their vitamin K antagonist treatment. Tunis Med. 2018;96(3):182-6.

Casais P, Luceros SA, Meschengieser S, Fondevila C, Santarelli MT, Lazzari MA.Bleeding risk factors in chronic oral anticoagulation with acenocoumarol. Am J Hematol. 2000;63(4):192-6.

da Costa MAC, Krum LK, Geraldino JD, Schafranski MD, Gomes RZ, Reis ES.. Anticoagulation Quality and Complications of using Vitamin K Antagonists in the Cardiac Surgery Outpatient Clinic. Braz J Cardiovasc Surg. 2016;31(3):239-45.

.Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115(21):2689-96.

Dia K, Sarr SA, Mboup MC, Ba DM, Fall PD. Overdose in Vitamin K antagonists administration in Dakar: epidemiological, clinical and evolutionary aspects. Pan Afr Med J. 2016;24:186.

Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med. 1993;95(3):315-28.

Abdelhafiz AH, Wheeldon NM. Results of an open-label, prospective study of anticoagulant therapy for atrial fibrillation in an outpatient anticoagulation. Clin Ther. 2004;26(9):1470-8.

Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, White RH. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group. Ann Intern Med. 1993;118(7):511-20.

DiMarco JP, Flaker G, Waldo AL, Corley SD, Greene HL, Safford RE et al. Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J. 2005;149(4):650-6.

Sam C, Massaro JM, D'Agostino RB Sr, Levy D, Lambert JW, Wolf PA et al. Warfarin and aspirin use and the predictors of major bleeding complications in atrial fibrillation (the Framingham Heart Study). Am J Cardiol. 2004;94(7):947-51.

Hughes M, Lip GY. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. Qjm. 2007;100(10):599-607.

Sachs JJ, Henderson RR. Use of bishydroxycoumarin (dicumarol) in the presence of impaired renal function. J Am Med Assoc. 1952;148(10):839-41.

Shah M, Tsadok AM, Jackevicius CA, Essebag V. Eisenberg, MJ, Rahme E et al.Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014;129(11):1196-203.

Bonde AN, Lip GY, Kamper AL, Fosbøl EL, Staerk L, Carlson N et al. Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation: An Observational Cohort Study. Stroke. 2016;47(11):2707-13.

Pengo V, Legnani C, Noventa F, Palareti G. Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study. Thromb Haemost. 2001;85(3):418-22.

Zenati N, Gaboreau Y, Provencher CB, Albaladejo P, Bosson JL, Pernod G. Anaemia as an independent key risk factor for major haemorrhage in patients treated with vitamin K antagonists: Results of the SCORE prospective cohort. Thromb Res. 2017;151:83-8.

Kuperman A, López-Reyes R, Bosco LJ, Lorenzo A, José B, Farge Bancel D et al. Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism. J Thromb Thrombolysis. 2018;45(3):360-8.

Visser LE, Penning-van Bees FJ, Kasbergen AA, De Smet PA, Vulto AG, Hofman A et al. Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants. Thromb Haemost. 2002;88(5):705-10.

Arboix M, Frati ME, Laporte JR. The potentiation of acenocoumarol anticoagulant effect by amiodarone. Br J Clin Pharmacol. 1984;18(3):355-60.

Fareed J, Thethi I, Hoppensteadt D. Old versus new oral anticoagulants: focus on pharmacology. Annu Rev Pharmacol Toxicol. 2012;52:79-99.

Loffredo L, Perri L, Del Ben M, Angelico F, Violi F. New oral anticoagulants for the treatment of acute venous thromboembolism: are they safer than vitamin K antagonists? A meta-analysis of the interventional trials. Intern Emerg Med. 2015;10(4):499-506.

Palareti G. Direct oral anticoagulants and bleeding risk (in comparison to vitamin K antagonists and heparins), and the treatment of bleeding. Semin Hematol. 2014;51(2):102-11.

Kirchmayer U, Narduzzi S, Mayer F, Tuccori M, Leoni O, Belleudi V et al. Safety and effectiveness of direct oral anticoagulants versus vitamin K antagonists: results from 3 Italian regions. Recenti Prog Med. 2019;110(4):195-202.

Sánchez AM, Martínez BV, Ortiz RM, Fillat CÁ, Rabadán RI, García MJ et al. Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study. Rev Esp Cardiol (Engl Ed). 2020;73(1):14-20.




How to Cite

Belkacemi, M., Merad, Y., & Berber, A. (2021). Frequency of bleeding complications in Algerian patients treated with the vitamin K antagonist acenocoumarol and associated factors. International Journal of Basic & Clinical Pharmacology, 10(11), 1234–1239.



Original Research Articles