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Year : 2023  |  Volume : 28  |  Issue : 2  |  Page : 167-172

Analysis of burden and outcomes of anticoagulant induced adverse drug effects at a tertiary care centre

Department of Medicine Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai, Maharashtra, India

Date of Submission24-Nov-2022
Date of Decision16-Dec-2022
Date of Acceptance16-Feb-2023
Date of Web Publication21-Mar-2023

Correspondence Address:
Alhad A Mulkalwar
Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Parel, Mumbai 400012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmh.IJMH_76_22

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Background: Anticoagulants are among the most commonly used drugs in hospitalized patients known to cause adverse drug reactions (ADRs). They have commonly been used as standard therapy in venous thromboembolism, stroke prevention, etc. Objectives: The authors aimed to assess the incidence of ADRs, clinical profile, severity and causality among the admitted patients taking anticoagulants in a tertiary care hospital. Materials and Methods: This was a hospital-based, prospective, observational, non-interventional cohort study undertaken in the General Medicine Wards of King Edward Memorial Hospital, Mumbai from June 2017 to December 2018. Every patient’s data was recorded using a structured ADR reporting form. The baseline parameters, medical history and underlying diseases, clinical data, characteristics of ADRs, and details of medication responsible for ADRs, as well as details of the drugs used for treatment of ADRs were recorded. The data was analyzed using descriptive statistics with the Statistical Packages for the Social Sciences (SPSS) version 26.0 software. Results: Out of the 164 patients admitted due to ADRs within the study period, 32 (19.5%) had developed ADRs due to anticoagulant treatment. Most anticoagulant-related ADRs involved the vascular system (n = 32). The severity of ADR was found to be mild in one patient (3.1%), moderate in 22 patients (68.8%), and severe in nine patients (28.1%). Twenty (62.5%) patients completely recovered, nine (28.1%) patients were still recovering (at the time of the analysis of the data), and three (9.4%) patients had a fatal outcome. Presence of systemic comorbidities and polypharmacy were found to be significant risk factors associated with anticoagulant-associated ADRs. Conclusion: Anticoagulants commonly cause ADRs in the study population. Patient education at the time of prescription can prevent many ADRs due to medication error or poor compliance. In addition, installing a better surveillance system in hospitals could alleviate the prevalence of ADRs.

Keywords: Adverse effects, vascular system, warfarin

How to cite this article:
Tongaonkar AH, Joshi KS, Mulkalwar AA, Gajare SD. Analysis of burden and outcomes of anticoagulant induced adverse drug effects at a tertiary care centre. Int J Med Health Dev 2023;28:167-72

How to cite this URL:
Tongaonkar AH, Joshi KS, Mulkalwar AA, Gajare SD. Analysis of burden and outcomes of anticoagulant induced adverse drug effects at a tertiary care centre. Int J Med Health Dev [serial online] 2023 [cited 2023 May 28];28:167-72. Available from: https://www.ijmhdev.com/text.asp?2023/28/2/167/372161

  Introduction Top

Adverse drug reactions (ADRs) could be defined as “appreciably harmful or unpleasant reactions resulting from interventions related to the use of medicinal products.”[1] ADRs are considered as one of the leading causes of hospital admissions and a substantial burden on healthcare systems.[2] Estimated 20% ADRs lead to hospitalization and up to 10% hospital admissions in developing countries are due to ADRs, of which almost two-third are preventable.[3] ADRs are more common among the elderly.[4] Adverse drug events can range from mild to life-threatening reactions resulting in serious morbidities or mortality as well as financial burden to the patient.

Anticoagulants antagonize the coagulation process. These are one of the most commonly used drugs in out-patient departments as well as hospitalized patients.[5] Anticoagulants like aspirin and oral vitamin K antagonists like warfarin are widely used to prevent thromboembolic events in atrial fibrillation and stroke patients. Anticoagulants account for estimated 8.77–15.1% of ADRs in hospitalized patients.[6] Of these, vascular and cutaneous systems are most commonly affected due anticoagulant-induced toxicity. Hemorrhage is the most frequent ADR following the use of oral anticoagulants, with the most common site of bleeding being the gastrointestinal tract. However, the anticoagulant-associated ADR that is associated with highest mortality is intracranial bleed (up to 50%).[7] Blood clots (therapeutic failure), cognitive distortion, headache and hair loss are some of the other adverse effects linked to anticoagulants.[8] As most of these ADRs are probable and preventable, adequate patient counseling can facilitate early diagnosis and treatment. Pharmacovigilance of anticoagulant drugs can accelerate the early identification of ADRs and provide valuable feedback to physicians. This study is aimed at assessing the incidence of ADRs among the admitted patients in a tertiary care hospital taking anticoagulants. It also assessed the clinical profile of patients with anticoagulant-associated ADRs, along with the severity, causality, and preventability of these ADRs.

  Materials and Methods Top

This was a hospital-based, observational, prospective, non-interventional cohort study undertaken at Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai. A structured ADR reporting form was used to record the patient’ data. It was conducted in the General Medicine Wards. The study spanned in the Department of Medicine from June 2017 till December 2018. It was initiated after obtaining approval from the Departmental Review Board and the Institutional Ethics Committee (IEC/167/2017). The study included all consenting patients, aged >21 years, who either developed anticoagulant-induced ADR while admitted for another medical condition or were admitted to the medical wards for ADRs following the use of anticoagulants. The study excluded patients non-compliant to the prescribed medications, those with intentional or accidental poisoning and drug abuse.

The relevant data with respect to demographic details, clinical condition and comorbidities, laboratory parameters, medications, etc was obtained after assessing the baseline parameters. The medical history and underlying diseases, clinical data, characteristics of ADRs, and details of medication responsible for ADRs (suspected drug, dosage, route of administration, indication, date of commencement and stoppage of therapy, and concomitant drugs) as well as medication for treatment of ADRs were obtained from the clinical notes, medication charts, clinical examination, interviews with patient or his/her relatives or caregivers or ward staff, the treatment sheets, drug administration charts, dispensing records, and pill/injection count validation. All patients were followed up till death or till discharge from the hospital. The ADRs were recorded in detail in a descriptive format. The class of drugs causing the ADRs, systems affected, as well as the onset, duration, and progress of the drugs causing ADRs was recorded along with the severity and seriousness of the reactions and the treatment given for the same. Detailed information pertaining to the adverse event was collected - the likely causative drug/class of drug, causality (WHO-UMC scale),[9] severity (Hartwig and Siegel scale),[10] avoidability (Halla’s criteria),[11] and outcome. The data were analyzed using descriptive statistics with the SPSS version 26.0 software.

  Results Top

Out of the 164 patients admitted due to ADRs within the study period, 32 (19.5%) developed ADRs due to anticoagulants (15 males and 17 females). However, there was no statistically significant correlation found between the age and gender of the patient with the severity of the ADR or outcome of the treatment. The age and gender distribution of the subjects is given in [Table 1].
Table 1: Age and gender distribution of patients

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All cases of anticoagulant-induced ADR were caused by warfarin. The severity of ADR was found to be mild in one patient (3.1%), moderate in 22 patients (68.8%), and severe in nine patients (28.1%). The causality of one subject was found to be certain, and that of the remaining 31 subjects was found to be probable (WHO-UMC scale).[9] The mean duration of stay was 6.03 days, with a standard deviation of 5.190.[12] The summary of the outcome in patients is given in [Table 2].
Table 2: Outcome of patients of the study

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All ADRs due to anticoagulants were possibly avoidable (n = 32) as per the Halla’s criteria.[11] All the anticoagulant (warfarin) induced ADRs involved the vascular system (n = 32) as shown in [Table 3]. Of these, two patients had warfarin-induced intracranial bleeding and one patient had warfarin-induced subdural hemorrhage—all three patients succumbed to the illness. Nine patients were asymptomatic with deranged INR (international normalized ratio), one patient was incidentally diagnosed of warfarin toxicity and remaining patients with warfarin toxicity (n = 19) presented with ecchymotic patches, hematuria, hematemesis, epistaxis, subconjunctival hemorrhage, etc. 15 (46.88%) out of the 32 patients with ADRs had comorbidities, and 10 patients (31.25%) were on polypharmacy. However, there was no statistically significant correlation found between any of the comorbidities with the severity of the ADR or outcome of the treatment.
Table 3: Information of the patients suffering from anticoagulant-induced ADRs

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  Discussion Top

Anticoagulants are widely used all over the world in outpatients and hospitalized patients, especially in those with existing comorbidities. However, these are also known to cause ADRs frequently in patients on concomitant medications, which may result in poor compliance.[13] This might exacerbate the existing disease/comorbidity or prolong the treatment, resulting in complications, sequelae, or death. Polypharmacy (higher drug count) and higher comorbidity scores have been consistently reported as risk factors for ADRs, especially amongst geriatric patients.[14] The present study is consistent with the findings with the two major risk factors being polypharmacy (n = 15) and presence of significant comorbidities (n = 13). The overall prevalence of ADRs with anticoagulant drugs in hospitalized patients is estimated to vary from 8.77% to 15.1%.[6] These findings were consistent with the present study that had an ADR prevalence of 19.5%, with all of them affecting the vascular system. Physicians should also be educated on drugs that will likely interact with anticoagulants and prescribe with caution or not prescribe at all. To help the patient to cope with the unpleasant ADRs and facilitate early reporting, physicians should educate patients about the possible ADRs before commencing treatment. This will also improve patient compliance. Patients should also be encouraged for follow-up assessments that may help detect the milder symptoms, such as petechial rash, bruising, and bleeding gums, before the ADR intensifies.[15]


The study evaluated patients admitted only to the General Medicine wards. Selecting all the patients from a single hospital might affect the external validity of the study. Lastly, the assessment of whether the ADR was responsible for the increase in the duration of hospital stay of the patient or whether the death was caused due to the ADR or the underlying disease, was not performed as it was difficult to establish the same.

  Conclusion Top

This study demonstrates the various anticoagulant-induced ADRs and further emphasizes the importance of early reporting, diagnosis, and treatment of these ADRs. This requires patient education and a better surveillance system in place. The physicians should also be educated on proper use of anticoagulants as well as knowledge of drugs that interact with anticoagulants.


The authors have no acknowledgements to report.

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Conflicts of interest

The authors have no conflicts of interest to report.

  References Top

Coleman JJ, Pontefract SK Adverse drug reactions. Clin Med (Lond) 2016;16:481-5.  Back to cited text no. 1
Giardina C, Cutroneo PM, Mocciaro E, Russo GT, Mandraffino G, Basile G, et al. Adverse drug reactions in hospitalized patients: Results of the FORWARD (Facilitation of Reporting in Hospital Ward) Study. Front Pharmacol 2018;9:350.  Back to cited text no. 2
Angamo MT, Chalmers L, Curtain CM, Bereznicki LR Adverse-drug-reaction-related hospitalisations in developed and developing countries: A review of prevalence and contributing factors. Drug Saf 2016;39:847-57.  Back to cited text no. 3
Lavan AH, Gallagher P Predicting risk of adverse drug reactions in older adults. Ther Adv Drug Saf 2016;7:11-22.  Back to cited text no. 4
Alquwaizani M, Buckley L, Adams C, Fanikos JA A review of the pharmacology, dosing, and complications. Curr Emerg Hosp Med Rep 2013;1:83-97.  Back to cited text no. 5
Piazza G, Nguyen TN, Cios D, Labreche M, Hohlfelder B, Fanikos J, et al. Anticoagulation-associated adverse drug events. Am J Med 2011;124:1136-42.  Back to cited text no. 6
Amaraneni A, Chippa V, Rettew AC Anticoagulation safety [updated 2022 Nov 27]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022.  Back to cited text no. 7
Watras MM, Patel JP, Arya R Traditional anticoagulants and hair loss: A role for direct oral anticoagulants? A review of the literature. Drugs Real World Outcomes 2016;3:1-6.  Back to cited text no. 8
Lindquist M, Edwards IR The WHO Programme for international drug monitoring, its database, and the technical support of the Uppsala monitoring center. J Rheumatol 2001;28:1180-7.  Back to cited text no. 9
Hartwig SC, Siegel J, Schneider PS Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 10
Hallas J, Harvald B, Gram LF, Grodum E, Brøsen K, Haghfelt T, et al. Drug related hospital admissions: The role of definitions and intensity of data collection, and the possibility of prevention. J Intern Med 1990;228:83-90.  Back to cited text no. 11
Geer MI, Koul PA, Tanki SA, Shah MY Frequency, types, severity, preventability and costs of adverse drug reactions at a tertiary care hospital. J Pharmacol Toxicol Methods 2016;81:323-34.  Back to cited text no. 12
Schurig AM, Böhme M, Just KS, Scholl C, Dormann H, Plank-Kiegele B, et al. Adverse drug reactions (ADR) and emergencies. Dtsch Arztebl Int 2018;115:251-8.  Back to cited text no. 13
Pérez Menéndez-Conde C, Bermejo Vicedo T, Delgado Silveira E, Carretero Accame E Adverse drug reactions which provoke hospital admission. Farm Hosp 2011;35:236-43.  Back to cited text no. 14
Sennesael AL, Larock AS, Devalet B, Verschuren F, Muschart H, et al. Preventability of serious thromboembolic and bleeding events related to the use of oral anticoagulants: A prospective study. Br J Clin Pharmacol 2018;84: 1544-1556.  Back to cited text no. 15


  [Table 1], [Table 2], [Table 3]


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