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Table of Contents
Year : 2014  |  Volume : 17  |  Issue : 2  |  Page : 173-174
Angioedema due to the new oral anticoagulant rivaroxaban

1 Department of Cardiology, Faculty of Medicine, University of Baskent, İzmir, Turkey
2 Department of Neurology, Faculty of Medicine, University of Baskent, İzmir, Turkey
3 Department of Radiology, Faculty of Medicine, University of Baskent, İzmir, Turkey
4 Department of Dermatology, Faculty of Medicine, University of Baskent, İzmir, Turkey

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Date of Web Publication1-Apr-2014

How to cite this article:
Altin C, Ozturkeri OY, Gezmis E, Askin U. Angioedema due to the new oral anticoagulant rivaroxaban. Ann Card Anaesth 2014;17:173-4

How to cite this URL:
Altin C, Ozturkeri OY, Gezmis E, Askin U. Angioedema due to the new oral anticoagulant rivaroxaban. Ann Card Anaesth [serial online] 2014 [cited 2023 Jan 27];17:173-4. Available from:

The Editor,

Angioedema is characterized by localized rapid swelling of the dermis, subcutaneous tissue or mucosa and sub-mucosal tissues of the upper respiratory or gastrointestinal tract. Swellings of the oral-cavity, tongue or larynx can lead to life-threatening airway obstruction and death unless relieved immediately. [1]

Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia occurring in 1-2% of the general population. [2],[3] Major mortality and morbidity in patients with AF are associated with stroke and systemic embolism. The CHA 2 DS 2 -VASc score is a clinical prediction for estimating the risk of stroke in patients with non-valvular AF, used to determine whether anticoagulation therapy is required or not. [3],[4] Although warfarin is the most widely prescribed oral anticoagulant therapy, it has several shortcomings such as interactions with many commonly used medications, foods and requirement of monitoring of its activity by an international normalized ratio (INR). Besides due to its narrow therapeutic index, it is difficult to maintain patients within a defined anticoagulation range (INR 2-3) and unfortunately in the majority of the patients on warfarin therapy the INR is outside the target range. [5] New oral anticoagulants offer more favorable option in some patients with non-valvular AF. We present a case of angioedema after therapy with new oral anticoagulant rivaroxaban.

A 66-year-old female patient presented with numbness of her face in the preceding 2 days. She has been a diagnosed case of coronary artery disease and hypertension and was treated with carvedilol, ramipril, and acetylsalicylic acid for 14 years. On neurological examination, she had hypoesthesia of lips and the upper right side of her cheek. On brain magnetic resonance imaging, multiple, small, acute infarctions in vermis and bilateral cerebellar hemispheres, thought to be embolic infarctions, were seen [Figure 1]. Her electrocardiography revealed sinus rhythm with anterior QS pattern. Echocardiography showed anterior wall motion abnormality with a small apical aneurysm and mild mitral regurgitation. Ejection fraction was 40%. On 24 h Holter monitoring; multiple self-terminating episodes of AF were detected [Figure 2] and the patient was diagnosed with paroxysmal AF. The patient's CHA 2 DS 2 -VASc score was seven points and based on the European Society of Cardiology Committee Guidelines, [4] oral rivaroxaban was initiated as an oral anticoagulation therapy. She did not have a history of allergic reaction to any medication or food. After the fourth dose, severe itching, redness and urticarial lesions were noticed all over her body and simultaneously angioedema on both eyes and lips occurred. She had mild shortness of breath and bronchospasm. After checking the airway, intravenous antihistamine and methylprednisolone 60 mg were administrated. Normal saline and oxygen were also started as supportive therapy. Endotracheal intubation/nasopharyngeal airway or epinephrine were not required. Patient's angioedema and allergic symptoms subsided gradually. Oral rivaroxaban was stopped and patient's allergic symptoms did not recur. However, due to lack of the facility, serum biomarkers of allergic reactions, such as tryptase, histamine, and immunoglobulin E (IgE) levels could not be measured. Patient was diagnosed with angioedema due to the new oral anticoagulant rivaroxaban.
Figure 1: Multiple, small, acute infarctions in vermis and bilateral cerebellar hemispheres on brain magnetic resonance imaging and diffusion-weighted imaging

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Figure 2: Multiple self-terminating atrial fibrillation episodes on 24 h Holter monitoring

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Although warfarin is in use for decades in patients with AF, the significant variability in dose-response, the narrow therapeutic index and the numerous drug and dietary interactions associated with its use have led clinicians to search for alternative agents. Rivaroxaban, a new oral anticoagulant, directly inhibits activated factor X and recommended as an alternative for the prevention of stroke and systemic embolism in patients with non-valvular AF with one or more risk factors such as: Congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack. [6] Rivaroxaban has less adverse interactions than warfarin and monitoring of its activity by standard blood tests is not required.

Lack of long term follow-up is the main handicap of this novel oral anticoagulant. [6] There are still some unresolved issues about its clinical usage in renal impairment, liver diseases, pregnancy and lactating mothers. There is no validated monitoring technique and antidote for reversing bleeding with rivaroxaban. Drug interactions are not well-known. There is also lack of data about switching from warfarin to rivoraxaban and vice versa. [6] The most common adverse reactions with rivoraxaban are bleeding complications, including major bleeding events. Fainting, itching, and muscle spasms were also reported. [6] Angioedema and anaphylaxis are serious side-effects that can limit this novel anticoagulants' clinical use. Drug-induced angioedema has been reported to occur in response to a wide range of drugs. [7] There are different underlying mechanisms; including allergic and non-allergic reactions in drug-induced angioedema. [7] In our patient, the combination of urticaria and angioedema is typical for IgE-mediated allergic reactions and histamine acts as the main biogenic mediator in allergic angioedema. In the present patient, rivaroxaban may have elicited this IgE-mediated allergic angioedema.

   References Top

1.Jaiganesh T, Wiese M, Hollingsworth J, Hughan C, Kamara M, Wood P, et al. Acute angioedema: Recognition and management in the emergency department. Eur J Emerg Med 2013;20:10-7.  Back to cited text no. 1
2.Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: The Framingham Heart Study. Circulation 2004;110:1042-6.  Back to cited text no. 2
3.Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719-47.  Back to cited text no. 3
4.Lip GY, Frison L, Halperin JL, Lane DA. Identifying patients at high risk for stroke despite anticoagulation: A comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke 2010;41:2731-8.  Back to cited text no. 4
5.Boulanger L, Kim J, Friedman M, Hauch O, Foster T, Menzin J. Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice. Int J Clin Pract 2006;60:258-64.  Back to cited text no. 5
6.Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91.  Back to cited text no. 6
7.Inomata N. Recent advances in drug-induced angioedema. Allergol Int 2012;61:545-57.  Back to cited text no. 7

Correspondence Address:
Cihan Altin
Department of Cardiology, University of Baskent, Faculty of Medicine, 6471/5 Sokak, No.: 7, Yalİ Mahallesi, Bostanlı, Karşıyaka/ızmir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9784.129888

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