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CASE REPORT
Year : 2019  |  Volume : 29  |  Issue : 4  |  Page : 180-182

An uncommon case of spontaneous hemopericardium in a patient treated with rivaroxaban


1 Department of Clinical and Experimental Medicine, Section of Cardiology, Policlinico San Marco, Corso Europa, Zingonia BG, Messina, Italy
2 Department of Clinical and Experimental Medicine - Section of Cardiology, University of Messina, Policlinico G. Martino, Messina, Italy

Date of Web Publication27-Jan-2020

Correspondence Address:
Luca Longobardo
Department of Clinical and Experimental Medicine - Section of Cardiology, University of Messina, Policlinico G. Martino, Via Consolare, Valeria No. 12, 98100, Messina
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcecho.jcecho_57_19

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  Abstract 


We describe a case of an 88-year-old woman with a severe bluntly ematic pericardial effusion. Radiological and laboratory examinations excluded all the most common causes of hemopericardium, and the diagnosis of spontaneous hemopericardium associated with the treatment with rivaroxaban was made. This is the first case report describing a hemopericardium in a patient treated with rivaroxaban who did not take other herbal products or drugs that may significantly increase rivaroxaban blood levels. This report emphasizes the need for the careful use of new oral anticoagulants, and the importance of taking in mind uncommon side effects. Spontaneous hemopericardium should be considered in these patients.

Keywords: Echocardiography, hemopericardium, new oral anticoagulant, pericardial effusion, rivaroxaban


How to cite this article:
Ioppolo AM, Longobardo L, D'Isa S, De Gregorio P, Manfredi M, De Cesare NB. An uncommon case of spontaneous hemopericardium in a patient treated with rivaroxaban. J Cardiovasc Echography 2019;29:180-2

How to cite this URL:
Ioppolo AM, Longobardo L, D'Isa S, De Gregorio P, Manfredi M, De Cesare NB. An uncommon case of spontaneous hemopericardium in a patient treated with rivaroxaban. J Cardiovasc Echography [serial online] 2019 [cited 2020 Aug 11];29:180-2. Available from: http://www.jcecho.org/text.asp?2019/29/4/180/276900




  Introduction Top


New oral anticoagulants (NOACs) have been approved for the prophylaxis and treatment of arterial and venous thromboembolism. Although they showed to have similar or superior safety compared with Vitamin K antagonists (VKAs), bleedings are not uncommon in patients treated by NOACs and life-threatening events have been reported. The most common sites of bleeding include gastrointestinal, genitourinary, and intracranial ones. Hemopericardium is a rare eventuality in patients treated with NOACs. Herein, we describe the first case report, to our knowledge, of a slowly accumulating spontaneous hemopericardium in a patient treated with rivaroxaban who did not take any other herbal products or drugs that may increase rivaroxaban blood levels.


  Case Report Top


A 88-year-old Caucasian woman was admitted to the emergency room complaining of orthopnea and weakness with gradual onset. Her medical history included dyslipidemia, obesity, and permanent pacemaker implantation for sick sinus syndrome in 2003. Her routine drug therapy consisted of esomeprazole and rosuvastatin. Six months before the onset of the symptoms, full dosage rivaroxaban (20 mg once daily) was prescribed for permanent atrial fibrillation, according to her estimated glomerular filtration rate (63 ml/min). The patient denied fever, weight loss, and any history of trauma in the previous weeks. The heart rate was 70 beats/min, blood pressure was 130/70 mmHg, and oxygen saturation on room air was 98%. The physical examination revealed jugular vein congestion, faint heart sound, no murmurs, and leg swelling. Electrocardiogram showed atrial fibrillation with ventricular pacing. The laboratory tests did not reveal significant alterations, including leukocytosis or anemia or hypothyroidism. A chest radiograph showed a significant cardiomegaly without pleural effusion and a transthoracic echocardiogram (TTE) found a 36-mm circumferential pericardial effusion without the signs of tamponade [Figure 1] and [Figure 2] and Video 1]. The patient was transferred to the intensive care unit and he underwent pericardiocentesis to provide a relief of symptoms. Rivaroxaban was discontinued before the drainage. The pericardiocentesis removed 850 ml of a bluntly ematic effusion without clot. Two days later, 450 ml of blood more were drained. Cultures of the pericardial effusion for bacteria (aerobic and anaerobic), and fungi were performed and resulted to be negative. Moreover, Mantoux-Tine test for the research of Mycobacterium tuberculosis was negative too. To rule out viral etiology a complete virology screening (Parvovirus B19, adenovirus, echo-virus, Epstein–Barr virus, rubella virus, Citomegalovirus, and Coxakievirus) was performed, but it was negative as well as antibodies for autoimmune diseases. The cytological analysis did not find malignant cells, and a total body computed tomography scan ruled out the presence of cancer masses.
Figure 1: Transthoracic echocardiography four-chamber view showing a severe circumferential pericardial effusion (maximum diameter 30 mm)

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Figure 2: Transthoracic echocardiography off-axis parasternal short axis view showing the same pericardial effusion

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Serial TTEs were performed, and showed that pericardial effusion was stable after the drainage. The patient was discharged from the hospital in stable conditions without anticoagulation therapy. An ETT performed 1 month after discharge did not show pericardial effusion anymore.


  Discussion Top


NOACs are as effective as VKAs in preventing stroke and systemic embolism and lowering the risk of major bleeding and rivaroxaban, an orally bioavailable FXa inhibitor, is one of the most used.[1] Although the use of rivaroxaban reduced the rate of bleedings, it has been found that more than 5% of bleedings reported in patients treated with NOACs occur in patients treated with rivaroxaban, with an incidence of fatal bleeds up to 0.4%.[2]

Spontaneous hemopericardium in patients receiving NOACs is a rare condition, reported in patients treated with dabigatran[3],[4] apixaban[5],[6],[7] and rivaroxaban.[8],[9],[10],[11],[12] However, to the best of our knowledge, within reports of a spontaneous hemopericardium in patients treated with rivaroxaban, this is the first one in whom no other herbal products or drugs that may increase rivaroxaban blood levels by inhibiting P-glycoprotein and cytochrome P450 3A4 (CYP3A4) activity, or that increase the hemorrhagic risk, were taken. In detail, Shivamurthy et al.[8] reported that in their patient, the bleeding was probably caused by the contemporary intake of saw palmetto, an herbal product that could have to increase rivaroxaban activity. Similarly, Menendez and Michel,[9] Boone[10] and Oladiran et al.[11] reported that their patients took several other medications known to be metabolized through CYP3A4, underlining the risk that most physicians are familiar with recommendations to monitor renal function in patients prescribed rivaroxaban, but often fail to evaluate possible interactions with other agents having CYP3A4 inhibitory or inducer activity. Finally, Xu and MacIsaac[12] stated that their patient was treated with high doses of aspirin, ticagrelor, and ibuprofen.

The evidence that a potential life-threatening condition like a spontaneous hemopericardium could onset even when all the proper cautions in terms of renal function and drug interactions have been taken, raises some concerns about the lack of commercially available coagulation assays for the evaluation of anticoagulant levels in patients using NOACs and about the lack of antidotes. A new antidote for factor Xa inhibitors, Andexanet Alfa, has been recently tested in patients treated with Apixaban or rivaroxaban and it showed to markedly reduce anti-factor Xa activity and to have an excellent or good hemostatic efficacy at 12 h in 82% of patients.[13] However, this drug is not yet available in many countries.


  Conclusion Top


In a scenario in which the number of patients receiving NOACs will increase in the next years, the evidence of uncommon, but dangerous complications are particularly important and reporting all possible adverse events associated with NOACs becomes essential. Clinicians should consider the possibility of hemopericardium in patients treated with NOACs who report dyspnea and have pericardial effusion on echocardiography, even when all the proper cautions in terms of renal function and drug interactions have been taken.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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. 1
    
2.
Dentali F, Riva N, Crowther M, Turpie AG, Lip GY, Ageno W. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: A systematic review and meta-analysis of the literature. Circulation 2012;126:2381-91.  Back to cited text no. 2
    
3.
Jelani QU, Gordon R, Schussheim A. Dabigatran-induced spontaneous hemopericardium and cardiac tamponade. Tex Heart Inst J 2017;44:370-2.  Back to cited text no. 3
    
4.
Barton CA, McMillian WD, Sadi Raza S. Hemopericardium in a patient treated with Dabigatran etexilate. Pharmacotherapy 2012;32:e103-7.  Back to cited text no. 4
    
5.
Asad ZUA, Ijaz SH, Chaudhary AMD, Khan SU, Pakala A. Hemorrhagic cardiac tamponade associated with Apixaban: A case report and systematic review of literature. Cardiovasc Revasc Med 2019. pii: S1553-8389 (19) 30228-3.  Back to cited text no. 5
    
6.
Sigawy C, Apter S, Vine J, Grossman E. Spontaneous Hemopericardium in a patient receiving apixaban therapy:First case report. Pharmacotherapy 2015;35:e115-7.  Back to cited text no. 6
    
7.
Cinelli M, Uddin A, Duka I, Soomro A, Tamburrino F, Ghavami F, et al. Spontaneous hemorrhagic pericardial and pleural effusion in a patient receiving apixaban. Cardiol Res 2019;10:249-52.  Back to cited text no. 7
    
8.
Shivamurthy P, Brar N, Therrien ML. Isolated hemopericardium associated with rivaroxaban:First case report. Pharmacotherapy 2014;34:e169-72.  Back to cited text no. 8
    
9.
Menendez D, Michel J. Hemopericardium with tamponade following rivaroxaban administration and its attenuation by CYP3A4 inhibitors. Proc (Bayl Univ Med Cent) 2016;29:414-5.  Back to cited text no. 9
    
10.
Boone S. Cardiac tamponade associated with rivaroxaban. Del Med J 2015;87:206-7.  Back to cited text no. 10
    
11.
Oladiran O, Segal J, Nwosu I, Nazir S. A rare case of spontaneous cardiac tamponade induced by concomitant use of rivaroxaban and amiodarone. Case Rep Cardiol 2018;2018:1650716.  Back to cited text no. 11
    
12.
Xu B, MacIsaac A. Life-threatening haemorrhagic pericarditis associated with rivaroxaban. Int J Cardiol 2014;174:e75-6.  Back to cited text no. 12
    
13.
Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al. Full study report of Andexanet alfa for bleeding associated with factor xa Inhibitors. N Engl J Med 2019;380:1326-35.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2]


This article has been cited by
1 Rivaroxaban
Reactions Weekly. 2020; 1793(1): 396
[Pubmed] | [DOI]



 

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