Pulmonary embolism four days after interruption of therapy with rivaroxaban

Summary

Thrombosis after cessation of anticoagulation, also named rebound thrombosis, is a matter of concern and controversy. There are only few published data about occurrence of rebound thrombosis associated with non-vitamin K-antagonist oral anticoagulant drugs (NOACs). We report on a 58-year-old male with paroxysmal atrial fibrillation (AF) with a CHA₂DS₂VASC score of 4 who developed central pulmonary embolism four days after interruption of rivaroxaban because of parotid surgery. He had received 40 mg enoxaparin/d. The parotid gland was partially resected within 6 hours without blood loss. Pulmonary embolism and AF occurred on the first postoperative day. He recovered with low-molecular-weight heparin in therapeutic dosages and amiodarone and was discharged with phenprocoumon.

The relevance of a rivaroxaban rebound phenomenon, manifesting as arterial embolism, stroke or venous thromboembolism should be clarified. It should be assessed if rebound-phenomena also exist for the NOACs dabigatran, apixaban and edoxaban. Thus, the randomized trials and registries investigating patients with AF or venous thromboembolism should be re-analysed and, based on these data, recommendations should be developed for situations in which NOAC-therapy has to be interrupted or ceased.

Zusammenfassung

Ob es nach Beendigung einer Antikoagulationstherapie zu einer neuerlichen Thromboembolie, auch „Rebound” genannt, kommen kann, ist umstritten und es gibt nur wenige Daten über dieses Phänomen nach einer Therapie mit nicht Vitamin K-Antagonisten oralen Antikoagulantien (NOAKs). Ein 58-jähriger Mann mit paroxysmalem Vorhofflimmern (AF) und einem CHA₂DS₂VASC Score von 4 erlitt eine zentrale Pulmonalarterienembolie vier Tage nach Unterbrechung der Therapie mit Rivaroxaban wegen eines chirurgischen Eingriffs an der Parotis. Zum Zeitpunkt des Ereignisses stand er unter einer Therapie mit 40 mg Enoxaparin/Tag. Die Parotis wurde in einer 6-stündigen Operation ohne relevanten Blutverlust partiell reseziert. Am ersten postoperativen Tag traten eine Pulmonalembolie und tachykardes AF auf. Er erholte sich unter einer Therapie mit niedermolekularem Heparin in therapeutischer Dosis und Amiodaron und wurde mit einer Therapie mit Phenprocoumon entlassen.

Die Relevanz eines “Rivaroxaban-Rebound-Phänomens”, das als arterielle Embolie, Schlaganfall oder venöse Thromboembolie auftreten kann, sollte genauer erforscht werden. Es sollte festgestellt werden, ob ähnliche Phänomene auch bei den NOAKs Dabigatran, Apixaban und Edoxaban auftreten. Randomisierte Studien und Register, die Patienten mit AF oder venöser Thromboembolie eingeschlossen haben, sollten unter diesem Gesichtspunkt ausgewertet werden. Es sollten Empfehlungen ausgearbeitet werden für die Antikoagulation in Situationen, in denen die Therapie mit NOAKs unterbrochen oder beendet wird.

Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 302–306

Keywords

Non-vitamin K-antagonist - oral anticoagulants - rivaroxaban rebound phenomenon - atrial fibrillation - pulmonary embolism

Schlüsselwörter

Nicht Vitamin K-Antagonisten - orale Antikoagulantien - Rivaroxaban - Rebound-Phänomen - Vorhofflimmern - Pulmonalembolie

 

Conflicts of interest

The authors declare that they have no conflicts of interest.

• References

• 1 Patel MR. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891.
• 2 Bauersachs R. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510.
• 3 Buller HR. et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297.
• 4 bUnited States Food and Drug Administration. XARELTO (Rivaroxaban) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202439s021lbl.pdf Initial U.S. Approval: 2011
• 5 Patel MR. et al. Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). J Am Coll Cardiol 2013; 61 (06) 651-658.
• 6 Caprini JA. Risk assessment as a guide to thrombosis prophylaxis. Curr Opin Pulm Med 2010; 16 (05) 448-452.
• 7 Perzborn E. et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59–7939 – an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 03 (03) 514-521.
• 8 Konstantinides SV. et al. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). European Heart Journal 2014; 35: 3033-3080.
• 9 Mahaffey KW. et al. End of study transition from study drug to open-label vitamin K antagonist therapy: the ROCKET AF experience. Circ Cardiovasc Qual Outcomes 2013; 06 (04) 470-478.
• 10 Bakhit A. et al. Rebound thrombosis within 24hours after interruption of therapy with rivaroxaban. Int J Cardiol 2016; 212: 235-236.
• 11 bUnited States Food and Drug Administration. ELIQUIS (Apixaban) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf Initial U.S. Approval: 2012
• 12 bUnited States Food and Drug Administration. SAVAYSA (Edoxaban) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf Initial U.S. Approval: 2015
• 13 Eriksson BI. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 05 (11) 2178-2185.
• 14 Hermans C, Claeys D. Review of the rebound phenomenon in new anticoagulant treatments. Curr Med Res Opin 2006; 22 (03) 471-481.
• 15 Thorne KM, Dee S, Jayathissa S. Thrombotic events after discontinuing dabigatran: rebound or resumption?. BMJ 2012; 345: e4469.
• 16 Vene N. et al. Risk of Thromboembolic Events in Patients with Non-Valvular Atrial Fibrillation After Dabigatran or Rivaroxaban Discontinuation – Data from the Ljubljana Registry. PLoS One 2016; 11 (06) e0156943.
• 17 Genewein U. et al. Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. Br J Haematol 1996; 92 (02) 479-485.
• 18 Haynes LM, Orfeo T, Mann KG. Rivaroxaban delivery and reversal at a venous flow rate. Arterioscler Thromb Vasc Biol 2012; 32 (12) 2877-2883.
• 19 Caprini JA, Merli GJ, Bhatt DL. Update on Risk Factors for Venous Thromboembolism. http://www.venousdisease.com/Publications/Update%20on%20risk%20factors-caprini.pdf Am J Med. 2005.
• 20 Nash R, Randhawa N, Saeed SR. Venous thromboembolism prophylaxis in ENT surgery: a survey of current practice. J Laryngol Otol 2015; 129 (02) 164-167.
• 21 Chiesa CEstomba. et al. The risk of venous thromboembolism in ENT and head & neck surgery. Otolaryngol Pol 2015; 69 (03) 31-36.
• 22 Guyatt GH. et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl. 02) 7S-47S.
• 23 Kowalewski M. et al. Meta-analysis of uninterrupted as compared to interrupted oral anticoagulation with or without bridging in patients undergoing coronary angiography with or without percutaneous coronary intervention. Int J Cardiol 2016; 223: 186-194.
• 24 Douketis JD. et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med 2015; 373 (09) 823-833.
• 25 Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012; 120 (15) 2954-2962.
• 26 Heidbuchel H. et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 34 (27) 2094-2106.
• 27 Levy JH. Discontinuation and Management of Direct-Acting Anticoagulants for Emergency Procedures. Am J Med 2016; 129 (11S): S47-S53.
• 28 Alvarez GF, Bihari D, Collins D. Heparin-induced thrombosis with a normal platelet count. Crit Care Resusc 2007; 09 (01) 51-53.