A 76-year-old male presents to the Emergency Department with sudden onset of intense (10/10) sharp chest pain radiating to the neck and shoulders beginning approximately 45 minutes ago and associated with diaphoresis and dyspnea. He has a past medical history significant for hypertension, heart failure with preserved ejection fraction, hyperlipidemia, and atrial fibrillation. The outpatient medications include amlodipine 10mg daily, atorvastatin 40mg daily, lisinopril 40mg daily and rivaroxaban 20mg daily, all of which he last took about 4 hours ago.
A CT scan of the chest confirms a Type A aortic dissection beginning superior to the coronary arteries and extending to the level of the renal arteries. After reviewing these findings and discussing the management options with the patient, the decision is made to proceed urgently to the operating room for definitive management.
In addition to supportive measures, which of the following therapeutic interventions may help reduce his risk of bleeding?
Show Answer
The correct answer is: C. Prothrombin complex concentrates
Discussion
Novel oral anticoagulants (NOACs) have been shown to have improved or comparable efficacy and safety when compared with standard dose warfarin among patients with atrial fibrillation. These medications offer a predictable anticoagulant effect and thus do not require ongoing monitoring. However, there are no specific antidotes for NOACs.
For patients undergoing planned surgical intervention, the risk of stroke and the risk for bleeding must be weighed and the NOAC can be held as deemed appropriate for 12-48 hours (see Table 1 below).1 For patients who require more urgent surgery, intervention should be deferred for at least 12 and ideally 24 hours after the last dose.
In our case, when immediate surgical intervention is required to address a life-threatening condition such as aortic dissection, adjunctive treatment to decrease the risk of bleeding may be required. Rivaroxaban, an oral Factor Xa inhibitor, has a half-life of 5-9 hours in younger patients and those with normal renal function and 11-13 hours in more elderly patients and those with impaired renal function. It is primarily excreted renally but is extensively protein-bound (95%).2
Administration of vitamin K enables more rapid regeneration of Factor II, VII, IX, and X and can be used to reverse the effects of warfarin. Oral vitamin K is safer than intravenous administration, which is associated with anaphylaxis, but neither achieves immediate reversal of warfarin-based anticoagulant effect.
Aside from the time delays inherent in performing hemodialysis, which are inappropriate given the patient's Type A aortic dissection, rivaroxaban is extensively protein-bound and therefore is not efficiently removed with hemodialysis. In an open-label study of patients with end stage renal disease on hemodialysis, it was estimated that 62% of dabigatran could be removed within 2 hours of administration.3
If an anticoagulant was recently ingested, activated charcoal can be attempted. However, in our case, the last dose of rivaroxaban was taken 4 hours ago and thus charcoal is unlikely to be effective.
There is some evidence to support the use of prothrombin complex concentrates (PCC) in this situation. There are two types of PCCs — 3-factor formulations which contain Factors II, IX, and X or 4-factor formulation which also includes Factor VII. They can provide a large concentration of Factor X and thus overwhelm the inhibitory effect of rivaroxaban.4 In a randomized, double-blind, placebo-controlled study of 12 volunteers who were treated with rivaroxaban 20mg twice daily or dabigatran 150mg twice daily, administration of 50IU/kg of PCC was shown to effectively reverse the anticoagulant effect of rivaroxaban as assessed by the activated prothrombin time.5
References
Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. Oct 11 2012;120(15):2954-2962.
Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clinical pharmacokinetics. Apr 2010;49(4):259-268.
Battinelli EM. Reversal of New Oral Anticoagulants. Circulation. October 4, 2011 2011;124(14):1508-1510.
Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects. Circulation. October 4, 2011 2011;124(14):1573-1579.
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