Another new and novel anticoagulant that is gaining great traction is Rivaroxaban. This inhibitor of factor Xa is currently approved in Canada for prevention of venous thromboembolism following major hip or knee surgery. It is also gaining ground in off label uses specifically for prophylaxis of stroke in atrial fibrillation, and while this is not yet an approved indication there early studies showing non-inferiority to Coumadin, with similar (possibly better) profile of bleeding risk.
Like all anticoagulants the downside is the bleeding risk. A friend of mine, involved with an early trial of Rivaroxaban vs. placebo put it this way; ‘The trial was blinded but the Rivaroxaban patients all had a little trail of blood following them around.’ While this is an exaggeration it is also a reminder that whenever a new anticoagulant becomes available we must also adapt new strategies to treat resulting bleeding complications.
Rivaroxaban is the first commercially available oral inhibitor of Factor Xa in Canada. It has excellent GI absorption and it’s inhibition of Xa lasts up to 24 hours allowing easy dosing. Per the manufacturers suggestions there is no need for dose adjustments nor for monitoring of coagulation parameters. Metabolism and excretion are mixed with about half of the drug excreted unchanged in urine and feces and half metabolized prior to excretion. The drug is contraindicated in patients with moderate to severe renal impairment (Creatinine clearance less than 15ml/min) moderate to severe hepatic impairment, elevated INR, or with azole antifungals or HIV protease inhibitors.
The bleeding patient who is currently on Rivaroxaban presents a particular challenge. There is limited data suggesting that prothrombin complex concentrate (which contains factor X) and recombinant factor VIIa may have a role in patients with life threatening bleeding.
As we discussed in Part 1: Dabigatran, it is imperative that these patients receive early consultation (likely phone consultation) with a hematologist as well as meticulous treatment for all elements of their bleeding. Whenever possible early surgical, endoscopic or interventional radiology control of the bleeding site should be obtained. Resuscitation with balanced blood products rather than crystalloids is likely warranted. Correction of hypothermia and acidosis is of upmost importance, and the presence of other anticoagulants (ASA, clopedigrel, etc.) or auto-anticoagulation (liver disease) should be considered and corrected.
In spite of meticulous care and attempted reversal with PCC or rFVIIa some of these patients will continue to bleed and will have poor outcomes.