In this episode, I’ll discuss current strategies for the reversal of life-threatening bleeding due to direct oral anticoagulants (DOACs).
This month marks the one-year anniversary of the Critical Care Pharmacy Academy. Over 200 pharmacists have joined the Academy to learn and enhance their critical care skills. Because many Academy members cross-cover areas of pharmacy beyond critical care, starting December 7 the Academy will become the Hospital Pharmacy Academy. In addition to critical care, Masterclass trainings in the areas of emergency medicine, infectious disease, and general hospital pharmacy will be added regularly.
The Hospital Pharmacy Academy will help you take your clinical pharmacy skills to the next level whether you are an experienced hospital pharmacist that wants to keep current and relevant in a competitive job market, or a pharmacist or resident looking to gain confidence and knowledge in hospital pharmacy practice! To learn more and get a video tour of inside the Hospital Pharmacy Academy go to pharmacyjoe.com/academy.
DOAC vs NOAC
Both the ISMP and The International Society on Thrombosis and Haemostasis suggest the use of the abbreviation DOAC to refer to anticoagulants such as apixaban, rivaroxaban, edoxaban, betrixaban, and dabigatran. This is because the term NOAC, although meant to stand for “Novel Oral AntiCoagulants” may be confused as standing for “No Anticoagulation.”
The current DOACs can be divided into two categories: direct thrombin inhibitors and factor Xa inhibitors.
When you are evaluating a patient with a life-threatening bleed who has recently taken a DOAC, the two most important pieces of information to consider are:
1. The time since the last dose.
2. The patient’s renal function.
This information can then be used to determine whether or not 5 half-lives of the DOAC have passed. After 5 half-lives of the DOAC have elapsed, there is likely no medication left to be reversed and the bleeding should be treated as if the patient was not on a DOAC.
You can find a calculator to estimate the time for 5 half-lives to elapse of the commonly used DOACs at pharmacyjoe.com/DOAC.
There are no placebo-controlled studies of the reversal of any of the DOACs that compare patient-focused outcomes such as mortality. Instead, the available data examine surrogate endpoints such as hemostasis or normalization of coagulation studies.
The only DOAC with an actual reversal agent approved by the FDA is the direct thrombin inhibitor dabigatran. Dabigatran may be reversed by giving 5 grams of idarucizumab by rapid IV administration. If the bleeding does not resolve in an appropriate amount of time, this dose may be repeated.
Idarucizumab comes in 2.5 g 50 mL vials, so 2 vials will be needed for each dose. Idarucizumab may be drawn up into a syringe and given by IV bolus or may be infused over 5 or 10 minutes. If idarucizumab is not in your smart pump library, infusing it at 600 mL/hr will administer each 50 mL vial over 5 minutes. Be sure to flush the IV tubing with normal saline as up to 50% of the last vial may be trapped in the tubing.
Factor Xa inhibitor reversal
The oral factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and betrixaban have no FDA approved reversal agent. Pro-hemostatic attempts may be made with various alternative agents such as:
1. 4-factor prothrombin complex concentrates (Kcentra) at a dose of 50 units/kg IV.
2. Activated prothrombin complex concentrates (FEIBA) at a dose of 50–100 units/kg IV.
3. Activated factor VII (Novoseven) at a dose of 90 μg/kg IV.
4. 3-factor prothrombin complex concentrates (Profilnine) at a dose of 50 units/kg IV.
5. Fresh frozen plasma.
These agents have not been rigorously studied for reversal of life-threatening bleeding in a patient on a factor Xa inhibitor. I prefer to use Kcentra over the other agents. Fresh frozen plasma appears to have limited effectiveness, and the agents with activated factors would theoretically have a much higher chance of causing a serious clot.
There are two additional reversal agents that may soon be FDA approved:
1. Andexanet Alfa reverses the effects of the factor Xa inhibitors. It was discussed in episode 121.
2. Ciraparantag which is a broad-spectrum reversal agent that reverses every anticoagulant except for warfarin. It was discussed in episode 75 and episode 173.
That's a great point, especially in areas where idarucizumab is not available!
— Pharmacy Joe ?? (@PharmacyJoe) December 5, 2017
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