In this episode, I’ll discuss the effects of giving both andexanet alfa AND 4-factor prothrombin complex concentrate.
There is scant literature on patient outcomes when both Four-factor prothrombin complex concentrate plus andexanet alfa are used for reversal of factor Xa inhibitor–associated bleeding.
There are no guideline recommendations that suggest using both Four-factor prothrombin complex concentrate and andexanet alfa for reversal of factor Xa inhibitor–associated bleeding. Many institutions only use 4FPCC. Some institutions, such as the one the authors of the case series practice at, use andexanet alfa only if hemostasis after 4FPCC is inadequate.
Patient #1 was taking rivaroxaban 15 mg daily and presented with intraparenchymal and intraventricular hemorrhage. They received 42 units/kg of 4FPCC and, after hemostasis was judged to be inadequate, high dose andexanet alfa. This patient died in the hospital on day 1 and experienced a STEMI.
Patient #2 was taking apixaban 5 mg twice daily and presented with subdural hematoma. They received 25 units/kg of 4FPCC and, after hemostasis was judged to be inadequate, low dose andexanet alfa. This patient died in the hospital on day 12 after experiencing an internal carotid artery and middle cerebral artery infarct on hospital day 10.
Patient #3 was taking apixaban 5 mg twice daily and presented with intraparenchymal hemorrhage. They received 20 units/kg of 4FPCC and, after hemostasis was judged to be inadequate, low dose andexanet alfa. This patient died in the hospital on day 8 but did not experience any thrombotic complications.
Patient #4 was taking rivaroxaban 20 mg daily and developed a hemopericardium. They received 30 units/kg of 4FPCC and, after hemostasis was judged to be inadequate, high dose andexanet alfa. After a 5 day hospital stay the patient was discharged home.
Patient #5 was taking rivaroxaban 20 mg daily and developed a sternal hematoma. They received 30 units/kg of 4FPCC and, after hemostasis was judged to be inadequate, high dose andexanet alfa. After a 3 day hospital stay the patient was discharged to a rehab facility.
The authors also conducted a review of literature and databases and found a total of 23 reported cases of safety outcomes with patients who received both andexanet alfa and 4F-PCC. The overall incidence of thromboembolism was 35% (8 of 23 cases).
Even with this publication, there is little data on this combination of reversal agents. The authors suggest clinicians should be cautious when considering the use of both agents after carefully weighing risks and benefits. While the benefit does not seem impressive, and the risk of thrombotic complication seems high, if a patient has a life-threatening bleed and inadequate hemostasis after 4FPCC, there will often be a desire to give andexanet alfa if it is available rather than just supportive care.
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