Who should attend:

• Clinical faculty from the University of Pittsburgh School of Pharmacy
• Clinical staff pharmacists employed by the University of Pittsburgh Medical Center and deployed throughout the hospital campus in unit based roles and centrally in the department of pharmacy's main pharmacy
• Student pharmacy interns currently working within the department of pharmacy
• Certified Pharmacy Technicians

Over 3.5 million patients in the United States take one of the direct oral anticoagulants (DOACs). Adverse side effects of this medication include serious bleeding events, such as intracranial hemorrhage (ICH) and gastrointestinal bleeds. Patients who experience an anticoagulant-related ICH are more likely to have larger initial hematoma volumes, greater rates of hemorrhagic expansion, neurologic deterioration, and are at a three- to four-fold increased risk of mortality when compared to patients who are not on these medications. Anticoagulant-related intracranial hemorrhage is a medical emergency and rapid reversal is key to mitigate the increased risks in this patient population.

Best practices for reversal involve obtaining a timely medical history on the patient to verify the following: anticoagulant agent, dose and frequency of the corresponding prescription, administration time of the last dose taken, and if there are any other agents are taken that may impact hemostasis. Indications for urgent reversal include acute, life-threatening hemorrhage in patients on active anticoagulation therapy, with confirmed ICH on imaging.

Initially, prothrombin complex concentrates (PCCs) were utilized to reverse DOACs. Now there are more targeted, anticoagulant-specific reversal agents available such as Andexanet alfa for the reversal of the oral factor Xa inhibitors apixaban and rivaroxaban, and idarucizumab, which neutralizes the oral direct thrombin inhibitor, dabigatran. Since Andexanet alfa came to market in 2018 as the first approved antidote for apixaban- and rivaroxaban-associated life-threatening bleeds, clinical controversy has surrounded whether Andexanet alfa (AA) or 4-Factor PCC (4-PCC) should be used for reversal of DOAC-associated ICH. Conflicting guideline recommendations based on low quality evidence and lack of head-to-head trials contribute to this debate. Specifically, unanswered questions from the literature include a lack of clear consensus on which agent to use preferentially in ICH as well as the dosing strategy to utilize.

Upon successful completion of this continuing pharmacy education program, the participant should be able to:

• Identify patients indicated for anticoagulation reversal in intracranial hemorrhage (ICH)
• Describe the utilization and limitations of reversal agents for direct oral anticoagulants (DOACs)
• Discuss literature regarding the efficacy and safety of both Andexanet alfa (Andexxa®) and 4-Factor Prothrombin Complex Concentrate (Kcentra®).

1. Troy A, Anderson TS. National Trends in Use of and Spending on Oral Anticoagulants Among US Medicare Beneficiaries From 2011 to 2019. JAMA Health Forum. 2021;2(7):e211693. doi:10.1001/jamahealthforum.2021.1693
2. O'Shaughnessy DF, Atterbury C, Bolton Maggs P, Murphy M, Thomas D, Yates S, Williamson LM, British Committee for Standards in Haematology, Blood Transfusion Task Force: Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol. 2004, 126: 11-28. 10.1111/j.1365-2141.2004.04972.x.
3. Andexxa (prescribing information). Boston, MA: Alexion Pharmaceuticals, Inc.; 2021.
4. Eliquis [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company, and New York, NY: Pfizer Inc.; 2019.
5. Xarelto [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020.
6. Chen S, Zeng L, Hu Z. Progressing haemorrhagic stroke: categories, causes, mechanisms and managements. J Neurol. 2014 Nov;261(11):2061-78.
7. Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011 Jun;42(6):1781-6.
8. An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017 Jan;19(1):3-10.
9. Meretoja A, Strbian D, Putaala J, et al. SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage. Stroke 2012; 43:2592.
10. Menon DK, Schwab K, Wright DW, et al. Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil 2010; 91:1637.

Joint Accreditation Statement - this statement supersedes any other statement on this page

In support of improving patient care, the University of Pittsburgh is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Pharmacy (CPE)

This knowledge-based activity provides 1.0 contact hours of continuing pharmacy education credit.

Other health care professionals will receive a certificate of attendance confirming the number of contact hours commensurate with the extent of participation in this activity.