In this episode, I’ll discuss an article about using prothrombin complex concentrates for the treatment of factor Xa inhibitor-related intracranial hemorrhage.
Article
Lead author: Nicholas G. Panos
Published in Circulation April 2020
Background
Much of the time that oral factor Xa (FXa) inhibitors have been on the market, there has been an absence of direct reversal agents. Prothrombin complex concentrates have been routinely used and recommended for serious bleeding events such as intracranial hemorrhage (ICH) in patients on oral factor Xa inhibitors. Even now with the availability of andexanet alfa, many institutions use prothrombin complex concentrates due to the lower relative cost. Many expert guidelines support using prothrombin complex concentrates (PCC) in patients with ICH based upon limited data. The authors of this study sought to evaluate the safety and efficacy of PCC for FXa inhibitor-related ICH in a large, multicenter cohort of patients.
Methods
The study was a multicenter, retrospective, observational cohort. All patients had apixaban or rivaroxaban-related ICH and received PCC. The study looked at both safety and hemostatic efficacy. The safety analysis looked at all patients meeting inclusion criteria for the occurrence of a thrombotic event. All patients with at least one follow-up brain imaging scan within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence.
Results
A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients had a follow-up brain imaging scan and were able to be assessed for hemostatic efficacy. Excellent or good hemostasis was observed in just over 80% of patients. There were 25 patients who experienced a thrombotic event for an occurrence rate of 3.8%. 22 of these events occurred in the first 14 days following PCC administration. For the full cohort of patients, in-hospital mortality was 19.0% and the median intensive care unit and hospital length of stay were 2.0 and 6.0 days, respectively.
Conclusion
The authors concluded:
Administration of PCC after apixaban and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCC in patients with FXa inhibitor-related ICH are needed.
Discussion
This study actually included two forms of PCC, 4-factor PCC known as KCentra and activated PCC. KCentra use was far more common with a ratio of about 3.5 to 1. The median initial dose of KCentra was 43.8 units/kg and the median initial dose for activated PCC was 26.7 units/kg. The median time from presentation to PCC administration was 2.6 hours, which seems like a considerable amount of time. Only 5% of patients needed a second dose. The thrombotic events included 14 DVTs, 8 ischemic strokes, 2 MIs, and 1 PE. All patients who had an ischemic stroke also had atrial fibrillation. This is the most comprehensive cohort study to date looking at the use of PCC to treat ICH from FXa inhibitors. Until a randomized trial is available this may be the best data we will have to go by on the use of PCC in clinical practice for treating ICH.
Members of my Hospital Pharmacy Academy have access to practical training material on DOAC Reversal, Warfarin Reversal, Heparin Reversal, Practical Strategies for Acutely Elevated ICP, Tranexamic Acid in Treatment of Bleeding, ICH After Alteplase, Blood Pressure Control in Acute Stroke, and the Pharmacist’s Role at a Stroke Alert. I’ve created this material as well as many more resources in the Academy to help hospital pharmacists learn practical critical care and hospital pharmacy skills and translate theoretical knowledge to the bedside. To get immediate access to everything the Academy has to offer go to pharmacyjoe.com/academy to join today.
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