Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products

Abstract

To analyze the efficacy and safety of activated prothrombin complex concentrates (aPCC) and four-factor prothrombin complex concentrates (4F-PCC) to prevent hematoma expansion in patients taking apixaban or rivaroxaban with intracranial hemorrhage (ICH). In this multicenter, retrospective study, sixty-seven ICH patients who received aPCC or 4F-PCC for known use of apixaban or rivaroxaban between February 2014 and September 2018 were included. The primary outcome was the percentage of patients who achieved excellent/good or poor hemostasis after administration of aPCC or 4F-PCC. Secondary outcomes included hospital mortality, thromboembolic events during admission, and transfusion requirements. Excellent/good hemostasis was achieved in 87% of aPCC patients, 89% of low-dose 4F-PCC [< 30 units per kilogram (kg)], and 89% of high-dose 4F-PCC (≥ 30 units per kg). There were no significant differences in excellent/good or poor hemostatic efficacy (p = 0.362). No differences were identified in transfusions 6 h prior (p = 0.087) or 12 h after (p = 0.178) the reversal agent. Mortality occurred in five patients, with no differences among the groups (p = 0.838). There were no inpatient thromboembolic events. Both aPCC and 4F-PCC appear safe and equally associated with hematoma stability in patients taking apixaban or rivaroxaban who present with ICH. Prospective studies are needed to identify a superior reversal agent when comparing andexanet alfa to hospital standard of care (4F-PCC or aPCC) and to further explore the optimal dosing strategy for patients with ICH associated with apixaban or rivaroxaban use.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

“…and factor Xa inhibitors. [169][170][171] RRT may reduce dabigatran concentration. 177 In patients on heparin, protamine reverses the anticoagulant effect.…”

Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis

“…The level of evidence supporting these 4F-PCC dosing recommendations are generally acknowledged as low (based on studies assessing the correction of anticoagulant-induced laboratory abnormalities or punch biopsy studies) and the strength of recommendations deemed weak [31,33,35,37]. Multiple studies comparing the hemostatic effectiveness of lower (25 u/kg, < 30 u/kg, or < 35 u/kg) and higher (≥ 30 u/kg, ≥ 35 u/kg, or 50 u/kg) 4F-PCC doses have failed to show significant differences between dosing strategies [38][39][40]. Fourth, as this was not a randomized controlled trial, the risk of confounding bias exists [38].…”

A meta‐analysis of andexanet alfa and prothrombin complex concentrate in the treatment of factor Xa inhibitor–related major bleeding

“… b The criteria for effective hemostasis used in Annexa‐4 are adjusted Sarode criteria and included in Appendix S2 38 …”