Reversal of factor Xa inhibitors associated intracranial haemorrhage at a tertiary medical centre

Abstract

Prior to the approval of andexanet, there were no FDA-approved reversal agents indicated for the treatment of factor Xa inhibitor (FXaI) associated major bleed. Four-factor prothrombin complex concentrate (4F-PCC) has been widely used off-label for FXaI-associated bleeding. The purpose of this study was to compare the effectiveness and safety of andexanet and 4F-PCC for the reversal of FXaI-associated intracranial haemorrhage. The primary end point is in-hospital mortality; secondary endpoints include haemostatic efficacy and safety. This study is a singlecentre, retrospective chart review, including patients admitted between 1 January 2016 and 15 August 2019, who received 4F-PCC or andexanet for the management of FXaI-associated intracranial haemorrhage. Of the 45 patients included in this study, 23 patients were in the andexanet group and 22 were in the 4F-PCC group. At index admission, mean age was 76 years and the majority of patients (64%) were on apixaban with 33% presented with Glasgow Coma Scale 24 (GCS) score less than 12. At hospital discharge, 47% of patients in the andexanet group had died or discharged to hospice compared with 45% in the 4F-PCC group. No thromboembolic events were observed in either group within 5 days after administration of the reversal agent. The results of this study suggest that haemostasis and mortality at discharge during the index hospitalization appears to be similar between groups. Prospective randomized control trials comparing safety and efficacy of andexanet and 4F-PCC are needed.

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

“…After the exclusion of these 2 studies, the data on the comparison of 4F-PCC and AA were derived from 8 retrospective studies. [35][36][37][39][40][41][42]44 We found that 4F-PCC had a comparable proportion of successful…”

“…Several other smaller studies have shown the use of 4F-PCCs as a viable reversal option for DOAC-related ICH for anticoagulation reversal (reversal rates, 54.5%-94.7%) and safety (mortality rates, 4.7%-63.6%; thrombotic event rate, 0%-17.2%). 8 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 Albeit with significant heterogeneity, our meta-analysis found a combined proportion of anticoagulation reversed of 77%, a mortality rate of 26%, and a thromboembolic event rate of 8% ( Figures 1 - 3 ).…”

“…Thirty-six studies were included in the meta-analysis (eAppendix 1 in the Supplement ). Twenty-two studies with 967 participants evaluated 4F-PCC for reversal 8 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ; 17 studies with 525 participants evaluated AA 13 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ; and 5 studies with 340 participants evaluated idarucizumab, 12 , 53 , 54 , 55 , 56 consisting of a total of 1832 patients with ICH while receiving treatment with a DOAC. Eight studies had data on more than 1 agent.…”

“…Eight studies had data on more than 1 agent. 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 The characteristics of the studies are in the Table and eAppendix 3 in the Supplement .…”

“…After the exclusion of these 2 studies, the data on the comparison of 4F-PCC and AA were derived from 8 retrospective studies. 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 We found that 4F-PCC had a comparable proportion of successful anticoagulation reversal (RR, 0.95; 95% CI, 0.85-1.06; I 2 = 0%; 95% CI, 0%-75%), proportional mortality (RR, 1.40; 95% CI, 0.68-2.86; I 2 = 65%; 95% CI, 17%-86%), and thromboembolic event rate (RR, 0.89; 95% CI, 0.36-2.21, I 2 = 0%; 95% CI, 0%-79%) when used for the reversal of FXaI in patients with ICH ( Figure 4 ).…”