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  • Luo C
  • Chen F
  • Chen YH
  • Zhao CF
  • Feng CZ
  • et al.
Eur Rev Med Pharmacol Sci. 2021 Mar;25(6):2637-2653 doi: 10.26355/eurrev_202103_25428.

There are potential concerns related to bleeding caused by oral anticoagulants, especially in the elderly. Andexanet alfa has been authorized for use to reverse the effects of oral anticoagulants. Off-label use of four factor prothrombin complex concentrate (4F-PCC) for the reversal of oral factor Xa inhibitors is common. However, not much is known about their efficacy and safety profile. The intent of this meta-analysis was to evaluate the efficacy and safety of 4F-PCC and andexanet alfa for management of major bleeding due to oral factor Xa inhibitors. Comprehensive searches were done systematically through PubMed, Scopus and Google scholar databases. Studies that were retrospective record based or adopted prospective cohort approach and reported either of the three main outcomes, i.e., achieved hemostasis rate or rate of thrombotic events or mortality rate were included in the meta-analysis. Statistical analyses were done using STATA version 13.0. A total of 22 studies were included in the meta-analysis. All the studies had a single arm with no control/comparator group. The pooled rate of good to excellent hemostatic control upon use of andexanet was 80% (95% CI; 72% to 88%) and for 4F-PCC, it was 76% (95% CI; 70% to 83%). A comparatively higher pooled rate of thrombotic complications upon use of andexanet [13% (95% CI; 5% to 20%) was noted, compared to use of aPCC/4F-PCC [4% (95% CI; 3% to 5%). The pooled all-cause mortality rate within 30 days of administration was 24% (95% CI; 12% to 35%) with andexanet use and 19% (95% CI; 14% to 25%) for aPCC/4F-PCC. The findings suggest that use of both andexanet and aPCC/4F-PCC achieves a good hemostasis but there is an associated risk of thrombotic events and mortality. Future studies should have a control group to better establish evidence on efficacy and safety of these agents.

  • Wang D
  • Wang HY
  • Luo ZY
  • Pei FX
  • Zhou ZK
  • et al.
J Bone Joint Surg Am. 2019 Mar 6;101(5):438-445 doi: 10.2106/JBJS.18.00128.

Previous studies have confirmed that, compared with intravenous and intra-articular formulations, oral tranexamic acid (TXA) provides equivalent reduction in blood loss, at a substantially reduced cost and greater ease of administration. However, the optimal oral dosage regimen to achieve maximum blood-loss reduction remains unclear. The aim of this study was to assess the efficacy of a regimen of multiple doses of oral TXA on blood loss in primary total hip arthroplasty.


In this randomized controlled trial, 200 patients were randomized to 1 of 4 interventions. Group A received a single dose of 2.0 g of TXA orally at 2 hours preoperatively. In addition to this same preoperative dose, Group B received 1.0 g of TXA orally at 3 hours postoperatively, Group C received 1.0 g of TXA orally at 3 and 9 hours postoperatively, and Group D received 1.0 g of TXA orally at 3, 9, and 15 hours postoperatively. All patients received a 1.0-g topical dose of TXA. The primary outcome was total blood loss. Secondary outcomes included hemoglobin reduction, transfusion rate, thromboembolic complications, and adverse events.


The mean total blood loss (and standard deviation) was significantly less in Groups B, C, and D (792.2 ± 293.0, 630.8 ± 229.9, and 553.0 ± 186.1 mL, respectively) than in Group A (983.6 ± 286.7 mL) (p < 0.001). Moreover, Groups C and D had a lower mean reduction in hemoglobin than did Groups A and B. However, no differences were identified between Groups C and D for blood loss and hemoglobin reduction. Additionally, no differences were observed among the groups regarding thromboembolic complications and transfusions.


The multiple postoperative doses of oral TXA further reduced blood loss compared with a single preoperative bolus. The regimen of a preoperative dose and 3 postoperative doses of oral TXA produced maximum effective reduction of blood loss in total hip arthroplasty.


Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.