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. 2023 Mar 10;7(2):100107.
doi: 10.1016/j.rpth.2023.100107. eCollection 2023 Feb.

Four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-associated bleeding: a meta-analysis of fixed versus variable dosing

Thita Chiasakul  1 , Mark Crowther  2 , Adam Cuker  3
Affiliations

Four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-associated bleeding: a meta-analysis of fixed versus variable dosing

Thita Chiasakul et al. Res Pract Thromb Haemost. .

Abstract

Background: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) to treat oral factor Xa (FXa) inhibitor-associated bleeding has not been established.

Objectives: To evaluate the effectiveness and safety of fixed versus variable 4F-PCC dosing for the management of FXa inhibitor-associated bleeding.

Methods: A systematic literature search and meta-analysis of clinical studies was performed using PubMed, Embase, and Cochrane databases from inception to January 2022. The primary outcomes included hemostatic effectiveness, mortality, and thromboembolic events. Secondary outcomes included 4F-PCC usage, total length of stay in hospital and in intensive care units, and time to 4F-PCC administration. The pooled incidence or mean was calculated using a random-effects model and compared between the 2 dosing strategies.

Results: Twenty-five studies were included and data from 1,760 patients (fixed dosing, n = 228; variable dosing, n = 1,532) were analyzed. There were no significant differences in hemostatic effectiveness, thromboembolic events, or mortality rates between the dosing strategies. Hospital length of stay was significantly longer in the fixed-dosing group, with a mean stay of 7.4 days (95% CI: 3.6-11.1) compared to 5.9 days (95% CI: 5.5-6.3) in the variable-dosing group (P < 0.001). The mean initial 4F-PCC dose was significantly higher with variable dosing than fixed dosing (38 IU/kg; 95% CI: 32-44 vs. 27 IU/kg; 95% CI: 26-28, P < 0.001).

Conclusions: A fixed-dosing strategy appears to be a safe and effective alternative to variable weight-based dosing and was associated with lower 4F-PCC usage. However, direct comparative studies are needed to confirm these results.

Keywords: anticoagulants; anticoagulation reversal; factor Xa inhibitors; hemostasis; prothrombin complex concentrates.

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Figures

Figure 1
Figure 1
PRISMA flow diagram. ∗Including 67 original articles, 382 conference abstracts, and 49 other records (reviews, letters etc.) ∗∗382 abstracts from Embase were screened only based on the title †Reports could not be found.
Figure 2
Figure 2
Forest plot of the hemostatic effectiveness in patients receiving fixed-dose 4F-PCC in comparison with variable-dose strategy. CT, computer tomography; ES, effect size.
Figure 3
Figure 3
Forest plot of A) thromboembolic events and B) mortality rates in patients receiving fixed or variable doses of 4F-PCC. ES, effect size.
Figure 4
Figure 4
Forest plot of A) hospital and B) ICU LOS in patients receiving fixed or variable doses of 4F-PCC. ES, effect size; ICU, intensive care unit; LOS, length of stay.
Figure 5
Figure 5
Forest plots of A) Mean 4F-PCC dose and B) Total 4F-PCC dose in patients receiving a fixed or variable doses of 4F-PCC. ES, effect size.
Supplementary Fig S1
Supplementary Fig S1
Supplementary Fig S2
Supplementary Fig S2
Supplementary Fig S3
Supplementary Fig S3
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