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

Chiasakul, Thita; Crowther, Mark; Cuker, Adam

doi:10.1016/j.rpth.2023.100107

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…A related meta-analysis reviewed 25 studies that assessed fixed and variable PCC dosing strategies. 8 The meta-analysis found no significant differences in hemostatic effectiveness, hromboembolic events, or mortality rates between the dosing strategies. Upon further review of the individual studies, there was less delineation between true fixed-dose and weight-based dosing strategies.…”

Section: Discussionmentioning

confidence: 87%

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal

Brett,

Taylor,

Pamela

et al. 2024

Clin Appl Thromb Hemost

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Background: Our institution introduced fixed-dose prothrombin complex concentrate (PCC) to streamline order verification and medication administration. Previous studies using fixed-dose PCC for vitamin K antagonist reversal showed comparable efficacy to weight-based dosing. Objective: To compare fixed versus weight-based PCC dosing for reversal of Factor Xa Inhibitor (FXaI) effects. Methods: Retrospective cohort study conducted at a tertiary care academic medical center. Patients who received PCC to reverse the effects of apixaban or rivaroxaban were eligible. Subjects in the fixed-dose group (5000 units or 2000 units) were compared to weight-based PCC (50 units/kg). The primary outcome was time between order entry and medication administration. Secondary outcomes included: average PCC dose, postadministration procedures, achieved hemostasis, 30-day mortality, hospital length of stay, and adverse drug events. Results: 72 patients received fixed-dose PCC and 101 received weight-based PCC. Median time between order entry and administration was 4.5 min shorter in the fixed-dose group compared to weight-based (34.5 vs 39 min, P = .10). In patients who received fixed-dose, 79.2% achieved hemostasis versus 71.3% in the weight-based group (RR = 1.11, 95% CI = 0.94-1.32). There was no difference in the number of subsequent hemorrhage-related surgeries (29.2% vs 36.7%, RR = 0.80, 95% CI = 0.51-1.24) or mortality rate (26.4% vs 35.6%, RR = 0.73, 95% CI = 0.46-1.17). There were zero adverse drug events reported. Rates of thrombosis were 2.8% and < 1% ( P = .57) in the fixed and weight-based groups, respectively. Conclusion and Relevance: The fixed-dosing strategy did not reduce time to PCC administration nor impact hemostasis or mortality. These data support that the fixed-dosing method is a viable option.

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Section: Discussionmentioning

confidence: 87%

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal

Brett,

Taylor,

Pamela

et al. 2024

Clin Appl Thromb Hemost

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“…4F-PCC has been shown to effectively restore hemostasis in factor-Xa inhibitor-related hemorrhage through elevation of coagulation factor levels and counteraction of factor-Xa inhibitor anticoagulation effects. [31][32][33][34] Most data are retrospective, so patient baseline characteristics vary and do not lead to exclusion from studies. In a recent meta-analysis by Chiasakul et al comparing fixed and weight-based 4F-PCC dosing, hemostatic effectiveness of 4F-PCC in factor-Xa inhibitor reversal was 81.0% for weight-based or variable dosing in comparison with 72.9% in the single fixed dosing study being analyzed, though there was moderate to high heterogeneity between studies.…”

Section: Discussionmentioning

confidence: 99%

“…6 The risk of thrombosis with repeat administration of concentrated factor product often can outweigh the benefit of additional factor given, particularly as there is data demonstrating use of fixed 4F-PCC dosing as noninferior to weight-based dosing. 31 In addition to the 4F-PCC, this patient also received 1 unit of platelets. At this time, his INR was 2 and his aPTT was 33.2 seconds.…”

Section: Casementioning

confidence: 99%

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Co-administration of Four-Factor Prothrombin Complex Concentrate With Andexanet alfa for Reversal of Nontraumatic Intracranial Hemorrhage

Pathan

2024

Hosp Pharm

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Objective: Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who receive both andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC). The aim of this case series is to evaluate the safety and efficacy outcomes in patients receiving the two agents in combination. Methods: Electronic medical records of patients who received both 4F-PCC and andexanet alfa for nontraumatic intracranial hemorrhage from January 2019 to March 2022 were retrospectively reviewed. Hemostatic efficacy and complications related to concurrent use of 4F-PCC with andexanet alfa were documented. Results: Nine patients received 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated intracranial bleeding, eight of whom required reversal of apixaban. Of these nine patients, five patients died within 28 days for a 56% incidence of mortality. The average time from 4F-PCC administration to andexanet alfa administration was 3 hours and 9 minutes. Most doses of andexanet alfa were given for concern for bleed expansion after 4F-PCC administration. Hemostatic efficacy based on stability of repeat computed tomography scans post-administration of both agents was found in six patients (66.67%), with a 55.56% n incidence of thromboembolism, including two pulmonary embolisms, two deep vein thromboses, and one renal artery thrombosis. Conclusion: Risks and benefits should be weighed to determine if there is benefit to adding andexanet alfa to 4F-PCC in patients with incomplete hemostasis and life-threatening hemorrhage. The combination of andexanet alfa and 4F-PCC may increase the risk of thrombotic complications without improving mortality.

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“…The optimal PCC dosing strategy for the management of FXaI-associated bleeding remains uncertain ( Table 1 ). 53 Prior cohort studies have employed either fixed PCC dosing (1,500–2,000 IU) 7 8 or weight-based dosing (50 IU/kg). 54 The underlying biological rationale underpinning fixed PCC dosing for FXaI-associated bleeding is unclear.…”

Section: Discussionmentioning

confidence: 99%

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale

Shaw

Unachukwu

Cyr

et al. 2023

TH Open

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Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain. Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery. Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC. Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

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

Cited by 7 publications

References 57 publications

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal

Co-administration of Four-Factor Prothrombin Complex Concentrate With Andexanet alfa for Reversal of Nontraumatic Intracranial Hemorrhage

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale

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