Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage

Dybdahl, Daniel; Walliser, Grant; Spalding, M Chance; Pershing, Michelle L.; Kincaid, Michelle

doi:10.1016/j.ajem.2019.01.008

Cited by 21 publications

(24 citation statements)

References 13 publications

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“…Several observational cohort studies found that 4F-PCC at a dose range of 25-50 units/kg achieves effective hemostasis in 65% to 94.7% of patients with oral FXa inhibitor-associated ICH. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Comparatively, excellent or good hemostasis was achieved in 80% of patients treated with andexanet alfa in the ANNEXA-4 trial, with a corresponding 92% reduction in apixaban and rivaroxaban levels after administration. 32 However, ANNEXA-4 exclusion criteria may not be representative of true clinical practice, as ethical considerations arise when restricting therapy from those with known risk factors for hematoma expansion, such as larger ICH volume or low GCS score at presentation, or low probability of survival at 30 days.…”

Section: Discussionmentioning

confidence: 99%

“…13 Off-label use of 4F-PCC for this indication suggests effective hemostasis can be achieved in 65% to 94.7% of patients with oral FXa inhibitor-associated ICH. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Comparatively, andexanet alfa is a recombinant human FXa decoy protein that binds directly to rivaroxaban and apixaban to reverse their anticoagulant effect. 8 However, despite a reported 92% reduction in anti-FXa activity at the end of the andexanet alfa bolus administration, clinician concerns regarding its efficacy and superiority were raised given its short duration of action and noted limitations in the open-label single arm clinical trial.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

Barra

Das

Hayes

et al. 2020

Journal of Thrombosis and Haemostasis

100

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Background/Objective: Before approval of andexanet alfa, off-label treatment with 4-factor prothrombin complex concentrate (4F-PCC) was often utilized for the management of life-threatening hemorrhages associated with oral factor Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F-PCC. Methods:We performed a retrospective, single-center case series of rivaroxaban or apixaban-associated ICH between 2016-2019 treated with andexanet alfa or 4F-PCC. Good or excellent hemostatic effectiveness, good functional outcome (Glasgow Outcome Score [GOS]> 3) at hospital discharge, and incidence of thrombosis within 30 days were reported.Results: Eighteen patients were included in the andexanet alfa cohort and 11 in the 4F-PCC cohort. Excellent or good hemostasis occurred in 88.9% of andexanet alfa-treated patients and 60% of 4F-PCC-treated patients. Good functional outcome on discharge occurred in 55.6% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Thrombotic complications occurred in 16.7% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Median order-to-administration time was 1.1 hours [0.8-1.4] versus 0.5 hours [0.1-0.8] in the andexanet alfa and 4F-PCC group, respectively. The median cost of therapy was $29970/patient versus $6925/patient in the andexanet alfa and 4F-PCC group, respectively. Conclusions:We observed higher rates of occurrence of good or excellent hemostasis and GOS > 3 on hospital discharge and increased incidence of thrombosis in patients who received andexanet alfa compared to 4F-PCC for oral factor Xa inhibitor reversal.However, patients receiving 4F-PCC had lower pre-reversal Glasgow Coma Scale (GCS) score and larger pre-reversal ICH volume.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

Barra

Das

Hayes

et al. 2020

Journal of Thrombosis and Haemostasis

100

View full text Add to dashboard Cite

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“…On the full-text review, 14 case series met inclusion criteria for this systematic review without exclusions. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] An additional nine case series available as abstracts only were included in the sensitivity analysis only. [32][33][34][35][36][37][38][39][40] Characteristics of case series The impact factor of journals in which case series were published ranged from 0.0420 to 16.562 (median, 2.873) (online supplemental eTable 1).…”

Section: Literature Searchmentioning

confidence: 99%

Quality evaluation of case series describing four-factor prothrombin complex concentrate in oral factor Xa inhibitor-associated bleeding: a systematic review

et al. 2020

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IntroductionAs oral factor Xa (oFXa) inhibitor use has increased, so has publication of case series describing related bleeding managed with four-factor prothrombin complex concentrate (4F-PCC).ObjectiveThis review aimed to identify case series describing 4F-PCC management of oFXa inhibitor-related bleeding and appraise their methodological and reporting quality.DesignWe searched Medline and EMBASE (1 January 2011 to 31 May 2020) to identify series of ≥10 patients with oFXa inhibitor-related major bleeding given off-label 4F-PCC. Case series were evaluated using a validated tool adapted for this topic. The tool addressed patient selection, bleed/outcome ascertainment, causal/temporal association and reporting.ResultsWe identified 14 case series. None had ≥100 patients (range=13–84), three were prospective, two detailed appropriate inclusion criteria and four noted consecutive inclusion. While 12 series provided clear/appropriate methods for diagnosis of intracranial haemorrhage (ICH); none did so for extracranial bleeds and it was not clear whether bleeding was adjudicated in any. Haemostatic effectiveness, thrombosis and mortality were together evaluated in 12 series, but only seven used validated methods to evaluate/diagnosis haemostasis in ICH, six in gastrointestinal bleeds, five in other bleeds and three in thrombosis. Independent adjudication of haemostasis (n=1) and thrombosis (n=2) was infrequent. Thirty-day follow-up for mortality and thrombosis was noted in five and seven series. Anticoagulation measurement/levels in at least some patients were conveyed in three series. Few series provided data on anticoagulant agent/dose (n=4), time from anticoagulant (n=4), time-to-reversal (n=7), baseline (n=7) or change (n=0) in neurologic function.ConclusionsAlthough many case series describe off-label use of 4F-PCC for oFXa inhibitor-related bleeding, methodological flaws and/or poor reporting necessitates caution in interpretation.

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“…The limited data available are comprised of small, single-center studies that lack a comparator group. [14][15][16][17][18][19][20] The purpose of this study was to determine the hemostatic efficacy of 4F-PCC for the reversal of fXa inhibitor-related, life-threatening bleeding compared to 4F-PCC for warfarinrelated life-threatening bleeding.…”

Section: How Does This Improve Population Health?mentioning

confidence: 99%

Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding

2021

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Introduction: Factor Xa (fXa) inhibitor reversal for life-threatening bleeding is controversial due to a lack of high-quality evidence. The purpose of this study was to determine the hemostatic efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of fXa inhibitors compared to warfarin for life-threatening bleeding. Methods: This was a multicenter, retrospective cohort study at two academic medical centers between January 1, 2014-December 31, 2019, which included patients who presented to the emergency department with a life-threatening bleed necessitating anticoagulation reversal with 4F-PCC. The primary endpoint was achievement of hemostatic efficacy after 4F-PCC administration. Results: Of the 525 patients who had an order for 4F-PCC during the study period, 148 patients met the criteria for inclusion (n = 48 fXa inhibitor group; n = 100 warfarin group). Apixaban (52.1%) and rivaroxaban (45.8%) were the most commonly used fXa inhibitors. Effective hemostasis was similar between groups (79.2% fXa inhibitor group vs 85% warfarin group, p = 0.38). This was consistent across all types of bleeding. Thrombotic events were rare in both groups (2% vs 3%). Conclusion: This multicenter, retrospective cohort study demonstrated that using 4F-PCC for treatment of life-threatening bleeding produced effective hemostasis in patients on fXa inhibitors and warfarin. [

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Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage

Cited by 21 publications

References 13 publications

Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

Evaluation of andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) for reversal of rivaroxaban‐ and apixaban‐associated intracranial hemorrhages

Quality evaluation of case series describing four-factor prothrombin complex concentrate in oral factor Xa inhibitor-associated bleeding: a systematic review

Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding

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