Treatment of apixaban- and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate

Sheikh-Taha, Marwan

doi:10.1007/s11739-018-1977-9

Cited by 42 publications

(34 citation statements)

References 15 publications

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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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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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“…Data from the large phase III RCTs demonstrated that outcomes of bleedings under DOACs were similar than in the VKA arm with similar treatment used (including PCC/aPCC) [2]. In addition, several observational studies in patients mayor DOAC-associated bleeding have been published, suggesting that (a)PCCs seems to be efficacious in supporting haemostasis [2, 14, 15]. Among them, edoxaban effects on bleeding following punch biopsy and reversal by a 4F-PCC was investigated in 110 subjects, suggesting that a dose of 50 IU/kg 4F-PCC may be suitable for reversing edoxaban anticoagulation [16].…”

Section: Non-specific Reversal Agent: Pcc and Activated Pccmentioning

confidence: 99%

Reversal agents for oral anticoagulant-associated major or life-threatening bleeding

Moia

Squizzato

2019

Intern Emerg Med

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Oral anticoagulants (OA) are effective drugs for treating and preventing the formation of blood clots in patients with atrial fibrillation, mechanical heart valves and venous thromboembolism but their therapeutic effect is always counterbalanced by an increased risk of bleeding. Direct oral anticoagulants (DOACs) have brought advantages in the management of many patients, with evidence of a lower risk of intracranial bleeding in comparison to vitamin K antagonists (VKAs). However, due to the increased number of anticoagulated patients worldwide, major and life threatening OA-related bleeding is also increasing, and effective reversal strategies are needed. We reviewed the reversal strategies for both VKAs and DOACs in the light of the latest evidence and recent guidelines, taking into account non-specific methods with fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) or four factor PCC, as well as specific reversal antidotes that are already approved or in approval phase. Most published studies on OA reversal have drawbacks, such as lacking a control arm or data on clinically relevant outcomes, and current guidelines’ recommendations are mainly based on panellists’ judgment. There is an urgent need for well-designed studies in this field. In the meanwhile, to improve the correct use of available resources and patients’ outcomes, we suggest a seven-element bundle for an optimal management of OA-associated major bleeding, including the implementation of fast turnaround time for laboratory tests in emergency, i.e. INR and DOAC plasma levels, and to build up a ‘bleeding team’ that includes experts of hemostasis, lab, trauma, emergency medicine, endoscopy, radiology, and surgery in every hospital.

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“…Hemostasis rates were consistent with previously reported literature. 8,15,19,20 The addition of a comparator group (eg, warfarin) in our study allowed for a frame of reference to be available, unlike prior studies that analyzed 4F-PCC use in fXa inhibitor-induced bleeding. This is important as 4F-PCC is generally considered the treatment of choice for warfarin-related bleeding, but guideline recommendations are more heterogeneous when it comes to recommending 4F-PCC for fXa-inhibitor-related bleeding due to a paucity of evidence guiding treatment decisions.…”

Section: Discussionmentioning

confidence: 99%

“…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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Treatment of apixaban- and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate

Cited by 42 publications

References 15 publications

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

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

Reversal agents for oral anticoagulant-associated major or life-threatening bleeding

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

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