Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606 Subjects

Hill, Robert L.; Han, Thang S.; Lubomirova, Irina; Math, Nikhil; Bentley, Paul; Sharma, Pankaj

doi:10.1007/s40265-019-01179-w

Cited by 12 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following administration of saline or 4F-PCC 50 IU/kg, no thrombus formation was observed at 30 minutes (Fig 4A and 4B). When the supratherapeutic dose of 4F-PCC 300 IU/kg was administered, thrombus formation with score 2 was observed in all animals at both 30 minutes and 6 hours, with median (range) thrombus wet weights of 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) mg and 22 (7-51) mg, respectively (Fig 4C and 4D), confirming prior results. Thrombus formation was no longer evident at 24 hours (Fig 4C and 4D).…”

Section: Plos Onesupporting

confidence: 87%

“…drug-induced coagulopathy, or coagulopathy occurring as the result of a systemic disorder). Reported risks of TEE are similar for both 4F-PCC and plasma in randomised controlled trials of VKA reversal [ 18 , 36 – 38 ], although real-world evidence from a retrospective patient chart review suggests that TEE risk may be greater for patients receiving 4F-PCC compared with FFP [ 39 ]. Based on retrospective studies and a systematic review, the TEE risk associated with clinical use of 4F-PCC in DOAC-mediated bleeding is low [ 40 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…To date, clinical data available on the safety profile of 4F-PCC in trauma are limited. 4F-PCC is an established clinical treatment for VKA reversal, with TEE risk similar to that of plasma [10,11,18]; data on the thrombotic safety of 4F-PCC in DOAC reversal (which lies outside the licensed indication for 4F-PCC) are more limited [19][20][21][22], although animal studies generally show a good safety profile [19][20][21]. Data from pig models of dilutional coagulopathy have suggested that PCC treatment is associated with improved outcomes (i.e.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models

et al. 2021

View full text Add to dashboard Cite

Objectives Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models. Methods The first model was a modified Wessler model of venous stasis-induced thrombosis in rabbit, focusing on dilutional coagulopathy; the second model employed the same system but focused on direct oral anticoagulant reversal (i.e. edoxaban). The third model assessed the prothrombotic impact of 4F-PCC, aPCC and rFVIIa in a rat model of ferric chloride-induced arterial thrombosis. Results In the first model, thrombi were observed at aPCC doses ≥10 IU/kg (therapeutic dose 100 IU/kg) and rFVIIa doses ≥50 μg/kg (therapeutic dose 90 μg/kg), but not 4F-PCC 50 IU/kg (therapeutic dose 50 IU/kg). The impact of 4F-PCC (up to 300 IU/kg) on thrombus formation was evident from 10 minutes post-administration, but not at 24 hours post-administration; this did not change with addition of tranexamic acid and/or fibrinogen concentrate. 4F-PCC-induced thrombus formation was lower after haemodilution versus non-haemodilution. In the second model, no prothrombotic effect was confirmed at 4F-PCC 50 IU/kg. The third model showed lower incidence of thrombus formation for 4F-PCC 50 IU/kg versus aPCC (50 U/kg) and rFVIIa (90 μg/kg). Conclusions These results suggest that 4F-PCC has a low thrombotic potential versus aPCC or rFVIIa, supporting the clinical use of 4F-PCC for the treatment of coagulopathy-mediated bleeding.

show abstract

Section: Plos Onesupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models

et al. 2021

View full text Add to dashboard Cite

show abstract

“…5 Kcentra ® (CSL Behring GmbH, Marburg, Germany) is currently the only 4F-PCC approved in the US for urgent VKA reversal in patients with major bleeding or who require urgent surgical/invasive procedures. 14 Although the efficacy and safety of 4F-PCCs are well established for VKA reversal, [15][16][17][18][19] there is lack of consensus regarding optimal dosing strategies. 20 On-label dosing of Kcentra is a variable-dose regimen based on bodyweight and pre-treatment INR.…”

Section: Introductionmentioning

confidence: 99%

“…Although the efficacy and safety of 4F-PCCs are well established for VKA reversal, 15 –19 there is lack of consensus regarding optimal dosing strategies. 20 On-label dosing of Kcentra is a variable-dose regimen based on bodyweight and pre-treatment INR.…”

Section: Introductionmentioning

confidence: 99%

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Rhoney

Chester

Darsey

2020

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

Expert consensus and international guidelines recommend urgent co-administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) to rapidly reverse VKA-related bleeding. This narrative review examined real-world evidence and strategies to optimize international normalized ratio (INR) reversal, hemostasis, and outcomes in patients receiving 4F-PCC in this setting. Key determinants for success include the appropriate use of alternative dosing and administration strategies, such as fixed dosing and increased infusion speed, adherence to institutional guidelines, and removing significant institutional barriers to reduce time to treatment. In the opinion of authors, minimizing the time to treatment with 4F-PCCs is of paramount importance when treating patients with VKA-related bleeding. Practices that safely and feasibly shorten the time to administration should be included in guidelines for institutions responsible for anticoagulant care, and adhered to in centers that perform invasive procedures on patients receiving VKA therapy. Further studies are required to optimize use of 4F-PCC, particularly in relation to the ideal dosing strategy and the role of INR.

show abstract

Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis

Mohammadi

Yaribash

Sani

et al. 2021

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

Prothrombin Complex Concentrates are Superior to Fresh Frozen Plasma for Emergency Reversal of Vitamin K Antagonists: A Meta-Analysis in 2606 Subjects

Cited by 12 publications

References 39 publications

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About