Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery

Karkouti, Keyvan; Bartoszko, Justyna; Grewal, Deep; Bingley, Cielo; Armali, Chantal; Carroll, Jo; Hucke, Hans-Peter; Kron, Amie; McCluskey, Stuart A.; Rao, Vivek; Callum, Jeannie

doi:10.1001/jamanetworkopen.2021.3936

Cited by 40 publications

(36 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Karkouti et al 27 Patients receiving PCC following cardiac surgery required fewer blood products than those resuscitated with FFP for coagulopathy.…”

Section: Hemostasismentioning

confidence: 99%

Year in Review 2021: Noteworthy Literature in Cardiothoracic Critical Care

Weitzel

2022

Semin Cardiothorac Vasc Anesth

View full text Add to dashboard Cite

This year marked a number of milestones in critical care. As vaccines for the SARS-CoV-2 virus became widely available and were confirmed to be exceptionally effective against severe illness and hospitalization, we were then faced with new variants and the resource-intense responses necessary to combat them. Despite challenges new and old, we have persevered and continued to provide excellent care to our patients while pushing the boundaries of clinical research. This article is a collection of studies published in 2021 relevant to critical care, with a specific focus on cardiothoracic critical care. To ignore the impact of the COVID-19 pandemic would do a disservice to our colleagues, many of whom have made incredible breakthroughs in novel therapies to the coronavirus, and yet we present additional themes of delirium, acute kidney injury, lung transplant, advances in ECMO as well as biomarkers of sepsis.

show abstract

“…Karkouti et al 27 Patients receiving PCC following cardiac surgery required fewer blood products than those resuscitated with FFP for coagulopathy.…”

Section: Hemostasismentioning

confidence: 99%

Year in Review 2021: Noteworthy Literature in Cardiothoracic Critical Care

Weitzel

2022

Semin Cardiothorac Vasc Anesth

View full text Add to dashboard Cite

show abstract

“…28 The variability in practice pertaining to administration of PCC vs FP should be explored further, and extends to the doses utilized by clinicians. Currently there is no clear consensus on the optimal dose of PCC for coagulopathy related to cardiac surgery, 17 , 29 , 30 with doses in our study ranging from 500 to 2,000 IU for a single administration. Given the significant differences in transfusion avoidance in favour of the PCC group in this study, our results suggest a dose between 1,000 IU and 2,000 IU is likely to be effective.…”

Section: Discussionmentioning

confidence: 94%

“…doses of 15-25 IUÁkg -1 (1,000-2,000 IU for an average sized patient), with observed hemostatic effects comparable with FP observed throughout this dose range, albeit in small numbers of patients. 29,30 This study builds on existing evidence and re-examines the efficacy of PCCs, while adding to the sparse published data on the safety of PCCs in the context of bleeding after cardiac surgery. Previously published work has been limited by small sample sizes, making comparisons of rare outcomes between groups difficult because of insufficient power.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The association of prothrombin complex concentrates with postoperative outcomes in cardiac surgery: an observational substudy of the FIBRES randomized controlled trial

Bartoszko

Callum

Karkouti

2021

Can J Anesth/J Can Anesth

Self Cite

View full text Add to dashboard Cite

Purpose The mainstay of therapy for coagulation factor deficiency in cardiac surgical patients is frozen plasma (FP); however, prothrombin complex concentrates (PCCs) may offer logistical and safety advantages. As there is limited comparative evidence, we conducted this study to explore the association of comparable PCC or FP doses with transfusion and outcomes. Methods This was a post hoc analysis of a multicentre randomized trial comparing fibrinogen concentrate with cryoprecipitate (FIBRES trial) in bleeding cardiac surgical patients. This analysis included 415 patients who received only PCC (n = 72; 17%) or only FP (n = 343; 83%) for factor replacement. The main outcomes of interest were red blood cell (RBC) and platelet transfusion within 24 hr of cardiopulmonary bypass. Secondary outcomes included postoperative adverse events. Associations were examined by hierarchical generalized estimating equation models adjusted for demographic and surgical characteristics. ResultsThe median [interquartile range (IQR)] PCC dose was 1,000 [1,000-2,000] units, while the median [IQR] FP dose was 4 [2-6] units. Each unit of FP was independently associated with increased adjusted odds of RBC (1.60; 95% confidence interval [CI], 1.36 to 1.87; P\0.01) and platelet transfusion (1.40; 95% CI, 1.15 to 1.69; P\0.01) while each 500 units of PCC was independently associated with reduced adjusted odds of RBC (0.67; 95% CI, 0.50 to 0.90; P\0.01) and platelet transfusion (0.80; 95% CI, 0.70 to 0.92; P \ 0.01). Adverse event rates were comparable.

show abstract

“…Most recently, Karkouti et al described a pilot RCT comparing 4F-PCC to fresh frozen plasma in 101 patients undergoing cardiac surgery who developed difficult-to-manage bleeding following CPB. 15 Comparing 4F-PCC to fresh frozen plasma rather than placebo in bleeding patients is an ethical study design that allows for comparison between two reasonable management approaches. In addition to clinical data, the group also collected laboratory data at different points which, at best, allowed for assessment of confounders, and at the very least could provide hypothesis-generating clues about the efficacy of the study drugs.…”

mentioning

confidence: 99%

Out of Control: Why Randomized Trials of Factor Concentrates Are So Elusive

Thalji

Patel

2021

Journal of Cardiothoracic and Vascular Anesthesia

View full text Add to dashboard Cite

Bleeding in the perioperative and postoperative periods continues to be a major concern in cardiac surgery. 1 Although, in most cases, the combination of blood product transfusion, antifibrinolytic therapy, improved surgical hemostasis, and time are sufficient to achieve hemostasis, this is not always adequate. The reasons for variability in perioperative hemostasis are not known, although certain patient and surgical characteristics, including prior history of cardiac surgery, underlying bleeding diathesis, emergent surgery, and cardiopulmonary bypass (CPB) duration, have been associated with increased peri-and postoperative bleeding. 1,2 Despite often uncertain causes of persistent perioperative bleeding, even with usual resuscitative efforts, practitioners frequently turn to purified coagulation factor concentrates to enhance hemostasis. These include three-or four-factor prothrombin complex concentrates (3F-PCC or 4F-PCC), 3,4 recombinant activated factor VII (rVIIa) (NovoSeven), 4,5 and, as described by O'Donnell et al. in this issue of the Journal of Cardiothoracic and Vascular Anesthesia, activated prothrombin complex concentrates, 6 also known as factor 8 inhibitor bypassing agent (FEIBA). Although 4F-PCC sometimes is used in cardiac surgery for its approved indication of warfarin reversal, the use of purified factor concentrates is, in general, off-label, in large part due to the lack of data supporting their efficacy and safety in this patient population.

show abstract

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery

Cited by 40 publications

References 29 publications

Year in Review 2021: Noteworthy Literature in Cardiothoracic Critical Care

Year in Review 2021: Noteworthy Literature in Cardiothoracic Critical Care

The association of prothrombin complex concentrates with postoperative outcomes in cardiac surgery: an observational substudy of the FIBRES randomized controlled trial

Out of Control: Why Randomized Trials of Factor Concentrates Are So Elusive

Contact Info

Product

Resources

About