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Record W4408959981 · doi:10.1001/jama.2025.3501

Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery

2025· letter· en· W4408959981 on OpenAlexafffundabout
Keyvan Karkouti, Jeannie Callum, Justyna Bartoszko, Kenichi A. Tanaka, Sigurd Knaub, Sukhpal Brar, Kamrouz Ghadimi, Antoine Rochon, Darren Mullane, Étienne J. Couture, Yulia Lin, Christopher Harle, Michelle P. Zeller, Diem Tran, Cristina Solomon, Vivek Rao, Michael R. Law, Amir L. Butt, Edward P. Chen, Maria Rosal Martins, Tarit Saha, Andrew W. Shih, Marie-Claude Vézina, Fuad Moussa, Raffael Pereira Cezar Zamper, Summer Syed, Hakan Buyukdere, Sylvia Werner, Deep Grewal, Daniel Wong, Kofi Vandyck, Robert Tanzola, Bevan Hughes, Olivier Royer, Sophia Wong, Jerrold H. Levy, Roger Lewis, Frank W. Sellke, Melissa M. Cushing, Jennifer Kowalski, Sara Asmail, Shamashtika Thilagaratnam, Paril Suthar, Mary Azenabor, Joseph Cyr, Oksana Kucheryava, Stephanie Pascaru, Miki Peer, Lusine Abrahamyan, Blaine Achen, Matthew Coley, Philippe Demers, Dana V. Devine, Alana M. Flexman, Hilary P. Grocott, Yoan Lamarche, Camila Machado de Souza, C. David Mazer, Katerina Pavenski, Darrin Payne, Mark J. Peterson, Fraser D. Rubens, Damon C. Scales, Terri Sun, Alan Tinmouth, George Tomlinson, Michelle Wong, Stuart A. McCluskey, Lani Lieberman, Jo Carroll, Shahrzad Firouzian, Nishanthi Liyanage, Humara Poonawala, r. Md. Shamimul Kabir, Alioska Escorcia, Michelle Mozel, Ramanjot Kaur, Rebecca Randall, Kelly Bizovie, Sarah Buchko, Sunny Khakh, Jenna Van Roekel, Raunika Lertnamvongwan, Hisako Okada, Deborah DuMerton, Reegan Tod, Bethany Smethurst, Aiden Scholey, Angela Sirosky-Yanyk, Andrew Stevens, Ester Cisneros-Aguilera, Alexandre Bergeron, Sakara Hutspardol, Shirley Geok‐lin Lim, Mi Jian, Debbie Kalar, Erick Lorenzana-Saldivar, Akash Gupta, Angela Jerath, Pablo Pérez d’Empaire, Chantal Armali, Lilia Kaustov, A. Malkin, Connie Colavecchia, Harley Meirovich, Jane Yang, François Laforge, Nathalie Gagné, Marie Soleil Saillant, Éric Dumont, Marie-Ève Charest, Mackenzie Quantz, Robert C. Mayer, Jeff Kinney, Lee-Anne Fochesato, Yuxin Bai, Iqbal Jaffar, Nour Alhomsi, Jay Guevarra, Erin Jamula, Melanie Tokessy, Elizabeth Watt, Hadia Arabi Katbi, Amy Moorehead, Gianluigi Bisleri

Bibliographic record

VenueJAMA · 2025
Typeletter
Languageen
FieldMedicine
TopicTrauma, Hemostasis, Coagulopathy, Resuscitation
Canadian institutionsHamilton Health SciencesOakville-Trafalgar Memorial HospitalLondon Health Sciences CentreCanadian Blood ServicesSunnybrook Health Science CentreUniversité LavalVancouver General HospitalRoyal Columbian HospitalUniversité de MontréalUniversity of British ColumbiaMontreal Heart InstituteQueen's UniversitySunnybrook HospitalUniversity of OttawaKingston Health Sciences CentreHealth Sciences CentreUniversity Health NetworkWestern UniversityUniversity of TorontoMcMaster UniversityToronto General HospitalHamilton General HospitalWomen's College Hospital
FundersCanadian Institutes of Health Research
KeywordsMedicineProthrombin complex concentrateFresh frozen plasmaPROTHROMBIN COMPLEXCardiac surgeryAnesthesiaSurgeryCardiologyInternal medicinePlateletCoagulationWarfarin

Abstract

fetched live from OpenAlex

Importance: Excessive bleeding is a common and prognostically important complication of cardiac surgery. For bleeding related to coagulation factor deficiency, frozen plasma is the most used therapy. Preliminary trials indicate that 4-factor prothrombin complex concentrate (PCC) may be a suitable alternative. Objective: To compare the efficacy and safety of PCC with frozen plasma in patients undergoing cardiac surgery with coagulopathic bleeding. Design, Setting, and Participants: Unblinded randomized noninferiority controlled clinical trial at 12 hospitals in Canada and the US involving adults (≥18 years) who had developed bleeding related to coagulation factor deficiency after termination of cardiopulmonary bypass during surgery (November 30, 2022, to May 28, 2024). Final 30-day follow-up visit was completed on June 28, 2024. Intervention: A total of 265 patients were randomized to receive PCC (1500 IU ≤60 kg; 2000 IU >60 kg) and 263, frozen plasma (3 U ≤60 kg; 4 U >60 kg) in the operating room. A second dose was allowed over the next 24 hours if indicated; thereafter, only frozen plasma could be used. Main Outcomes and Measures: The primary outcome was hemostatic response (effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation). The noninferiority of PCC vs frozen plasma was assessed using a 10% margin and a 1-sided α of .025, with subsequent testing for superiority if noninferiority was demonstrated. Secondary outcomes included allogeneic blood transfusions and adverse events. Patients were followed up until postoperative day 30. Results: Of 538 enrolled patients, 420 patients (median age, 66 years [IQR, 57-73 years]; 74%, male; 10%, Asian; 1%, Black; and 65%, White) were included in the primary analysis; of those, 296 (70%) underwent complex surgeries. Compared with the 207 patients in the frozen plasma group, the 213 patients in the PCC group had higher hemostatic effectiveness (166 [77.9%] vs 125 [60.4%]; difference, 17.6%; 95% CI, 8.7%-26.4%; P < .001 for noninferiority and superiority) and had received fewer transfusions including red blood cells, platelets, and noninvestigational frozen plasma units (mean, 6.6 units; 95% CI, 5.7-7.7 vs 9.3 units; 95% CI, 8.0-10.8; difference, 2.7; 95% CI, 1.0-4.4; P = .002). Seventy-seven patients (36.2%) in the PCC group vs 98 (47.3%) in the frozen plasma group experienced serious adverse events (relative risk [RR], 0.76; 95% CI, 0.61-0.96; P = .02). Twenty-two patients (10.3%) in the PCC group and 39 (18.8%) in the frozen plasma group had acute kidney injury (RR, 0.55; 95% CI, 0.34-0.89; P = .02). Conclusions and Relevance: In this unblinded randomized clinical trial, PCC had superior hemostatic efficacy and safety advantages to frozen plasma among patients requiring coagulation factor replacement for bleeding during cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT05523297.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Commentary · Consensus signal: Commentary
Teacher disagreement score0.159
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.054
GPT teacher head0.302
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreCommentary

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations48
Published2025
Admission routes3
Has abstractyes

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Same venueJAMASame topicTrauma, Hemostasis, Coagulopathy, ResuscitationFrench-language works237,207