Four-factor prothrombin complex concentrates (PCCs) were found during a parallel-group randomized clinical trial to be a suitable alternative to frozen plasma (FP) for managing bleeding in patients undergoing cardiac surgery. The results of this study (ClinicalTrials.gov Identifier: NCT04114643) were published in JAMA Network Open.

From 2019 to 2020, patients undergoing cardiac surgery who required coagulation factor replacement at 2 centers in Canada were randomized to receive 1500 IU to 2000 IU PCC (n=54) or 3 U to 4 U FP (n=47) within 48 hours before surgery. Treatment response, need for allogeneic blood components, and red cell transfusions were assessed.

Patients were median age 64 years (interquartile range [IQR], 54-73); 28% were women, and 81% underwent complex cardiac operations. Recipients of PCC were given a median of 24.9 IU/kg (IQR, 21.8-27.0) and those receiving FP were given a median of 12.5 mL/kg (IQR, 10.0-15.0).


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Among the PCC cohort, 5 patients required a second PCC dose, and 2 required 1 or 2 doses of FP. For the FP cohort, a second dose of FP was administered to 9 patients.

At 4 hours, 80% of the PCC cohort and 68% of the FP cohort (P =.25) did not require hemostatic therapy, and neither did 76% and 66% (P =.28) at 24 hours among the PCC and FP cohorts, respectively. The PCC group received 42% (95% CI, 23%-55%; P <.001) lower mean ratio of cumulative allogeneic blood components, specifically 94% (95% CI, 89%-97%; P <.001) less FP and 31% (95% CI, 1%-53%; P =.05) less red cell transfusions at 24 hours.

Lower chest tube drainage was associated with PCC treatment at both 12 hours (median, 310 vs 500 mL; P <.001) and 24 hours (median, 450 vs 700 mL; P <.001).

Rates of all adverse events were lower among the PCC (77.8%) recipients compared with FP (87.2%); however, more patients receiving PCC had serious adverse events (35.2% vs 28.6%). In each group, 4 patients had thromboembolic events and 2 died.

This study may have been limited by the fact that no standard transfusion protocol was enforced, as this study was conducted during the course of usual care.

The study data indicated PCC may be a viable treatment alternative to FP in patients undergoing cardiac surgery, and a large adequately powered multicenter trial of PCC is warranted.

Disclosure: This clinical trial was supported in part by Octapharma AG (Lachen, Switzerland). Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Karkouti K, Bartoszko J, Grewal D, et al. Comparison of 4-factor prothrombin complex concentrate with frozen plasma for management of hemorrhage during and after cardiac surgery: a randomized pilot trial. JAMA Netw Open. Published online April 1, 2021. 2021;4(4):e213936. doi:10.1001/jamanetworkopen.2021.3936