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Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery.

ABSTRACT: Bleeding after cardiac surgery requiring surgical reexploration and blood component transfusion is associated with increased morbidity and mortality. Although prothrombin complex concentrate (PCC) has been used satisfactorily in bleeding disorders, studies on its efficacy and safety after cardiopulmonary bypass are limited.Between January 2005 and December 2013, 3454 consecutive cardiac surgery patients were included in an observational study aimed at investigating the efficacy and safety of PCC as first-line coagulopathy treatment as a replacement for fresh frozen plasma (FFP). Starting in January 2012, PCC was introduced as solely first-line treatment for bleeding following cardiac surgery.After one-to-one propensity score-matched analysis, 225 pairs of patients receiving PCC (median dose 1500 IU) and FFP (median dose 2 U) were included. The use of PCC was associated with significantly decreased 24-h post-operative blood loss (836 ± 1226 vs. 935 ± 583 ml, p < 0.0001). Propensity score-adjusted multivariate analysis showed that PCC was associated with significantly lower risk of red blood cell (RBC) transfusions (odds ratio [OR] 0.50; 95% confidence interval [CI] 0.31-0.80), decreased amount of RBC units (β unstandardised coefficient -1.42, 95% CI -2.06 to -0.77) and decreased risk of transfusion of more than 2 RBC units (OR 0.53, 95% CI 0.38-0.73). Patients receiving PCC had an increased risk of post-operative acute kidney injury (AKI) (OR 1.44, 95% CI 1.02-2.05) and renal replacement therapy (OR 3.35, 95% CI 1.13-9.90). Hospital mortality was unaffected by PCC (OR 1.51, 95% CI 0.84-2.72).In the cardiac surgery setting, the use of PCC compared with FFP was associated with decreased post-operative blood loss and RBC transfusion requirements. However, PCC administration may be associated with a higher risk of post-operative AKI.

SUBMITTER: Cappabianca G

PROVIDER: S-EPMC4702344 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:BackgroundPatients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal.Methods and resultsIn this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, -5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event.Conclusions4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00708435.

Project description:ImportanceApproximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative.ObjectivesTo determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures.Design, setting, and participantsParallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020.InterventionsProthrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation.Main outcomes and measuresHemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery.ResultsOf 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar.Conclusions and relevanceThis randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery.Trial registrationClinicalTrials.gov Identifier: NCT04114643.

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Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery.

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