Background

Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post‐cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation.  

Objectives

Assess the benefits and harms of PCCs in people undergoing cardiac surgery who have coagulopathic non‐surgical bleeding.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase and Conference Proceedings Citation Index‐Science (CPCI‐S) on the Web of Science on 20 April 2021. We searched Clinicaltrials.gov (www.clinicaltrials.gov), and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/), for ongoing or unpublished trials. We checked the reference lists for additional references. We did not limit the searches by language or publication status.

Selection criteria

We included randomised controlled trials (RCTs) and non‐randomised trials (NRSs). 

Data collection and analysis

We used standard methodological procedures expected by Cochrane.  

Main results

Eighteen studies were included  (4993 participants). Two were RCTs (151 participants) and 16 were NRSs. Both RCTs had low risk of bias (RoB) in almost all domains. Of the 16 NRSs, 14 were retrospective cohort analyses with one prospective study and one case report. The nine studies used in quantitative analysis were judged to have critical RoB, three serious and three moderate.  

1. PCC versus standard treatment

Evidence from RCTs showed PCCs are likely to reduce the number of units transfused compared to standard care (MD ‐0.89, 95% CI ‐1.78 to 0.00; participants = 151; studies = 2; moderate‐quality evidence). Evidence from NRSs agreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (MD ‐1.87 units, 95% CI ‐2.53 to ‐1.20; participants = 551; studies = 2; very low‐quality evidence).

There was no evidence from RCTs showing a difference in the incidence of red blood cell (RBC) transfusion compared to standard care (OR 0.53, 95% CI 0.20 to 1.40; participants = 101; studies = 1; low‐quality evidence). Evidence from NRSs disagreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (OR 0.54, 95% CI 0.30 to 0.98; participants = 1046; studies = 4; low‐quality evidence).

There was no evidence from RCTs showing a difference in the number of thrombotic events with PCC compared to standard care (OR 0.68 95% CI 0.20 to 2.31; participants = 152; studies = 2; moderate‐quality evidence). This is supported by NRSs, showing that PCCs may have no effect on the number of thrombotic events compared to standard care but the evidence is very uncertain (OR 1.32, 95% CI 0.87 to 1.99; participants = 1359; studies = 7; very low‐quality evidence).

There was no evidence from RCTs showing a difference in mortality with PCC compared to standard care  (OR 0.53, 95% CI 0.12 to 2.35; participants = 149; studies = 2; moderate‐quality evidence). This is supported by evidence from NRSs, showing that PCCs may have little to no effect on mortality compared to standard care but the evidence is very uncertain (OR 1.02, 95% CI 0.69 to 1.51; participants = 1334; studies = 6; very low‐quality evidence).

Evidence from RCTs indicated that there was little to no difference in postoperative bleeding (MD ‐107.05 mLs, 95% CI ‐278.92 to 64.83; participants = 151, studies = 2; low‐quality evidence). 

PCCs may have little to no effect on intensive care length of stay (RCT evidence: MD ‐0.35 hours, 95% CI ‐19.26 to 18.57; participants = 151; studies = 2; moderate‐quality evidence) (NRS evidence: MD ‐18.00, 95% CI ‐43.14 to 7.14; participants = 225; studies = 1; very low‐quality evidence) or incidence of renal replacement therapy (RCT evidence: OR 0.72, 95% CI 0.14 to 3.59; participants = 50; studies = 1; low‐quality evidence) (NRS evidence: OR 1.46, 95% CI 0.71 to 2.98; participants = 684; studies = 2; very low‐quality evidence).

No studies reported on additional adverse outcomes.  

2. PCC versus rFVIIa

For this comparison, all evidence was provided from NRSs. 

PCC likely results in a large reduction of RBCs transfused intra‐operatively in comparison to rFVIIa (MD‐4.98 units, 95% CI ‐6.37 to ‐3.59; participants = 256; studies = 2; moderate‐quality evidence). 

PCC may have little to no effect on the incidence of RBC units transfused comparative to rFVIIa; evidence is very uncertain (OR 0.16, 95% CI 0.02 to 1.56; participants = 150; studies = 1; very low‐quality evidence).

PCC may have little to no effect on the number of thrombotic events comparative to rFVIIa; evidence is very uncertain (OR 0.51, 95% CI 0.23 to 1.16; participants = 407; studies = 4; very low‐quality evidence).

PCC may have little to no effect on the incidence of mortality (OR 1.07, 95% CI 0.38 to 3.03; participants = 278; studies = 3; very low‐quality evidence) or intensive care length of stay comparative to rFVIIa (MD ‐40 hours, 95% CI ‐110.41 to 30.41; participants = 106; studies = 1; very low‐quality evidence); evidence is very uncertain .

PCC may reduce bleeding (MD ‐674.34 mLs, 95% CI ‐906.04 to ‐442.64; participants = 150; studies = 1; very low‐quality evidence) and incidence of renal replacement therapy (OR 0.29, 95% CI 0.12 to 0.71; participants = 106; studies = 1; very low‐quality evidence) comparative to rFVIIa; evidence is very uncertain.

No studies reported on other adverse events.