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. 2022 Nov 21;11(11):CD013551.
doi: 10.1002/14651858.CD013551.pub2.

Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding

Affiliations

Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding

Katia Hayes et al. Cochrane Database Syst Rev. .

Abstract

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Organisation (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/), for ongoing or unpublished trials.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. AUTHORS' CONCLUSIONS: PCCs could potentially be used as an alternative to standard therapy for coagulopathic bleeding post-cardiac surgery compared to FFP as shown by moderate-quality evidence and it may be an alternative to rFVIIa in refractory non-surgical bleeding but this is based on moderate to very low quality of evidence.

Trial registration: ClinicalTrials.gov NCT03715348 NCT04114643 NCT02557672 NCT04244981 NCT04434001.

PubMed Disclaimer

Conflict of interest statement

KH ‐ none known.

MF ‐ none known.

VJ ‐ none known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph for RCT studies: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary for RCT studies: review authors' judgements about each risk of bias item for each included study
4
4
NRS: Blood products transfused (RBC) % of patients
5
5
NRS: PCCs thrombotic events
6
6
NRS: PCCs mortality
7
7
NRS: PCCs ICU length of stay
8
8
NRS: PCCs renal replacement therapy
9
9
NRS: PCCS ventilator duration
10
10
NRS: Factor VIIa blood products transfused (RBC) % patients
11
11
NRS: Factor VIIa thrombotic events
12
12
NRS: Factor VIIa mortality
13
13
NRS: Factor VIIa ICU length of stay
14
14
NRS: Factor VIIa renal replacement therapy
1.1
1.1. Analysis
Comparison 1: PCC versus standard treatment, Outcome 1: RCT: Blood products transfused (RBC) in units
1.2
1.2. Analysis
Comparison 1: PCC versus standard treatment, Outcome 2: NRS: Blood products transfused (RBC) in units
1.3
1.3. Analysis
Comparison 1: PCC versus standard treatment, Outcome 3: RCT: Blood products transfused (RBC) % of patients
1.4
1.4. Analysis
Comparison 1: PCC versus standard treatment, Outcome 4: NRS: Blood products transfused (RBC) % of patients
1.5
1.5. Analysis
Comparison 1: PCC versus standard treatment, Outcome 5: RCT: Thrombotic events
1.6
1.6. Analysis
Comparison 1: PCC versus standard treatment, Outcome 6: NRS: Thrombotic events
1.7
1.7. Analysis
Comparison 1: PCC versus standard treatment, Outcome 7: NRS: Thrombotic events matched data
1.8
1.8. Analysis
Comparison 1: PCC versus standard treatment, Outcome 8: NRS: Thrombotic events (3‐factor vs 4‐factor)
1.9
1.9. Analysis
Comparison 1: PCC versus standard treatment, Outcome 9: RCT: Mortality (30‐day)
1.10
1.10. Analysis
Comparison 1: PCC versus standard treatment, Outcome 10: NRS: Mortality (30‐day)
1.11
1.11. Analysis
Comparison 1: PCC versus standard treatment, Outcome 11: NRS: Mortality (30‐day)
1.12
1.12. Analysis
Comparison 1: PCC versus standard treatment, Outcome 12: RCT: Bleeding (chest drain output) in mLs for the first 12 hours
1.13
1.13. Analysis
Comparison 1: PCC versus standard treatment, Outcome 13: RCT: Intensive care length of stay in hours
1.14
1.14. Analysis
Comparison 1: PCC versus standard treatment, Outcome 14: NRS: Intensive care length of stay in hours
1.15
1.15. Analysis
Comparison 1: PCC versus standard treatment, Outcome 15: RCT: Incidence of renal replacement therapy
1.16
1.16. Analysis
Comparison 1: PCC versus standard treatment, Outcome 16: NRS: Incidence of renal replacement therapy
1.17
1.17. Analysis
Comparison 1: PCC versus standard treatment, Outcome 17: RCT: Ventilator hours
1.18
1.18. Analysis
Comparison 1: PCC versus standard treatment, Outcome 18: NRS: Ventilator hours
2.1
2.1. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 1: Blood products transfused (RBC) in units
2.2
2.2. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 2: Blood products transfused (RBC) % of patients
2.3
2.3. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 3: Thrombotic events
2.4
2.4. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 4: Mortality (30‐day)
2.5
2.5. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 5: Bleeding (chest drain output) in mLs for the first 12 hours
2.6
2.6. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 6: Intensive care length of stay in hours
2.7
2.7. Analysis
Comparison 2: PCC versus rFVIIa, Outcome 7: Incidence of renal replacement therapy

Update of

  • doi: 10.1002/14651858.CD013551

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References to ongoing studies

NCT02557672 {unpublished data only}
    1. NCT02557672. PCC vs. FFP for post cardiopulmonary bypass coagulopathy and bleeding. clinicaltrials.gov/show/NCT02557672 (first received 23 September 2015).
NCT04244981 {unpublished data only}
    1. NCT04244981. Efficacy of prothrombin complex concentrate reducing perioperative blood loss in cardiac surgery. clinicaltrials.gov/show/NCT04244981 (first received 28 January 2020).
NCT04434001 {published data only}
    1. NCT04434001. ZEPLAST- PED: zEro_PLASma trial in small infants undergoing cardiac surgery. protect-au.mimecast.com/s/Uq9fCyoj4JiL8JwysR34FhX?domain=clinicaltrials.gov (first received 16 June 2020).

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