Fresh frozen plasma for patients undergoing surgery on the heart or blood vessels

Fresh frozen plasma is obtained from whole blood from blood donors. It contains a number of factors that help blood to clot. The risk of bleeding in open heart surgery or surgery on the main blood vessels in the body is high. Fresh frozen plasma is sometimes administered to these patients to reduce bleeding. It can be administered prophylactically (to prevent bleeding) or therapeutically (to treat bleeding). However, there are risks of side effects from fresh frozen plasma, such as severe allergic reactions or breathing problems.

We searched scientific sources to identify eligible trials and found 15 studies with 755 patients. The evidence is up to date to April 2015. Fourteen studies compared prophylactic FFP against no FFP and one study compared two types of FFP, both used therapeutically. No studies reported on all outcomes. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.

Our primary outcome was death within 30 days after surgery. Six trials (with 287 patients) looked at this outcome and found no clear difference in mortality between the treatment arms but the quality of the evidence was very low. There was also no difference in the amount of blood lost in the first 24 hours following surgery (measured in five trials; low quality evidence), or the risk of returning to theatre for a reoperation (measured in eight trials; moderate quality evidence). Patients who had FFP received significantly more red blood cells, suggesting that FFP may not be effective in this setting (moderate quality evidence). Measurement of a blood test used to assess blood clotting (prothrombin time) was reported in eight trials and showed that clotting was improved by the use of prophylactic FFP (moderate quality evidence). However, the difference was too small to make a difference in clinical practice. Only one included study reported adverse events as an outcome and reported no adverse events due to FFP transfusion.

The review found no evidence for the efficacy of FFP for the prevention of bleeding in heart surgery and it found some evidence of an increased overall need for red cell transfusion in those treated with FFP. There were no reported adverse events due to FFP transfusion. Overall the evidence for the safety and efficacy of prophylactic FFP for cardiac surgery is insufficient. The trials focused on prevention of bleeding and did not address prevention of bleeding for patients with abnormal blood clotting or for the treatment of bleeding patients.

Authors' conclusions: 

This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of patients with coagulopathies or those who are undergoing emergency surgery. There were no reported adverse events attributable to FFP transfusion, although there was a significant increase in the number of patients requiring red cell transfusion who were randomised to FFP. Variability in outcome reporting between trials precluded meta-analysis for many outcomes across all trials, and there was evidence of a high risk of bias in most of the studies. Further adequately powered studies of FFP, or comparable pro-haemostatic agents, are required to assess whether larger reductions in prothrombin time translate into clinical benefits. Overall the evidence from randomised controlled trials for the safety and efficacy of prophylactic transfusion of FFP for cardiac surgery is insufficient.

Read the full abstract...
Background: 

Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP.

Objectives: 

To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding.

Search strategy: 

We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status.

Selection criteria: 

We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange.

Data collection and analysis: 

Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial.

Main results: 

We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.

Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.

There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).

Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion.