NIHR Signal Cell salvage during caesarean section doesn’t reduce blood transfusions

Published on 15 May 2018

In a large UK trial, cell salvage for women at risk of blood loss during caesarean did not reduce the need for donor blood transfusion, though few needed transfusion (2.5% compared with 3.5% among controls).

More babies are being born by caesarean section and if blood loss is excessive, transfusions may be required, probably by about one in 20 women. Collecting the mother’s own lost blood during the procedure, filtering and returning it to her (cell salvage) is a potential alternative that could reduce the need for donated blood.

This NIHR-funded trial included around 3,000 women in 26 obstetric units in the UK. It sought to see if cell salvage reduced transfusions for women undergoing elective or emergency caesarean, and thought to be at increased risk of haemorrhage (over 5%).  

The findings suggest that cell salvage doesn’t have a routine place in obstetric care.

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Why was this study needed?

NHS maternity data showed that 27.8% of all deliveries in England (2016/17) were by caesarean section, and it is increasing.

Excessive blood loss during caesarean section is a cause of maternal death and other complications such as emergency hysterectomy. Potentially life-threatening haemorrhage or subsequent severe anaemia is usually replaced via donor blood transfusion, thought to be needed in about 5% of caesarean deliveries. But the finite amount of donor blood and risks, such as transfusion reaction, require a search for alternatives.

Cell salvage is one potential option, but its safety and effectiveness in maternity care are based on two small trials with inconclusive findings.

This large randomised controlled trial aimed to determine whether routine use of cell salvage during caesarean for high-risk women could reduce the need for donor blood transfusion.

What did this study do?

The SALVO trial included 3,028 women from 26 UK obstetric units who needed emergency caesarean or were having elective caesarean for reasons other than choice or breech delivery. Breech delivery was excluded as they are known to be at increased risk of haemorrhage.

Women were randomised to usual care or to cell salvage, where blood lost during caesarean was routinely collected, processed and returned to the mother. Randomisation was balanced according to reason for caesarean, condition of the placenta and whether it was single or multiple births.

Rate of donor blood transfusion was the main outcome. They also looked at how many Rhesus (RhD) negative mothers were exposed to greater than 2ml of RhD-positive fetal blood (feto-maternal haemorrhage).

The sample size was sufficient to detect small differences in transfusion rates between groups. In a life-threatening emergency, women were managed in line with hospital protocol, which could include cell salvage in the control group.

What did it find?

  • Of 1,498 women assigned to the intervention group, 95.6% had cell salvage machinery set up while 50.8% had salvaged blood returned, an average of 260ml. This compared with cell salvage collection being set up in for 3.9% of 1,492 controls.
  • The donor blood transfusion rate was 2.5% in the intervention group versus 3.5% in the control group, which was not a statistically significant reduction (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01).
  • Cell salvage made no difference to transfusion rates when analysing women who received an elective caesarean (1.8% vs 2.2%, OR 0.83, 95% CI 0.38 to 1.83). The reduction for emergency caesarean was borderline (3.0% vs 4.6%, OR 0.58, 95% CI 0.34 to 0.99).
  • Of 270 RhD-negative mothers carrying RhD-positive babies, 21 women in the cell salvage group (25.6%) experienced feto-maternal haemorrhage compared with nine in the control group (10.5%) (OR 5.63, 95% CI 1.43 to 22.14). The small numbers highlight need for caution with this result. There was no difference in other safety outcomes for all women.

What does current guidance say on this issue?

NICE guidance from 2005 stated that cell salvage is an efficacious blood replacement technique that is well established in other areas of medicine such as cardiac and orthopaedic surgery, but there are safety concerns for its use in obstetric practice. Highlighted risks included fetal cells infusing into the maternal circulation and potentially causing haemolytic disease (the baby’s blood cells being destroyed) in a future pregnancy.

NICE advised it’s only performed by experienced professionals and women informed of complication risk.

The Royal College of Obstetricians and Gynaecologists (2016) advised that emergency use of cell salvage is considered for women with postpartum haemorrhage after caesarean.  

What are the implications?

The findings suggest there isn’t a case for the routine set-up of cell salvage for women undergoing caesarean. That’s not to say it doesn’t still have a role in the emergency management of haemorrhage or very high-risk circumstances when resources and expertise are available.   

The trial was conducted 2013-16 and practice is evolving. Other options to manage maternal haemorrhage are: giving blood fluid (plasma) infused with clotting factors or giving tranexamic acid which prevents blood clots from breaking down.

The finding that cell salvage was associated with a small increase in the chance of RhD-negative mothers being exposed to RhD-positive fetal blood highlights a need for long-term vigilance and perhaps further study.

Citation and Funding

Khan SK, Moore PAS, Wilson MJ, et al. Cell salvage and donor blood transfusion during caesarean section: A pragmatic multicentre randomised controlled trial (SALVO). PLoS Med. 2017;14(12):e1002471.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 10/57/32).

Khan KS, Moore P, Wilson M, et al. A randomised controlled trial and economic evaluation of intraoperative cell salvage during caesarean section in women at risk of haemorrhage: the SALVO (cell SALVage in Obstetrics) trial. Health Technol Assess. 2018;22(2):1-88.

Bibliography

NHS Digital. NHS Maternity Statistics, England 2016-17. Leeds: NHS Digital; 2017.

NICE. Intraoperative blood cell salvage in obstetrics. IPG144. London. National Institute for Health and Clinical Excellence; 2005.

Mavrides E, Allard S, Chandraharan E, et al on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG 2016;124:e106-49.

JPAC. UK Cell Salvage Action Group. London. Joint United Kingdom Blood Transfusion and Tissue Transplantation services Professional Advisory Committee.

The Lancet. Woman: reducing maternal deaths with tranexamic acid. 2017;389(10084):2081.

Why was this study needed?

NHS maternity data showed that 27.8% of all deliveries in England (2016/17) were by caesarean section, and it is increasing.

Excessive blood loss during caesarean section is a cause of maternal death and other complications such as emergency hysterectomy. Potentially life-threatening haemorrhage or subsequent severe anaemia is usually replaced via donor blood transfusion, thought to be needed in about 5% of caesarean deliveries. But the finite amount of donor blood and risks, such as transfusion reaction, require a search for alternatives.

Cell salvage is one potential option, but its safety and effectiveness in maternity care are based on two small trials with inconclusive findings.

This large randomised controlled trial aimed to determine whether routine use of cell salvage during caesarean for high-risk women could reduce the need for donor blood transfusion.

What did this study do?

The SALVO trial included 3,028 women from 26 UK obstetric units who needed emergency caesarean or were having elective caesarean for reasons other than choice or breech delivery. Breech delivery was excluded as they are known to be at increased risk of haemorrhage.

Women were randomised to usual care or to cell salvage, where blood lost during caesarean was routinely collected, processed and returned to the mother. Randomisation was balanced according to reason for caesarean, condition of the placenta and whether it was single or multiple births.

Rate of donor blood transfusion was the main outcome. They also looked at how many Rhesus (RhD) negative mothers were exposed to greater than 2ml of RhD-positive fetal blood (feto-maternal haemorrhage).

The sample size was sufficient to detect small differences in transfusion rates between groups. In a life-threatening emergency, women were managed in line with hospital protocol, which could include cell salvage in the control group.

What did it find?

  • Of 1,498 women assigned to the intervention group, 95.6% had cell salvage machinery set up while 50.8% had salvaged blood returned, an average of 260ml. This compared with cell salvage collection being set up in for 3.9% of 1,492 controls.
  • The donor blood transfusion rate was 2.5% in the intervention group versus 3.5% in the control group, which was not a statistically significant reduction (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01).
  • Cell salvage made no difference to transfusion rates when analysing women who received an elective caesarean (1.8% vs 2.2%, OR 0.83, 95% CI 0.38 to 1.83). The reduction for emergency caesarean was borderline (3.0% vs 4.6%, OR 0.58, 95% CI 0.34 to 0.99).
  • Of 270 RhD-negative mothers carrying RhD-positive babies, 21 women in the cell salvage group (25.6%) experienced feto-maternal haemorrhage compared with nine in the control group (10.5%) (OR 5.63, 95% CI 1.43 to 22.14). The small numbers highlight need for caution with this result. There was no difference in other safety outcomes for all women.

What does current guidance say on this issue?

NICE guidance from 2005 stated that cell salvage is an efficacious blood replacement technique that is well established in other areas of medicine such as cardiac and orthopaedic surgery, but there are safety concerns for its use in obstetric practice. Highlighted risks included fetal cells infusing into the maternal circulation and potentially causing haemolytic disease (the baby’s blood cells being destroyed) in a future pregnancy.

NICE advised it’s only performed by experienced professionals and women informed of complication risk.

The Royal College of Obstetricians and Gynaecologists (2016) advised that emergency use of cell salvage is considered for women with postpartum haemorrhage after caesarean.  

What are the implications?

The findings suggest there isn’t a case for the routine set-up of cell salvage for women undergoing caesarean. That’s not to say it doesn’t still have a role in the emergency management of haemorrhage or very high-risk circumstances when resources and expertise are available.   

The trial was conducted 2013-16 and practice is evolving. Other options to manage maternal haemorrhage are: giving blood fluid (plasma) infused with clotting factors or giving tranexamic acid which prevents blood clots from breaking down.

The finding that cell salvage was associated with a small increase in the chance of RhD-negative mothers being exposed to RhD-positive fetal blood highlights a need for long-term vigilance and perhaps further study.

Citation and Funding

Khan SK, Moore PAS, Wilson MJ, et al. Cell salvage and donor blood transfusion during caesarean section: A pragmatic multicentre randomised controlled trial (SALVO). PLoS Med. 2017;14(12):e1002471.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 10/57/32).

Khan KS, Moore P, Wilson M, et al. A randomised controlled trial and economic evaluation of intraoperative cell salvage during caesarean section in women at risk of haemorrhage: the SALVO (cell SALVage in Obstetrics) trial. Health Technol Assess. 2018;22(2):1-88.

Bibliography

NHS Digital. NHS Maternity Statistics, England 2016-17. Leeds: NHS Digital; 2017.

NICE. Intraoperative blood cell salvage in obstetrics. IPG144. London. National Institute for Health and Clinical Excellence; 2005.

Mavrides E, Allard S, Chandraharan E, et al on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG 2016;124:e106-49.

JPAC. UK Cell Salvage Action Group. London. Joint United Kingdom Blood Transfusion and Tissue Transplantation services Professional Advisory Committee.

The Lancet. Woman: reducing maternal deaths with tranexamic acid. 2017;389(10084):2081.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

Published on 19 December 2017

Khalid S. Khan , Philip A. S. Moore, Matthew J. Wilson, Richard Hooper, Shubha Allard, Ian Wrench, Lee Beresford, Tracy E. Roberts, Carol McLoughlin, James Geoghegan, Jane P. Daniels, Sue Catling, Vicki A. Clark, Paul Ayuk, Stephen Robson, Fang Gao-Smith, Matthew Hogg, Doris Lanz, Julie Dodds, on behalf of the SALVO study group

PLoS Medicine , 2017

Background Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. Methods and findings We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference −1.03, 95% CI −2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. Conclusions The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant.

The Rhesus (RhD) system denotes whether a person has a D antigen on the surface of their red blood cells. Most people do and are said to be RhD positive.

If a woman is RhD negative and is carrying an RhD positive baby, there is little risk during a first pregnancy as fetal and maternal blood is separated. But if the baby’s blood gets into the mother’s circulation during delivery, this will cause her to develop antibodies against the ‘foreign’ RhD antigen present on the baby’s blood cells. These antibodies could then harm another RhD positive baby in any future pregnancies.

Expert commentary

The women in the cell salvage group required less donor blood transfusion, but this was not statistically significant.

Those studied were at lower risk of requiring transfusion than women who are currently considered for cell salvage, which should be remembered when interpreting the results.

Two serious adverse events potentially related to the use of cell salvage were reported. These were thought to be related to the use of a leukocyte depletion filter.

Clinicians should not rule out the use of cell salvage on the basis of this trial but should recognise that the clinical effectiveness of this intervention is uncertain.

Dr Rhona Hughes, Consultant Obstetrician, Royal Infirmary, Edinburgh

Expert commentary

Cell salvage is of accepted benefit in high risk cases such as placenta accreta, where blood loss may be high, in women who do not want donor blood. However, it is increasingly being used in the more routine cases on a ‘just in case’ basis. This has the advantage of increasing the expertise within the unit but is not of proven clinical benefit. This paper confirms amount of blood salvaged and replaced is low in these situations and does not support its routine use for clinical benefit. There may also be significant cost implications.

Professor James Walker, Department of Obstetrics & Gynaecology, Leeds Institute of Biomedical & Clinical Sciences, St James University Hospital