Tag: blood transfusion

Lower RBC Transfusion Volume in Neonate ECMO Reduces Mortality

Photo by Christian Bowen on Unsplash

A new study indicates that for newborns in respiratory failure supported by ECMO, the greater volume of the red blood cell (RBC) transfusions that the babies receive, the higher their mortality rate.

“In order for the baby to survive on ECMO, they need red blood cells, they need platelets, they need plasma,” said Dr Brian Stansfield, neonatologist at the Medical College of Georgia and Children’s Hospital of Georgia (CHOG) “You have to have sufficient blood volume to make the whole system work. But there is also increasing evidence that if you can get by with less, that is probably more.”

“We think this supports the overall trend of being more restrictive in transfusion practices and being even more mindful about when you give transfusions and when you don’t while a child is on ECMO,” said Dr Jessica Gancar, neonatology fellow at MCG and CHOG.

The clinicians are the most confident this holds true for ECMO with babies in respiratory failure, while the relationship is more tentative for other causes. Respiratory failure makes up the largest population of newborns needing ECMO. The findings are another good reason for ECMO centres to reexamine when they transfuse babies, the clinicians point out.
Haematocrit levels (red blood cells to volume ratio) are a key measure typically used to determine whether to transfuse.

“Our transfusion practice is when the haematocrit hits 35% we will transfuse,” said Dr Stansfield. “Most ECMO centres still have a threshold of 40%, which means they are transfusing more. Others transfuse at 30%. So in our program we also have to ask the question if we are accepting some unnecessary risks. Could we get by with less?”                                                                    
They looked at 248 newborns treated from 2002-19 at CHOG with an overall survival rate of 93%.

They analysed their medical records for any relationship between blood product transfusion and death and complication rates in these babies.  

“We identified a clear linear relationship between mortality and red blood cell transfusion volume. Specifically, for every transfusion of red cells while on ECMO, a baby’s chances of survival decreased by 14%,” said Dr Gancar.

Plasma or platelet transfusions did not correlate with increased mortality. The findings are being presented during the Southern Society for Pediatric Research meeting.

“While blood product transfusions are necessary for critically ill newborns on ECMO, transfusions are given in response to ‘understudied, arbitrary thresholds and may be associated with significant morbidity and mortality,’” they write in their abstract.

“I think we are getting to the point, with neonatal ECMO in particular, where we are transitioning from how do we prevent death by intervening with ECMO – for a long time that was the question – to asking questions like once you are on ECMO, how do we make outcomes better,” said Dr Stansfield. “We already know that going on ECMO is a risk, that all the blood and other products we are giving at the start of ECMO is a risk, but could we limit some of the additional risk?”

ECMO requires essentially doubling the baby’s blood volume, said Dr Gancar. Just priming the pump typically requires two packs of red blood cells along with other select additives like albumin and heparin. Typically two more packs of platelets as well as fresh frozen plasma are given once the baby is on ECMO. Other blood product transfusions may follow over their course on ECMO, which averages three to seven days at CHOG.

At CHOG, the neonatal specialists work hard to give as few transfusions as possible and some babies, typically those on ECMO five days or less, may not require any exposures beyond the pump priming; others, typically the sickest babies, may be given five to 10 transfusions over their treatment course. They note that their study adjusted for sickness severity so that could not explain the increased mortality they found associated with more red blood cell transfusions.

Blood transfusion is known to increase mortality risk in essentially any disease process, Dr Gancar said, as they can prompt problems like increased inflammation, despite modern typing procedures to help ensure a good match between donor and recipient.

In these babies that risk seems linked to red blood cells, which have to be separated from factors they normally circulate with, be exposed to preservatives and may have a protracted storage time before they are transfused.  

Decades of success with ECMO has the CHOG team confident about its value in helping babies overcome potentially deadly but also potentially reversible problems like meconium aspiration, but they still have a “healthy respect” for the technique, Dr Stansfield said.

They rule out traditional therapies first like using a ventilator to support breathing and nitric oxide to dilate the lungs and blood vessels. Dr Stansfield notes that the number of babies needing ECMO has fallen over the years as neonatal teams like theirs have improved.

But sometimes: “We run out of options unfortunately and that is when we bring in ECMO,” said Stansfield. While the team has one of the longest and best track records in the nation with ECMO, the facts remain that it requires surgery on the baby’s neck to place a small cannula in their internal jugular vein and sometimes a second one placed in the carotid artery to return the warmed and oxygenated blood back to the baby. Both those blood vessels no longer function afterward.

Approaches like ventilators are more straightforward and less invasive, Dr Stansfield said. “But the realisation is that we know there is a small percentage of kids that need more intensive therapy,” he said.  

Source: EurekAlert!

The Secret of ‘Rejuvenating’ Blood Transfusions Between Mice

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Researchers have identified an important mediator of youthfulness in mouse muscle, which explains the ‘rejuvenating’ blood transfusions effect between young and old mice. The discovery could also lead to new therapies for age-related muscle loss.

Published in Nature Aging, the study showed that circulating shuttles called extracellular vesicles, or EVs, deliver genetic instructions for the longevity protein known as Klotho to muscle cells. Reduced muscle function and repair in old mice may be driven by aged EVs, which carry fewer instructions than those in young animals.

The findings help further as to understanding why muscle regeneration capacity diminishes with age.

“We’re really excited about this research for a couple of reasons,” said senior author Dr Fabrisia Ambrosio. “In one way, it helps us understand the basic biology of how muscle regeneration works and how it fails to work as we age. Then, taking that information to the next step, we can think about using extracellular vesicles as therapeutics to counteract these age-related defects.”

Decades of research have shown that when old mice are given blood from young mice, youthful features are restored to many cells and tissues. But until now, it was unclear which components of young blood confer these rejuvenating effects.

“Amrita Sahu releaseWe wondered if extracellular vesicles might contribute to muscle regeneration because these couriers travel between cells via the blood and other bodily fluids,” said lead author Dr Amrita Sahu. “Like a message in a bottle, EVs deliver information to target cells.”

Ambrosio and her team collected serum from young mice and injected it into aged mice with injured muscle. Mice that received young serum showed enhanced muscle regeneration and functional recovery compared to those that received a placebo treatment, but the serum’s restorative properties were lost when EVs were removed, indicating that it is these vesicles which deliver the beneficial effects of young blood.

The researchers then found that EVs deliver genetic instructions, or mRNA, encoding the anti-ageing protein Klotho to muscle progenitor cells, important stem cells for muscle regeneration. EVs collected from old mice carried fewer copies of Klotho instructions than those from young mice, causing muscle progenitor cells to produce less of this protein.

With advancing age, muscle doesn’t recover from damage as well because scar tissue is laid down. In earlier work, Ambrosio and her team showed that Klotho is an important regulator of regenerative capacity in muscle progenitor cells and that this protein declines with age.

The new study shows for the first time that age-related shifts in EV cargo contribute to depleted Klotho in aged stem cells, suggesting that EVs could be developed into novel therapies for healing damaged muscle tissue.

“EVs may be beneficial for boosting regenerative capacity of muscle in older individuals and improving functional recovery after an injury,” said Ambrosio. “One of the ideas we’re really excited about is engineering EVs with specific cargoes, so that we can dictate the responses of target cells.”

Beyond muscles, EVs also could help reverse other effects of ageing. Previous work has demonstrated that young blood can boost cognitive performance of aged mice.

Source: University of Pittsburgh

Female Blood Donors Better for Very-low-birthweight Transfusions

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The sex of adult blood donors may affect the risk of common complications in transfusions of red blood cells (RBCs) to premature or very-low-birthweight infants while in the neonatal intensive care unit (NICU), according to new research.

Anaemia is common in premature or very-low-birthweight infants, often requiring an RBC transfusion. Common negative outcomes that can occur with very low birth weight infants include necrotising enterocolitis, lung damage or retinopathy of prematurity. Studies provided conflicting evidence of transfusions being a risk factor.

The study was led by Dr Ravi Patel is director of neonatal research in the Department of Pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta. Dr Patel and colleagues followed 181 very-low-birth-weight infants at three hospitals from 2010 to 2014. The infants were selected who received RBC transfusions from only male donors or only female donors.\

The study, published in JAMA Network Open, found that a typical very-low-birth-weight infant who received red blood cell transfusion from only female donors had a three times lower risk of negative outcomes than one who received red blood cells from only male donors.

Increasing donor age increased the protective effect of female donors. Some potential explanations for the protective effect could be reduced breakdown during storage of RBCs from female donors, along with less inflammation and more antioxidant capacity, the authors wrote.

RBC transfusion is common, according to Dr Patel, with about half of very low birth infants receiving at least one RBC transfusion while in the NICU. RBC transfusion is necessary to treat anaemia related to prematurity. In rare circumstances, this can lead to an infection or transfusion reaction. It is uncertain whether RBC transfusion increases the risks of some adverse clinical outcomes.
  Is it correct to say that the suspected mechanism for the difference in risk has to do with the characteristics of the RBCs, rather than immune differences, the suspected reason for the reverse effect in adults?

Future research should investigate inflammation or antioxidant capacity of red blood cells since these mechanisms may differ from adults, Dr Patel suggested.
Should their findings that age and sex have an effect on transfusion outcomes be confirmed, the next step would be transfusing blood from only males or only females, which could inform changes in practice.
Source: Emory University

Urgent Plea as COVID Leaves SA Blood Stocks Critically Low

The Citizen reports that blood stocks in South Africa are running critically low, and the South African National Blood Service is appealing to businesses, universities, schools and churches to help achieve its minimum requirement of 4 000 units a day.

Demand has surged since lockdown as elective surgeries are now being conducted, as well as a return to increased numbers of accidents.

A statement released by the SANBS reads: “Blood stocks have dropped to critically low levels. The immediate impact is an inability to issue blood in emergencies and the possible loss of lives. We need healthy donors to give blood now.”

Dr Karen de Berg of the SANBS says that the shortfall is resulting from not being able to station blood donation drives at businesses, universities and schools. The SANBS is appealing for donors to visit their website or social media pages to locate their nearest blood donation centres, and is hoping to set up donation drives at churches and petrol stations.