Tag: blood transfusion

Categories : Cardiovascular DiseaseTags :

Brain Haemorrhage Risk Factor could be Transmissible via Blood Transfusion

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A major study led by researchers at Karolinska Institutet suggests that a possible cause of spontaneous brain haemorrhage could be transmitted via blood transfusion. At the same time, it is very unlikely that anyone should suffer a brain haemorrhage after receiving donated blood, according to the study findings which are published in JAMA.

A common cause of spontaneous, recurring brain haemorrhages is the vascular disease cerebral amyloid angiopathy (CAA), in which proteins accumulate along the small blood vessels of the brain. Several studies have shown that CAA can be transferred from one individual to another through neurosurgery and probably via treatment using a certain type of growth hormone.

Few affected individuals

This new study led by researchers from Karolinska Institutet shows that patients who have received blood from donors who later suffered recurring brain haemorrhages are more than twice as likely to suffer a brain haemorrhage themselves.

The findings suggest that some factor that can give rise to spontaneous brain haemorrhages can be spread through blood transfusion. However, as only 0.1% of the donors in the study subsequently suffered recurring brain haemorrhages there were consequently only a few affected patients.

“Blood transfusions are relatively common, which makes possible negative effects an important public health issue,” says the study’s last author Gustaf Edgren, researcher at the Department of Medicine, Karolinska Institutet (Solna) and specialist physician at Södersjukhuset. “However, in this case, it’s very unlikely that you’d suffer a brain haemorrhage from something transmitted through a transfusion.”

CAA could be transmissible

According to the researchers, the most important implication of the study is instead that it adds further support to the hypothesis that CAA can be transmitted between individuals, which, if true, can have consequences in several fields.

The study drew on the data of more than a million patients the Swedish-Danish transfusion database SCANDAT, which contains data on blood donors and patients receiving a transfusion from the 1970s onwards. The primary analyses were conducted in Sweden and then repeated with the Danish data, with almost identical results.

Confirmation needed

The researchers now hope to corroborate the hypothesis that the link between brain haemorrhage and blood transfusion concerns CAA. They will therefore be examining samples from the Danish Blood Donor Study biobank to see if they can identify aberrant proteins associated with the disease.

The plan is also to obtain CAT and MR scans from the affected donors and patients to see if they might also be able to support the hypothesis.

“This study does not demonstrate causality, so the observed increase in risk could depend on other factors,” says the study’s first author Jingcheng Zhao from Dr Edgren’s group at Karolinska Institutet. “More research is needed to confirm our findings and understand the potential underlying mechanism.”

Source: Karolinska Institutet

Categories : Injury & TraumaTags :

Could A Perfume Ingredient Stop Coagulopathy in Massive Bleeding?

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The chances of surviving massive blood loss from a traumatic injury such as a gunshot wound are around 50%. To survive, a patient urgently needs a large infusion of blood and coagulation at the wound to stop the bleeding.

The problem is one of these solutions prevents the other. Introducing a large amount of blood to those suffering a massive haemorrhage impairs the blood’s ability to clot, a condition known as coagulopathy.  

Now, Tulane University researchers have uncovered the cause of coagulopathy in trauma victims receiving a blood infusion. They also found that a synthetic compound called dimethyl malonate – often used in perfume manufacturing – has the potential to stop coagulopathy during a massive hemorrhage. The researchers’ findings are part of a new study published in Science Advances.

“Coagulopathy of trauma is a major contributor to mortality, but no treatment has shown to be fully effective,” said Olan Jackson-Weaver, PhD, assistant professor of surgery at Tulane University School of Medicine and corresponding author on the study. “We were getting 60 percent mortality with our animal model. With dimethyl malonate, we got zero percent mortality, and the coagulopathy completely went away.”

Recent studies have shown that coagulopathy during massive haemorrhage treatment is most likely caused by the shedding of the glycocalyx, a barrier of sugars that surrounds and protects cells. In blood vessels, the glycocalyx lines the vessel walls and prevents blood from clotting. However, this is the first study to identify the cellular events that cause the glycocalyx to be ripped apart.

The study found that a large infusion of blood creates a spike in cellular metabolism which causes a change in structure to the cell membrane. This exposes the glycocalyx, allowing it to be chewed up by enzymes and mixed into the bloodstream, where it prevents clotting.

“People have been trying to figure out ways to move the needle a little bit on the death rate from massive haemorrhage for the last 20 or so years and nothing has really worked,” Jackson-Weaver said. “We’re hopeful that understanding these cellular-level events can help to develop something that actually does make a big difference.”

In animal models, dimethyl malonate was effective at inhibiting excessive cellular metabolism, which prevented the glycocalyx from shedding and causing coagulopathy.

But Jackson-Weaver said more research needs to be done to determine if dimethyl malonate is safe for humans or if an equivalent drug that targets cellular metabolism can be developed.

“We’ve established this pathway that causes coagulopathy, so if we can target it therapeutically with a pre-hospital drug or injection, we can hopefully save some lives,” Jackson-Weaver said.

Source: Tulane University

Categories : Medical Research & TechnologyTags :

World First Trial of Lab-grown Red Blood Cells for Transfusion

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In a world first, researchers have launched a clinical trial of lab-grown red blood cells for transfusion into another person. These manufactured blood cells were grown from stem cells from donors, for transfusion into volunteers in the RESTORE randomised controlled clinical trial.

If our trial is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care

Professor Cedric Ghevaert, chief investigator

If the technique is proven safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders such as sickle cell and rare blood types. It can be difficult to find enough well-matched donated blood for some people with these disorders.

To produce the lab-grown blood cells, stem cells are first magnetically extracted from a normal 470ml blood donation. These stem cells are then coaxed into becoming red blood cells. Over the three week process, an initial pool of about half a million stem cells generates 50 billion red blood cells.

Chief Investigator Professor Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the University of Cambridge and NHS Blood and Transplant, said: “We hope our lab grown red blood cells will last longer than those that come from blood donors. If our trial, the first such in the world, is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care.”

Professor Ashley Toye, Professor of Cell Biology at the University of Bristol and Director of the NIHR Blood and Transplant Unit in red cell products, said: “This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells. This is the first-time lab grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells perform at the end of the clinical trial.”

The trial is studying the lifespan of the lab grown cells compared with infusions of standard red blood cells from the same donor. The lab-grown blood cells are all fresh, so the trial team expect them to perform better than a similar transfusion of standard donated red cells, which contains cells of varying ages.

Additionally, if manufactured cells last longer in the body, patients who regularly need blood may not need transfusions as often. That would reduce iron overload from frequent blood transfusions, which can lead to serious complications.

The trial is the first step towards making lab grown red blood cells available as a future clinical product. For the foreseeable future, manufactured cells could only be used for a very small number of patients with very complex transfusions needs. NHSBT continues to rely on the generosity of donors.

Co-Chief Investigator Dr Rebecca Cardigan, Head of Component Development NHS Blood and Transplant and Affiliated Lecturer at the University of Cambridge, said: “It’s really fantastic that we are now able to grow enough red cells to medical grade to allow this trial to commence. We are really looking forward to seeing the results and whether they perform better than standard red cells.”

Thus far, two people have been transfused with the lab grown red cells. They are well and healthy, and were closely monitored with no untoward side effects were reported. The amount of lab grown cells being infused varies but is around 5-10mls.

Donors were recruited from NHSBT’s blood donor base. They donated blood to the trial and stem cells were separated out from their blood. These stem cells were then grown to produce red blood cells in a laboratory at NHS Blood and Transplant’s Advanced Therapies Unit in Bristol. The recipients of the blood were recruited from healthy members of the NIHR BioResource.

A minimum of 10 participants will receive two mini transfusions at least four months apart, one of standard donated red cells and one of lab grown red cells, to see if the young lab-made red blood cells last longer than cells made in the body.

Further trials are needed before clinical use, but this research marks a significant step in using lab grown red blood cells to improve treatment for patients with rare blood types or people with complex transfusion needs.

Source: University of Cambridge

Categories : Cancer PaediatricsTags :

Blood Transfusion Increases Risks in Paediatric Cancer

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A study published in the Journal of Pediatric Hematology/Oncology found that blood transfusion is associated with adverse outcomes, including infection and higher rates of tumour recurrence — in paediatric solid tumour oncology patients following surgical removal of the tumour.

“Blood transfusion is obviously hugely important when used in the appropriate clinical scenario, but there are some downsides,” said study author Shannon Acker, MD, an assistant professor of paediatric surgery in the University of Colorado School of Medicine. “It’s pro-inflammatory and suppresses the immune system because your body reacts to foreign tissue. It can be a vital intervention, but I think we’re starting to be a little more thoughtful about giving patients blood products.”

Understanding paediatric blood transfusion

Dr Acker and colleagues pursued this research, in part, because while the effects of packed red blood cell (PRBC) transfusion in adult populations have been widely studied, data are sparser for paediatric patients.

“It’s fairly well-documented that in adult patients, perioperative blood transfusion for solid tumour resection is associated with certain adverse outcomes,” Dr Acker explained. “But paediatric cancers are more rare, so they’re more challenging to study. We need more data to understand whether what we know to be true in adult cancers is also true in paediatric cancers.”

Using retrospective data on more than 260 paediatric patients over 11 years, the researchers included malignant solid tumours removed by surgeons across all surgical disciplines. Dr Acker acknowledges that grouping different types of cancer into one study lessens the validity of the research because different cancers have different outcomes, “but we needed a place to start so we can begin working toward more collaborative, multi-centre paediatric oncology research,” she said.

Higher rates of complications

Of the 360 paediatric patients who underwent tumour resection, 194 received a blood transfusion within 30 days of surgery.

Analysing the data, they saw that children who received a blood transfusion had higher rates of post-surgery infectious complications, a shorter disease-free interval, and higher rates of tumour recurrence. They also adjusted for receiving pre-operative chemotherapy and still found that blood transfusion was associated with higher rates of post-operative infectious complications and a shorter disease-free interval.

No relationship was seen between tumour type and rate of infectious complications or disease-free interval.

Providing the best patient care

An aim of the research and its findings is to continue supporting and facilitating conversations and practices about patient care. “Packed red blood cells carry oxygen to the body and help tissues get the oxygen that they need,” Acker says. “They’re essential. It used to be common practice that if a surgeon was taking out a tumour and the patient was losing blood, they would immediately get two units.”

She added that blood transfusion now is recognised as “not a totally benign intervention, so instead of immediately giving a patient two units, we start with one and see if that leads to an appropriate response. Our research shows that each additional unit increases risk of adverse outcomes, so we want to continue being thoughtful in using this intervention.”

Acker adds that a further goal of the research is to work with members of paediatric oncology surgical consortiums to draw data from national and international centres. “The data we have are good, but I don’t think they’re enough to convince people to change institutional protocols. If we can get more validated, multi-centre data, we can begin to look at a more granular level at timing of transfusions and types of cancers so we can continue providing the best patient care.”

Source: University of Colorado Anschutz Medical Campus

Categories : Gender Injury & TraumaTags :

Sex of Red Blood Cell Donors Does not Affect Recipient Survival

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A study published in JAMA Internal Medicine shows that, after taking haemoglobin levels into count, sex and previous pregnancy of blood donors do not affect the survival of patients receiving red blood cell transfusions. Differences in recipient survival depend rather on the haemoglobin quantity in the transfusion, the researchers found.

Female donor sex and previous pregnancy are established risk factors for transfusion-related acute lung injury following plasma and platelet transfusions, which is a leading cause of transfusion-related mortality.

Previous studies have produced conflicting results as to how donor sex affects the recipient’s survivability in the recipient following red blood cell transfusion. Some studies have indicated higher mortality in patients who have received red blood cells from women, in men who have received red blood cells from women who have been pregnant, and in sex-mismatched transfusions. Other studies, however, have not reported such correlations.

This question has now been further explored by researchers from Karolinska Institutet in a register study of almost 370 000 patients in Sweden who received a red blood cell transfusion for the first time between 2010 and 2018.

The aim of the study was to see how the sex and previous pregnancy status of the donor affects survival in the recipient within two years from transfusion. It also looked at how the risk of needing more transfusions differed between patients who received red blood cells from female and male donors. Blood from women on average contains less haemoglobin than blood from men, meaning that more transfusions might be required to obtain the desired level of haemoglobin in a recipient.

The study demonstrates that the median value for haemoglobin was lower in female blood donors (135g/L than male (149g/L) and that patients who received blood from a woman had a 12% higher risk of needing another transfusion within 24 hours than blood from a man. However, this sex difference was eliminated when adjusting for the donors’ haemoglobin levels, which the researchers say was an expected effect that had not been factored into previous studies.

“When we take into account the lower haemoglobin levels in blood from women, we see no difference in survival among patients who received a blood transfusion from women compared with from men, regardless of how many times the female donors had been pregnant and of the patients’ sex and age,” said the study’s first author Jingcheng Zhao, adjunct researcher at Karolinska Institutet. “Differences in haemoglobin levels are a source of error that previous studies have not taken into consideration and that might explain the conflicting results that has been seen previously.”

Data for the study was drawn from national population, health and blood donor registries. The study also shows that donor sex is naturally randomly distributed in the patient material since no regard is paid to the sex and previous pregnancies of the donors by the blood donor centres when supplying blood. According to the researchers, this means that more far-reaching conclusions be drawn.

Dr Zhao said this allows them to determine causality. “We’ll now continue developing methods for studying causal relationships in transfusion epidemiology using observational data, on things like donor characteristics and how blood is handled. There’s still much we don’t know about blood transfusion and its effects.”

One limitation is that it was not possible to separately study transfusions where the red blood cells had not undergone leukoreduction (the filtering out of white blood cells), since this procedure has been standard in Sweden since the 1990s. The researchers therefore add a caveat about generalizing the conclusions to erythrocyte concentrates that have not undergone leukoreduction, which, however, is relatively uncommon now.

Source: Karolinska Institutet

Categories : PaediatricsTags :

Lower RBC Transfusion Volume in Neonate ECMO Reduces Mortality

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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!

Categories : AgeingTags :

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

Categories : PaediatricsTags :

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

Categories : UncategorizedTags :

Urgent Plea as COVID Leaves SA Blood Stocks Critically Low

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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.