The COVID-19 pandemic put a spotlight on the patchwork system of blood collection that has developed around the world – and how to improve it.
More than 100 million blood donations are collected around the world each year, but access to this life-saving resource depends very much on where a patient lives. The World Health Organization (WHO) estimates that 40% of blood is collected – and stays – in high-income countries, which account for just 16% of the world's population.1
These high-income countries provide the model for safe and sustainable blood donation. In places like the U.S. and much of Europe, blood donation occurs regularly from unpaid, voluntary donors. Blood is tested for several transfusion-transmitted diseases, and the entire process is regulated in a centralized fashion. In other parts of the world, blood collection falls far short of these ideals, making the blood supply fragile and vulnerable to emergencies.
The blood donation rate in high-income countries is 31.5 donations per 1,000 people, according to the WHO, contrasted with a rate of 5.0 donations per 1,000 people in low-income countries.1
Add the COVID-19 pandemic, which has isolated potential blood donors, and the availability of blood is limited further, causing treatment delays for patients with hemoglobinopathies who require regular transfusions.
"With volunteers' fears that they are going to catch an infection and that the sites where they are going to donate may not be adequately protected from COVID-19 transmission, many countries saw a dip in volunteer donations," Isaac Odame, MBChB, MRCP, hematology section head at the Hospital for Sick Children (SickKids) in Toronto, told ASH Clinical News. "In Ghana, for example, the health system saw a dip of nearly 40%," said Dr. Odame, who is also medical director of the Global Sickle Cell Disease Network at SickKids.
The decrease in blood availability has real-world consequences for patients with sickle cell disease (SCD) living in Africa, he explained. "There is a blood transfusion system that is already weak, that is already overstretched, and then the COVID-19 pandemic reduces donation significantly," he said. "And then patients with SCD who, in addition to all the other requirements for blood transfusion, may catch COVID-19 and require more transfusions than usual."
ASH Clinical News spoke with Dr. Odame and other transfusion experts to understand blood donation and transfusion practices around the world and how they are meeting preexisting challenges that the current pandemic has only heightened.
A Dropping Blood Supply
In tracking the effect of the COVID-19 pandemic on the global blood supply, the WHO has reported that the overall level of blood collection was lower in 2020 than 2019. Several factors have caused this slowdown. First, there are fewer eligible donors due to COVID-19 infection or exposure. Safety protocols limit the number of people who can come into hospitals and the number of blood drives that were typically conducted at workplaces and schools, while the ongoing health crisis has created a shortage of staff necessary to collect blood.
While the drop in blood donations appears to be a global phenomenon, countries have had variable success in keeping collection numbers high enough to meet demand. For example, many countries report that the reduction in donor numbers has been largely offset by reductions in demand for transfusion. However, these typically are high-income countries with well-established blood donor recruitment programs, Junping Yu, a technical officer on the WHO Blood and Other Products of Human Origin team, explained to ASH Clinical News.
"They rely on regular blood donors and are more likely to be successful when they ‘call on' the public and blood donors," Mr. Yu said. "For example, many of these countries had also introduced the use of social media to [contact] donors individually for a personal appointment."
Meanwhile, many lower-income countries have reported a severe interruption in the frequency and quantity of blood collected. The main source of blood in these countries is often so-called family/replacement donors who donate blood to meet the needs of family and friends who require transfusion. The lack of a voluntary donor culture and infrastructure in these countries makes it more difficult to collect donations in times of crisis, Mr. Yu said.
Another hurdle for low-resource settings during the pandemic has been a lack of consumables, equipment, and personal protective equipment (PPE), due to closed borders and interruptions in air travel.
In Latin America, the impact of COVID-19 on blood supply has been mixed. So far, declines in blood collection have not resulted in critical shortages, according to Mauricio Beltrán Durán, regional advisor for Blood Services and Organ Transplants for the Pan American Health Organization (PAHO).
In May 2020, PAHO asked its member countries if they had seen a decrease in blood availability and whether it affected clinical care. Seven countries responded, representing about 70% of Latin American and Caribbean countries. Two countries reported a decrease in blood availability of more than 40%, two reported decreases between 20% and 40%, and three had reductions of less than 20% in availability, compared with 2019 levels.
"The challenge was common to all countries as the pandemic spread, but the impact differed according to the capacities and measures taken by the countries for containment," Mr. Beltrán Durán told ASH Clinical News. "Countries that reported an impact of less than 20% of the decrease in blood availability were those with voluntary donations greater than 60% and with a processing capacity greater than 8,000 units per year, per bank, meaning greater capacity."
There have been some positive developments in Latin America during COVID-19, said Jose Ramiro Cruz, DSc, an independent consultant on blood safety issues who has worked extensively in Latin America. For example, the pandemic has forced countries to make changes that were beneficial overall, such as increasing mobile collection and building up communication efforts with donors.
"The relationship between the blood services and the donors is very, very weak in the Ibero-American region, but [measures taken during the pandemic] have strengthened it," Dr. Cruz said.
In Africa, where blood availability was stretched thin even before COVID-19, Dr. Odame said the pandemic in 2020 had not had the devastating consequences he had feared. However, since the beginning of 2021, African countries have experienced a surge in COVID-19 cases, putting further stress on blood availability on the continent.
Conflicting Messages
Blood availability during the COVID-19 pandemic has not only been a problem for the developing world. Konstantinos Stamoulis, MD, scientific director of the Hellenic National Blood Transfusion Centre in Athens, said he has also seen these problems play out in Greece.
Part of the problem is the contradictory public health message that officials have wrestled with during COVID-19. "We say to the people if you want to be safe, stay home," Dr. Stamoulis said, "and then the transfusion service says, ‘If you care about your fellow citizens, get out and donate blood.'"
He has seen reluctance among health care providers to initiate blood collection and among donors to give blood. The result is a significant drop in donations across Greece. Every time the country had a lockdown order, it saw a decline in blood donations, with lows of 18% in April 2020 and 15% in November 2020. This has delayed care for many patients with thalassemia, a condition that affects roughly 8% of the Greek population.
Greece needs a significant amount of blood each month just to meet the transfusion needs of patients with thalassemia, who typically need transfusion with two units of blood every 15 days. This requires donations from about four donors per patient each month, which is primarily handled through donations from family members and friends of patients. The Greek government also imports a small amount blood each month from Switzerland, Dr. Stamoulis said.
"The impact [of the COVID-19 pandemic] differed according to the capacities and measures taken by the countries for containment."
—Mauricio Beltrán Durán
Since COVID-19 has cut into blood donations, including family/replacement donation, there is not always enough blood to transfuse patients with thalassemia in a single session, he explained. Instead, physicians transfuse a single unit of blood at a time and bring the patient back in four to five days, with the hope that the hospital will have a greater supply by that point. "It's not just that we are delaying transfusion, we are also bringing them into the hospital environment to be transfused much more often," he said.
At the beginning of the pandemic, the Greek Ministry of Health postponed elective surgeries, which was effective in lowering the demand for blood. But, because the Greek blood system comprises roughly 30% family/replacement donations, the delay in scheduled surgeries also resulted in family/replacement donors staying home, lowering the overall supply of blood. "The lesson is that you have to be careful what you ask people to do," he said.
Volunteers: The System's Lifeblood
Who donates blood – and why – is a long-standing question that experts say affects blood availability and safety. The WHO asserts that unpaid, voluntary donors represent the lowest-risk population, as they do not have an incentive to conceal an adverse health condition. Since 1975, the WHO has asked all countries to aim to obtain all blood through voluntary, unpaid donors.2
The WHO and the International Federation of Red Cross and Red Crescent Societies have reiterated that achieving 100% unpaid, voluntary blood donation ensures that the blood supply is self-sufficient, sustainable, and safe. In a 2010 report, the organizations outlined strategies for phasing out family/replacement blood donation and eliminating paid donation.3
"Without a system based on voluntary, unpaid, blood donation – particularly regular voluntary donation – no country can provide sufficient blood for all patients who require transfusion," the report stated.
Many countries are progressing toward voluntary donation systems. In a 2020 report, the WHO found that, from 2013 to 2018, blood donations from voluntary unpaid donors increased by 7.8 million across 156 countries. The biggest jumps occurred in the Americas (25%) and Africa (23%).1
Seventy-nine countries (mostly high- and middle-income) collected more than 90% of their blood supply from voluntary unpaid donors. However, in 56 countries, more than half of the blood supply is dependent on family/replacement and paid blood donors. Just 16 countries reported paying for blood donations in 2018, according to the WHO, accounting for about 276,000 donations.
In Greece, where family/replacement donations account for so much of the blood supply, the practice is a barrier, Dr. Stamoulis said. Since donors know their blood will be needed for a family member, they are less willing to donate to a stranger. This cuts into the potential pool of voluntary donors. "All of these things were accentuated with COVID-19," he said.
In Latin America, the percentage of donations from volunteers has been inching higher in recent years, increasing from 44.2% in 2015 to 46.1% in 2017.4 That year, Latin American countries obtained more than 1.6 million blood units from volunteer donors who gave regularly, which represented 34.9% of voluntary donations, according to a report from PAHO.4
Some countries have been able to transition to a voluntary donor system relatively quickly. In Nicaragua, for example, the rate of blood collection was 106.6 units per 10,000 people in 2007, with a voluntary donation rate of 39%. Health authorities there took aggressive action to pursue "self-sufficiency" by eliminating replacement donation, consolidating blood processing to two centers, recruiting and educating regular blood donors, and expanding mobile blood collection. Replacement donation ended in 2009 and, by 2010, the country had achieved 100% voluntary donation. Collection rates improved at the same time, increasing to 125.9 units per 10,000 people in 2011.5
The combination of terminating family/replacement donation and educating donors was key to the success in Nicaragua, Dr. Cruz explained. "People trust the system," he said. "Patients don't pay for blood and blood is provided to everyone."
He added that it is important for countries in Latin America and elsewhere to consider the nonclinical challenges related to voluntary blood donation. In rural areas, for instance, transporting patients to the hospital can take two to three days. In those cases, the introduction of mobile blood units is essential.
High rates of donor deferral (when individuals do not meet the criteria used to protect the health and safety of both the donors and recipient), also can erode trust among potential donors, Dr. Cruz said. In 2015, deferrals for voluntary blood donors were about 15% to 25% for replacement donors in Ibero-American countries. Hospitals deferred donors for unjustified reasons such as lipemic plasma, inappropriate veins, recent food intake, menstruation, and over-stocked blood type.6
Dr. Cruz stressed that the best way to maintain an adequate blood supply with voluntary, unpaid donors is to forge a relationship with the donors and encourage them to donate every six months. This option is more practical than trying to increase the number of sporadic donors and storing that blood, which expires. But cultivating the donor base requires building relationships with individual donors and having the necessary facilities to collect those donations, he said.
"Keeping the donors involved is important," Dr. Cruz said. "I feel good when I go to give blood and people thank me."
PEPFAR Funding Loss
A significant portion of blood donation in sub-Saharan Africa is still from family/replacement donors, but some countries have achieved or are close to achieving 100% voluntary donation, according to Christine Bales, vice president for consulting and global services at AABB's Division of Global Services.
Dr. Odame notes that implementing voluntary blood donation "has been an age-old problem." High- and middle-income countries have been able to tackle this issue, but it is a long-term challenge in low-income countries. "People [in low-income countries] don't consider themselves healthy enough to be able to donate blood and there is suspicion of the system," he said. "Culturally, giving blood is not something that many of these countries established. Replacement donation has been the main approach they have taken to meet the demands."
The national blood services in sub-Saharan African nations have been making some progress, but those gains require financial support, Ms. Bales said.
For example, Lesotho, a small country surrounded by South Africa, had almost achieved full voluntary donation when international funding to the country was cut in 2019.7 The main source of funding for blood safety in Africa has come through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). The program has provided millions of dollars in funding to national blood services in Africa to ensure the safety of its blood supply as part of its focus on HIV prevention.
Since the grants have ended, Lesotho is back to 70% to 80% family replacement donations, Ms. Bales explained. "It's very difficult; the blood supply is always a fragile commodity," she said. "We had made improvements, but were we done? No, not by far."
"[Increasing hydroxyurea access] is a fundamental way to reduce the demand for blood transfusions, which is obviously a challenge in many countries."
—Isaac Odame, MBChB, MRCP
"Blood centers in Africa were already stretched thin prior to COVID-19, which has been compounded by the loss of PEPFAR funding – not just in Uganda, but throughout Africa," said Aaron Tobian, MD, PhD, director of transfusion medicine at The Johns Hopkins University School of Medicine, who is conducting a clinical trial in Uganda to test whole blood pathogen technology to prevent transfusion-transmitted infections. "With PEPFAR pulling out, there were times when many blood systems throughout Africa did not have the money for all their screening for hepatitis B, hepatitis C, and HIV. It really created a conundrum of what to do in that situation."
Blood systems in Africa are now prioritizing maintaining the standards that were set five to 10 years ago, he said.
Strategies for Blood Sufficiency
One possible approach to dealing with a shrinking blood supply is to reduce the demand for blood, Dr. Odame said. For example, in Africa, putting patients with SCD on disease-modifying therapy, like hydroxyurea, has the potential to significantly reduce their need for transfusion.
He cited the REACH trial, which enrolled more than 600 young children with SCD in Angola, the Democratic Republic of Congo, Kenya, and Uganda. Children received a fixed dose of hydroxyurea daily for six months, followed by dose escalation for several years. The trial demonstrated that therapy could significantly increase levels of both hemoglobin and fetal hemoglobin, lowering the need for transfusion.8
"I, and others, have been making the case that if ever there was a time to make hydroxyurea accessible to patients living with sickle cell disease in Africa, it is now, because it is a fundamental way to reduce the demand for blood transfusions, which is obviously a challenge in many countries," Dr. Odame said.
While the efficacy of hydroxyurea has been proven in clinical trials, implementing it as a standard of care in Africa is a more substantial undertaking, he noted, which involves educating clinicians, health systems officials, and the public on disease-modifying treatments as a cost-effective strategy in SCD.
"Meeting this challenge, said Dr. Odame, "requires many multi-sectorial partnerships to strengthen these health systems, train and educate providers at all levels of care, and be able to set up systems to make hydroxyurea accessible and affordable." —By Mary Ellen Schneider
References
- WHO. Blood safety and availability. Accessed February 7, 2021, from https://www.who.int/news-room/fact-sheets/detail/blood-safety-and-availability.
- WHO. WHA28.72 Utilization and supply of human blood and blood products. Accessed February 7, 2021, from https://www.who.int/bloodsafety/en/WHA28.72.pdf.
- WHO and International Federation of Red Cross and Red Crescent Societies. Towards 100% voluntary blood donation: a global framework for action. Accessed February 7, 2021, from https://apps.who.int/iris/handle/10665/44359.
- Pan American Health Organization. Supply of Blood for Transfusion in Latin America and Caribbean Countries 2016-2017. Accessed February 7, 2021, from https://iris.paho.org/handle/10665.2/52966.
- Berrios R, Gonzalez A, Cruz JR. Achieving self-sufficiency of red blood cells based on universal voluntary blood donation in Latin America. The case of Nicaragua. Transfus Apher Sci. 2013;49(3):387-396.
- Cruz JR. Transfusion safety: lessons learned in Ibero-America and considerations for their global applicability. Intl J Clin Transfus Med. 2019;7:23-37.
- Kaiser Family Foundation. The U.S. President's Emergency Plan for AIDS Relief. Accessed February 7, 2021, from https://www.kff.org/global-health-policy/fact-sheet/the-u-s-presidents-emergency-plan-for-aids-relief-pepfar/.
- Tshilolo L, Tomlinson G, Williams TN, et al. Hydroxyurea for children with sickle cell anemia in sub-Saharan Africa. N Engl J Med. 2019;380(2):121-131.