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Europe needs 2 million extra donors of blood and plasma: How to find them?

2023; Wiley; Volume: 119; Issue: 2 Linguagem: Inglês

10.1111/vox.13540

1423-0410

Alice Simonetti, Cees Smit,

Organ Donation and Transplantation

In the summer of 2022, the European Commission published the Proposed Regulation on Substances of Human Origin (SoHO) [1] to update and replace the European Union (EU) Blood Directive [2] and the Tissues and Cells Directive [3]. The Regulation aims to protect donors and to ensure the safety and quality of blood, tissues and cells and to introduce measures to prevent shortages of these components produced from this precious material. With this Proposed Regulation, the European Commission renews its commitment to the principle of voluntary and unpaid donations. This principle prevents exploitation of donors—by risking their own health—without discouraging donations. On 18 July 2023, the ENVI Committee of the European Parliament voted on its amendments on the Draft Report by MEP Nathalie Colin-Oesterlé on the SoHO Regulation in the EU, with 59 votes in favour, 4 against and 4 abstentions [4]. The Report is currently scheduled to be voted by the Parliament in its plenary session on 11 September. Once adopted, it will constitute the Parliament's negotiating position for the trialogue talks with the Council. With regard to the discussion on voluntary and unpaid donations, the ENVI Committee has sharpened its position. MEPs insisted that EU countries could allow compensation or reimbursement for losses or expenses related to their donations, whereby MEPs have asserted that compensation should not be used as an incentive to recruit donors, nor should it lead to the exploitation of vulnerable people. They also wanted strict rules on advertising around SoHO donations, which should prohibit any references to financial rewards. Based on transparent criteria, Member States shall establish the conditions for such forms of compensation or reimbursement in national legislation, ensuring that they are financially neutral and consistent with the standards laid down in Article 54 of the new Regulation and in accordance with the principle of voluntary and unpaid donation. In this article, we calculate that Europe needs at least 2 million extra blood and plasma donors, who are willing to donate their blood and/or plasma several times a year. With these 2 million extra donors, Europe can continue to adhere to the principle of a blood transfusion system with voluntary non-remunerated (unpaid) donors (VNRDs) and be relatively self-sufficient. With these extra donors, Europe shall become less dependent on plasma derived from donors from other parts of the world, in particular from the United States. Furthermore, we explore the possibilities of a closer collaboration between Blood Collection Services and patient and donor organizations. New ways of communication are needed to motivate EU citizens on the importance of donating their 'red' blood and/or 'yellow' plasma. Also, stronger cooperation between the private and the public sector regarding the fractionation of the collected plasma needs to be considered. The support of individual EU Member States is not sufficient to reach this goal. Only a combined action plan of all EU Member States together with the European Commission can lead to success. This article reflects the perspective of representatives from the international donor community and from the patient community. We feel a joint responsibility to make a proposal that addresses the demand for plasma-derived medicinal products (PDMPs) for patient groups suffering from mainly rare diseases and that stimulates the donation of blood and plasma without underlying financial incentives. The EU SoHO Proposal includes an extensive evaluation period of the existing Directives for blood, tissues and cells based on consultations with EU Member States and relevant stakeholders. It also considers the recent COVID-19 pandemic, which has shown Europe's overdependence on non-EU ('third') countries for a variety of medical supplies (masks, swabs and protective clothing) and raw materials to produce medicines. In relation to plasma, Europe is dependent on ~40% or 4–5 million litres of American plasma from paid donors [5]. This dependency has grown during the last decades despite the 1985-formulated European principles of self-sufficiency and VNRD. We make a strong plea for strategic autonomy of Europe for plasma from VNRDs in line with the new EU proposal on SoHOs. Case studies in countries such as Italy, Belgium and Denmark have shown that sustainable supply of blood products is realistic with only VNRDs [6]. To reach this goal, Europe should expand its pool of blood and plasma donors and adjust the conceptualization of blood transfusion as a combination of 'red' blood (blood components such as red cells, platelets and plasma for transfusion) and 'yellow' blood plasma (plasma for fractionation needed to produce PDMPs such as albumin, immunoglobulins, clotting factors and serine protease inhibitors). In Box 1, we have explained the main developments in whole-blood and plasma collections in the previous decades. In the past century, the products of human blood were traced and isolated. Nowadays, most people are familiar with the possibility to donate blood. In a Blood Collection Service, a blood donor donates a maximum of 500 mL of whole blood at a time. This takes 30–45 min. After donation, the blood is separated into blood cells and plasma which can be used as plasma for transfusion or as plasma for manufacturing (recovered plasma). Plasma can also be donated using plasmapheresis. Whole blood of the plasma donor enters the plasmapheresis machine where plasma (source plasma) is separated from blood cells which are returned in the circulatory system of the donor. A plasma donation of 650–850 mL takes just over an hour. From source plasma and recovered plasma, PDMPs can be made with a long shelf-life. Examples are coagulation factors for haemophilia, albumin to treat burn wounds and liver problems and immunoglobulins for all kinds of immunological diseases. Plasma can be donated more often than blood. Most European countries rely on voluntary non-remunerated blood and plasmapheresis donors. Plasmapheresis donors are paid for their donations in four countries in Europe (Austria, Germany, Czech Republic and Hungary) and in the United States, Ukraine, China and others. The European Directorate for the Quality of Medicine (EDQM) recommends that a plasma donor may give 25 L of plasma per year, which corresponds to 33 donations per year. In the United States, a plasma donor can donate plasma 104 times per year, that is, twice weekly, and three times more than what the EDQM recommends. In recent years, the demand for red blood and yellow plasma in Europe has evolved in two different directions. The demand for red blood has decreased because of improved blood products and developments in patient blood management strategies, including cell-saving techniques during surgery and non-invasive surgical procedures. The demand for the yellow PDMPs has increased by ~8%–9% per year [7]. The increasing demand for and use of immunoglobulins is the main cause of the worldwide plasma shortage in both private and public sectors. This is especially detrimental for patient groups who depend on immunoglobulins for very different indications such as primary and secondary immune deficiencies and immunosuppressive problems or rare auto-immune and inflammatory diseases in the field of immunology, haematology, neurology and dermatology. In most EU countries, there is a shortage of immunoglobulin products. The long-standing, but still unresolved discussion among medical professionals about the indications for immunoglobulin use is unlikely to provide an answer to those patients, and their families, who are strongly dependent on these products [8]. There is an estimated 38% deficit of plasma in Europe, which is equivalent to 4–8 million litres of blood plasma [9]. This implies that around 2–4 million extra plasma donations are needed from donors who donate their whole blood at least twice a year or their plasma five times per year. Around 8 million extra donations can be obtained from these donors. Another 2 million extra donors of whole blood and plasma can prevent a further shortage of plasma in 2025, given the projected growth of PDMPs [9]. In a population of 447 million citizens in Europe, there are over 165 million eligible donors. This means that it must be possible to recruit 2–4 million extra donors. For a calculation of these figures, see Box 2. Currently, Europe has 15 million donors and 1400 Blood Collection Services, where 20 million units of whole blood are collected. Each year, EU patients are treated with 25 million blood transfusions to treat anaemia and during surgery or trauma care. The number of EU citizens who receive PDMPs is unknown. At present, the EU has a shortage of almost 3.8 million litres of plasma for manufacturing. In 2025, Europe will need almost 8 million litres of plasma to reduce dependence on plasma from the United States. With an extra need for 8 million litres of plasma, we propose that the collection of European source plasma should increase as follows: The calculation is conservative and global. One million whole blood donations of 500 mL each give 500,000 L of recovered plasma. One million plasma donations of 750 mL each give 750,000 L of source plasma. Whole-blood donations can be made up to four times a year, and plasma donations can be made up to a maximum of 33 per year. We calculate for whole-blood donors an average frequency of two donations per year and for plasma donors an average frequency of five donations per year. One million extra whole-blood donors, who give 500 mL recovered plasma and who donate twice a year, would generate 1 million litres of recovered plasma. One million extra plasma donors, who give 750 mL source plasma and who donate five times a year, would deliver 3,750,000 litres of source plasma. An ethical issue remains that with this amount of recovered plasma, there will be an excess of red cells and platelets for which there is no need in Europe. The recommended Action Plan should also address this issue. So, around 2 million extra whole-blood and plasma donors can solve the actual shortage of around 4 million litres of plasma in the EU. Another 2 million extra donors of whole blood and plasma can prevent the expected shortage in 2025. The combined Blood Collection Services in the EU should plan how to accommodate 2–4 million extra donors in their systems, given production efficiencies and scales of operation. These are quite different for whole-blood donors and plasma donors. A balanced mix of whole-blood donations and plasma donations is the preferred mode of action to keep existing donors and to attract new donors. For Blood Collection Services, it is preferable to have both types of donors in the same donor base. The advantage of low-frequency donations is the reduced individual donor burden, the increased donor health protection, the higher diversity of antibodies in a larger donor base and an increase of the total donor pool. The capacity per plasmapheresis centre is on average at least 20,000 L/year. To collect almost 4 million litres extra, some 200 extra plasmapheresis centres are needed with 15 or more beds. The new EU SoHO Regulation and especially the voting on the Amendments in the ENVI Committee once again stressed the principle of VNRDs. For more than 50 years, a debate has been going on about whether or not donors should be paid for their donation of blood and plasma. The ethical discussion on paid and unpaid donations was already raised in 1970 with the publication of the book The gift-relationship: from human blood to social policy by Richard Titmuss [10]. Titmuss is one of the founding fathers of the idea of the Welfare State and voiced his philosophy of altruism in social and health policy. Titmuss compared the British system of blood donations with systems in other countries and especially with the American one. In Britain, the system relies on VNRDs, while in the United States the plasma supply was and still is largely in the hands of for-profit enterprises. Already in September 1966, Titmuss had written about 'the hazards of blood commercialization to health, in particular patients' with the greater risks of contracting serum hepatitis and other blood-borne diseases because the health of paid donors was less reliable than that of volunteers' [11]. He intended to signal the dangers of the increasing commercialization of society. The US Food and Drug Administration (FDA) came out with a regulation in 1977 which required that each container of blood and blood components should bear the label statement 'Paid Donor' or 'Volunteer Donor'. This regulation was at that time based on the argument that blood from a paid donor was more likely to induce hepatitis in recipients than blood from a volunteer donor. This FDA labelling regulation is still in place [12]. A second important book was written by the Dutch journalist Piet J. Hagen, which was published in 1982 titled Blood: gift or merchandise [13]. The basic question Hagen wanted to answer was 'How (can) a sufficient and high-quality blood supply […] be organized in a responsible way and at reasonable costs'. His answer is not one-on-one, unlike Richard Titmuss's. Hagen is more realistic and states that if 'under the altruistic system in a certain country the needs of patients cannot be met adequately, one has to reconsider one's position'. After Hagen's book was published in 1982, the paid–unpaid discussion got a new dimension with the occurrence of thousands and thousands of HIV as well as HCV infections in the international haemophilia community. Countries with a dominant market share of clotting factor products manufactured from plasma from paid donors had a much higher share of these infections than those countries—especially in Europe—that used mainly haemophilia products prepared from plasma from VNRDs, such as Belgium, The Netherlands and the Scandinavian countries [14]. These transmissions of blood-borne infections caused enormous loss and grief in the haemophilia community. Still today, people suffer from the long-term effects of these viral infections, and in the United Kingdom the Infected Blood Inquiry shows how the UK Government nowadays has to deal with compensations issues [15]. A more recent overview on the discussion on paid versus unpaid donations was published in 2020 by the Fundacio Victor Grifols i Lucas with the title 'Ethics and plasma donation: an overview' [16]. In this overview, the final conclusion is that 'it is questionable as to whether plasma self-sufficiency is attainable in an individual country or region, at least in the short to medium term, and particularly if based exclusively on unpaid donations. The reality is that most countries have to purchase plasma products from companies that manufacture them using plasma from individuals who are remunerated for their donation, as the plasma obtained from each country's altruistic donors is not remotely sufficient to meet demand for these products'. In this overview, ethical considerations are pragmatically coupled with supply and demand issues, whereas the original altruistic approach by Richard Titmuss was coupled with social and health policies. The pragmatic approach in Grifols's overview is rather comparable with Piet J. Hagen's view. Although the United States is the main supplier of plasma from paid donors, and despite that FDA permits a high frequency of plasma donation up to 104 times per year, there are also in that country opponents of the paid plasma donation system. In his book What money can't buy: the moral limits of markets, Michael J. Sandel returns to Titmuss's basic assumptions that 'Markets are crowding out non-market norms' and that 'Commodification of blood offers a good illustration of the two objections to markets identified earlier—fairness and corruption' [17]. In Blood Money: the story of life, death and profit inside America's Blood Industry by Kathleen McLaughlin, she describes how Americans and their families with two or three jobs still live in a difficult financial situation and where payment for plasma donations is needed to survive [18]. In this regard, it is significant how the author warns that—even after what happened in the 1980s and 1990s with contaminated plasma—once again 'We've built an entire segment of global medicine upon the certainty that some number of American simply can't live on a regular income alone. They need money to supplement their wages and make their lives easier. And we don't exactly know if or how this frequent extraction of blood proteins might harm their bodies in the long turn'. In Poverty by America, Matthew Desmond describes that the United States, the richest country of the world, has more poverty than any other advanced democracy [19]. And that US policies privilege the affluent more than the poor. In that book, he also mentions paid plasma donation as a way to get income, but that in a particular case it does not work as 'She tried donating plasma, but her veins were too small'. Sandel and Desmond are in the paid–unpaid discussion not in favour of the ethical–market arguments for paid donations but favour the ethical–societal arguments for more solidarity and equity. On 18 July 2023, the ENVI Committee of the EU Parliament confirmed that blood donation in Europe is based on the principle of voluntary and unpaid donation and that compensation, even in countries where it is permitted, should not be used as an incentive to recruit donors or lead to the exploitation of vulnerable people. They also wanted strict rules on advertising around SoHO donations, which should prohibit any references to financial rewards. This is in sharp contrast with daily practice in the United States nowadays, where websites of plasma collection centres already at entrance mention that you can earn up to $6000 per year [20]. As authors of this article, we still and without hesitation are in favour of VNRDs—Alice because she has been a plasma donor since the age of 18 and has first-hand experience of the value of systems based on the ethical value of voluntary, unpaid donation and the essential role that donor organizations can play in creating a community of regular, motivated donors. The promotion of these values in all countries of the world is indeed one of the main objectives of the International Federation of Blood Donor Organizations (IFBDO/FIODS), of which she is a member of the Executive Council and head of the European Continental Committee [21]. Cees is in favour of VNRDs because he had already warned in 1979 about the risks of the paid donor system and because he is a long-term survivor of HIV and HCV, which he got being a haemophiliac [22]. He believes strongly that we have a moral legacy towards all who suffered from these blood-related viral infections to strive for a safe and healthy environment for donors as well as recipients of blood and PDMPs. We propose a series of actions that the EU Member States and relevant stakeholders (blood collections services, donor organizations, patient groups, EU Commission, EU Member States, public health authorities, sector associations, etc.) can adopt to realize the requested increase of blood and plasma donations and group and number them 1 to 10 according to the levels of responsibility. At the moment, the organization and responsibility for collecting blood and plasma in the EU Member States varies widely, so the need for a strong EU coordination effort is crucial. Once the new SoHO regulation is adopted, it seems logical that the new SoHO Coordination Board at the EU level together with the new SoHO National Authorities in the EU Member States should further explore what actions are needed in the different EU Member States but with the final aim to reach EU self-sufficiency. We have calculated that the EU needs at least 2 million extra donors of blood and plasma. Of course, this calculation has its limitations. There are no accurate or actual data of demand and supply of blood components and PDMPs as far as we know on which we can make a more accurate analysis. Or data are lagging behind as with the data collected by the EDQM, which goes back to 2017–2019 before the COVID-19 pandemic [25]. Data on PDMPs are more in the private domain. Information is also missing on plasma collected in the four EU countries with paid donations; nor is information available whether this collected plasma is returning also to these countries once processed to PDMPs. Collecting more accurate data in the future on the collection and use of blood and blood components and PDMPs is one of the challenges for the to-be-established single SoHO National Authority in the EU Member States and the SoHO Coordination Board at the EU level. Another limitation of this article is the reality level of the proposed EU SoHO Regulation. It is quite an ideal for the EU to become less dependent on US plasma in a situation where this has not proven to become a reality in the past 50 years. Or even worse, the EU has in these 50 years become more and more dependent on the use of US plasma from paid donations. But the COVID-19 pandemic and the possibility that the former US President Donald Trump wanted to make use of the 'US Defense Act' to limit the export of US plasma to non-US countries made EU policy makers once more realize their strategic dependence on the United States for PDMPs. So, there is a huge challenge for the EU ahead to realize this concept of independence from US plasma and to replace it by enough plasma from NRVD donations from EU blood and plasma donors. The issue is also complicated because the EU continues with a regulatory situation where blood and blood components are in the jurisdiction of the new SoHO regulation whereas the PDMPs are part of the EU Pharmaceutical Legislation. In the end, however, one of the main messages we would like to convey is that to claim that it is necessary to pay—for the achievement of self-sufficiency in blood and PDMPs at the European level—for the donation of blood or plasma constitutes a short-sighted way of dealing with the challenge of our independence from supplies coming from the United States. And the reason is that, on one hand, we know that our donors are ready to donate plasma if they are well informed and if they have the opportunity to make this act a positive experience, in public and well-organized collection centres. On the other hand, relying on public collection systems that operate on the basis of a counter-processing regime represents the most appropriate way to protect our community as a whole, which keeps both those who donate and those who need blood-derived medicines safe from exploitation and market fluctuations. Europe is showing its engagement in this regard, and we count on our contribution as donors and patients to help achieve our common goals. With the almost unanimously adopted amendments in the ENVI Committee of the European Parliament of the new EU SoHO Regulation, the challenge is how the EU can become less dependent on US plasma. Currently, the EU is almost 40% dependent on PDMPs from paid donations. The ENVI Committee has sharpened the rules for donation and insisted that EU countries could allow compensation or reimbursement for losses or expenses related to their donations. Compensation should not be used as an incentive to recruit donors, nor should it lead to the exploitation of vulnerable people. They also want strict rules on advertising around SoHO donations, which should prohibit any references to financial rewards. To become independent of the United States for plasma donations implies a big challenge for the EU. In this article, we have formulated a number of actions for all stakeholders to reach this goal; we have calculated that Europe needs at least 2 million extra blood and plasma donors who are willing to donate their blood and/or their plasma several times a year. Furthermore, we explored the possibilities of a closer cooperation between Blood Collection Services and patient and donor organizations. Finally, only a combined action plan of all EU Member States together with the European Commission can lead to a lesser or no degree of dependence on US plasma from paid donations. We are grateful to Dr. Paul Strengers (consultant) for his notes on a previous version of this article and his assistance with the calculation in Box 2 and Dr. Annemarie de Knecht-van Eekelen (medical historian) for the editing of this manuscript. C.S. wrote the first draft of the manuscript and A.S. reviewed and finalized the manuscript. The authors declare no conflicts of interest. The authors received no specific funding for this work. The data that support the findings of this study are available in Ref. 9. These data were derived from the following resources available in the public domain: Ref. 9. There are no data in the publication.