Lਅਔਔਅ ਔਏ ਔਈਅ Eਉਔਏ Transfusion and ecology: sense, nonsense, or missense? Olivier Garraud1,2, Jean-Daniel Tissot3 1
National Institute of Blood Transfusion, Paris, France; 2EA3064, Faculty of Medicine, University of Lyon, SaintEtienne, France; 3Interregional Transfusion Centre, d'Epalinges Site, Epalinges, Switzerland
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anticoagulant, led to little waste. Nowadays, however, "simple" processing of whole blood or fractions requires several plastic bags in addition to needles, sterile connector blades, and tubing for one final bag of a blood component. This process generates an enormous amount of waste to be incinerated for safety reasons, and significant pollution... 3) There must be no harm to donors, especially regarding iron store depletion. Infrequent donation of whole blood has a limited impact on donors' iron stores but double red blood cell donation carries a higher risk of iron depletion. Iron stores and ferritin levels are affected. Iron stores are typically replaced by a normal diet, although donors are requested to refrain from donating too often; indeed, frequent donations may lead to unacceptable iron depletion in some female donors. However, iron replacement (oral iron intake, especially for female donors) is far from universal, and is still debated. 4) There must be evaluable benefit for the recipient. Clinically unjustified transfusions as well as transfusions for non-medical reasons (e.g. doping) must be prohibited. Blood transfusions should provide elements that are lacking, and this is per se ecologically sound as long as there is no excess. Recently, a new concept has emerged: "Patient Blood Management". This takes into account all elements that should be in place, enabling the use of blood components to be minimised. Any unnecessary blood sampling for repeated and non-informative laboratory testing ("medical vampirism") must be strictly avoided. Every effort must be made to maximise the therapeutic value of a transfused blood component: compatibility should be optimised, the storage duration should be minimised, and blood components must not be exposed to unnecessary manipulation which could aggravate the storage lesion. An evaluation of risk-benefit ratios is not always simple. For example, pathogen reduction/ inactivation technology provides both benefits (e.g. reduction of infectious risk, decrease in alloimmunisation and mitigation of graft-versus-host reactions) and negative effects (e.g. weakening of cells, generation of extra bags and waste).
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Dear Sir, As representatives of over 200 countries recently gathered in Paris to discuss the climate change and world ecology (COP21), we propose looking at transfusion medicine in the context of ecology. Blood transfusion is possible, but not "natural"; it cannot be considered "ecological" because it distorts major laws of nature. However, can transfusion follow ecological rules, even if only partially? There is no uniform definition of ecology, as it is affected by its understanding by scientific, political, humanistic (...) communities. Indeed, ecology appears to be "a concept". Applied to transfusion, there should be no intentional harm to natural elements and, if such harm is inflicted despite precautions, it should be possible to neutralise it by natural means ("First, do no harm"). The concept also implies that humans act in a natural environment, either consolidating or weakening it. On this background we identified five key points to be considered: 1) The impact of transfused blood components on DNA/RNA-based materials. Two issues need to be considered. Firstly, red blood cell, plasma, or platelet products for transfusion may contain some residual leucocytes, including circulating stem cells. Such cells may create micro-chimerism in the recipient, although at a limited level because of stringent leucoreduction of blood components 1. To prevent this risk in immunosuppressed patients and in intra-family situations, a blood component can be subjected to either irradiation or pathogen reduction/inactivation technology, but at the expense of the use of gammaor X-rays or chemicals2. Secondly, although this has not been reported, it cannot be completely excluded that endogenous -non-pathogenic- viruses from donors recombine with closely related viruses in the recipients, with unknown long-term consequences. Here again, pathogen reduction/inactivation technology would lower this risk. It also remains to be established whether blood transfusion can induce epigenetic modifications in the recipients' DNA which could be transmitted to the patients' offspring. 2) Generation of compensated vs non-compensated waste. Direct arm-to-arm transfusion, with blood components kept in reusable glass bottles with
Blood Transfus 2017; 15: 274-5 DOI 10.2450/2016.0014-16 274
All rights reserved - For personal use only No other use without premission
© SIMTI Servizi Srl
Transfusion and ecology
Acknowledgements The Authors very warmly thank Prof. Zbigniew M. Szczepiorkowski (Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA) for critical advice on this manuscript and help in its editing. They also acknowledge their long-time colleagues for inspiration and fruitful discussion and dedicate this essay to the memory of Prof. Jean-Jacques Lefrère (University Paris-Descartes, France) who died earlier last year. The Authors declare no conflicts of interest.
References
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Simancas-Racines D, Osorio D, Martí-Carvajal AJ, ArevaloRodriguez I. Leukoreduction for the prevention of adverse reactions from allogeneic blood transfusion. Cochrane Database Syst Rev 2015; 12: CD009745. Heddle NM, Lane SJ, Sholapur N, et al. Implementation and public acceptability: lessons from food irradiation and how they might apply to pathogen reduction in blood products. Vox Sang 2014; 107: 50-9. Custer B, Janssen MP; Alliance of Blood Operators RiskBased Decision-Making (RBDM) Initiative. Health economics and outcomes methods in risk-based decision-making for blood safety. Transfusion 2015; 55: 2039-47. Mou H. The political economy of the public-private mix in heath expenditure: an empirical review of thirteen OECD countries. Health Policy 2013; 113: 270-83. Fiore RN, Goodman KW. Precision medicine ethics: selected issues and developments in next-generation sequencing, clinical oncology, and ethics. Curr Opin Oncol 2016; 28: 83-7.
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5) The transfusion process must be acceptable to taxpayers who represent "the society". Blood component production and transfusion medicine are expensive3. In most high-income countries, expensive health care is not charged directly to the patient but rather spread across the majority of citizens, through direct and/or indirect taxes. Thus, the principal stakeholders are members of the society, whether they aware of this or not. An important issue is how much wealthy countries can dedicate to global health expenditure4. Subsidiarity and solidarity are far from being the rule everywhere in the world, especially in low-income countries. An absence of so-called "health democracy", with its multiple causes, is not "ecology". It can be hoped that the transfusion process will benefit from a renewed awareness that the welfare of humanity parallels the welfare of Nature. Ecology is a holistic concept and we must advocate it, because it encompasses health issues and humanities. In high-income countries, transfusion safety has benefited from multiple layers of measures (almost always added, and very rarely removed), but each is extremely expensive: what are or should be the common-sense levels of transfusion-induced costs and process economy? Historically, the field of transfusion medicine had to face one major challenge, which was to meet the demand (a quantitative issue); today we need to focus on qualitative issues, as the majority of multi-transfused recipients benefit from transfusion programmes that provide components that are matched for increasing numbers of antigens. However, while "health democracy" exacts that every patient receives the "best" possible blood component, it does not imply that the "best" component is the same for everyone. Modern transfusion medicine -which now stands for precision medicine5- no longer recommends the "one fits all" policy that was imposed during the last two decades by (or on) blood establishments to improve global quality and safety. Not all patients would benefit from blood components tested for new variant Creutzfeldt-Jakob disease (when available) because many would not survive long enough to develop the disease. This consideration would enable better management of donors, limiting unnecessary deferrals, which is especially important when resources are scarce such as in certain blood groups. One can appreciate that this is precisely "ecological" vocabulary.
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5)
Arrived: 20 January 2016 - Revision accepted: 2 March 2016 Correspondence: Olivier Garraud INTS 6, rue Alexandre Cabanel 75015 Paris, France e-mail: [email protected]
Blood Transfus 2017; 15: 274-5 DOI 10.2450/2016.0014-16 All rights reserved - For personal use only No other use without premission
275
National Institute of Blood Transfusion, Paris, France; 2EA3064, Faculty of Medicine, University of Lyon, SaintEtienne, France; 3Interregional Transfusion Centre, d'Epalinges Site, Epalinges, Switzerland
zi
Sr l
anticoagulant, led to little waste. Nowadays, however, "simple" processing of whole blood or fractions requires several plastic bags in addition to needles, sterile connector blades, and tubing for one final bag of a blood component. This process generates an enormous amount of waste to be incinerated for safety reasons, and significant pollution... 3) There must be no harm to donors, especially regarding iron store depletion. Infrequent donation of whole blood has a limited impact on donors' iron stores but double red blood cell donation carries a higher risk of iron depletion. Iron stores and ferritin levels are affected. Iron stores are typically replaced by a normal diet, although donors are requested to refrain from donating too often; indeed, frequent donations may lead to unacceptable iron depletion in some female donors. However, iron replacement (oral iron intake, especially for female donors) is far from universal, and is still debated. 4) There must be evaluable benefit for the recipient. Clinically unjustified transfusions as well as transfusions for non-medical reasons (e.g. doping) must be prohibited. Blood transfusions should provide elements that are lacking, and this is per se ecologically sound as long as there is no excess. Recently, a new concept has emerged: "Patient Blood Management". This takes into account all elements that should be in place, enabling the use of blood components to be minimised. Any unnecessary blood sampling for repeated and non-informative laboratory testing ("medical vampirism") must be strictly avoided. Every effort must be made to maximise the therapeutic value of a transfused blood component: compatibility should be optimised, the storage duration should be minimised, and blood components must not be exposed to unnecessary manipulation which could aggravate the storage lesion. An evaluation of risk-benefit ratios is not always simple. For example, pathogen reduction/ inactivation technology provides both benefits (e.g. reduction of infectious risk, decrease in alloimmunisation and mitigation of graft-versus-host reactions) and negative effects (e.g. weakening of cells, generation of extra bags and waste).
©
SI M
TI
Se rv i
Dear Sir, As representatives of over 200 countries recently gathered in Paris to discuss the climate change and world ecology (COP21), we propose looking at transfusion medicine in the context of ecology. Blood transfusion is possible, but not "natural"; it cannot be considered "ecological" because it distorts major laws of nature. However, can transfusion follow ecological rules, even if only partially? There is no uniform definition of ecology, as it is affected by its understanding by scientific, political, humanistic (...) communities. Indeed, ecology appears to be "a concept". Applied to transfusion, there should be no intentional harm to natural elements and, if such harm is inflicted despite precautions, it should be possible to neutralise it by natural means ("First, do no harm"). The concept also implies that humans act in a natural environment, either consolidating or weakening it. On this background we identified five key points to be considered: 1) The impact of transfused blood components on DNA/RNA-based materials. Two issues need to be considered. Firstly, red blood cell, plasma, or platelet products for transfusion may contain some residual leucocytes, including circulating stem cells. Such cells may create micro-chimerism in the recipient, although at a limited level because of stringent leucoreduction of blood components 1. To prevent this risk in immunosuppressed patients and in intra-family situations, a blood component can be subjected to either irradiation or pathogen reduction/inactivation technology, but at the expense of the use of gammaor X-rays or chemicals2. Secondly, although this has not been reported, it cannot be completely excluded that endogenous -non-pathogenic- viruses from donors recombine with closely related viruses in the recipients, with unknown long-term consequences. Here again, pathogen reduction/inactivation technology would lower this risk. It also remains to be established whether blood transfusion can induce epigenetic modifications in the recipients' DNA which could be transmitted to the patients' offspring. 2) Generation of compensated vs non-compensated waste. Direct arm-to-arm transfusion, with blood components kept in reusable glass bottles with
Blood Transfus 2017; 15: 274-5 DOI 10.2450/2016.0014-16 274
All rights reserved - For personal use only No other use without premission
© SIMTI Servizi Srl
Transfusion and ecology
Acknowledgements The Authors very warmly thank Prof. Zbigniew M. Szczepiorkowski (Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA) for critical advice on this manuscript and help in its editing. They also acknowledge their long-time colleagues for inspiration and fruitful discussion and dedicate this essay to the memory of Prof. Jean-Jacques Lefrère (University Paris-Descartes, France) who died earlier last year. The Authors declare no conflicts of interest.
References
3)
4)
Sr l
2)
Simancas-Racines D, Osorio D, Martí-Carvajal AJ, ArevaloRodriguez I. Leukoreduction for the prevention of adverse reactions from allogeneic blood transfusion. Cochrane Database Syst Rev 2015; 12: CD009745. Heddle NM, Lane SJ, Sholapur N, et al. Implementation and public acceptability: lessons from food irradiation and how they might apply to pathogen reduction in blood products. Vox Sang 2014; 107: 50-9. Custer B, Janssen MP; Alliance of Blood Operators RiskBased Decision-Making (RBDM) Initiative. Health economics and outcomes methods in risk-based decision-making for blood safety. Transfusion 2015; 55: 2039-47. Mou H. The political economy of the public-private mix in heath expenditure: an empirical review of thirteen OECD countries. Health Policy 2013; 113: 270-83. Fiore RN, Goodman KW. Precision medicine ethics: selected issues and developments in next-generation sequencing, clinical oncology, and ethics. Curr Opin Oncol 2016; 28: 83-7.
zi
1)
Se rv i
5) The transfusion process must be acceptable to taxpayers who represent "the society". Blood component production and transfusion medicine are expensive3. In most high-income countries, expensive health care is not charged directly to the patient but rather spread across the majority of citizens, through direct and/or indirect taxes. Thus, the principal stakeholders are members of the society, whether they aware of this or not. An important issue is how much wealthy countries can dedicate to global health expenditure4. Subsidiarity and solidarity are far from being the rule everywhere in the world, especially in low-income countries. An absence of so-called "health democracy", with its multiple causes, is not "ecology". It can be hoped that the transfusion process will benefit from a renewed awareness that the welfare of humanity parallels the welfare of Nature. Ecology is a holistic concept and we must advocate it, because it encompasses health issues and humanities. In high-income countries, transfusion safety has benefited from multiple layers of measures (almost always added, and very rarely removed), but each is extremely expensive: what are or should be the common-sense levels of transfusion-induced costs and process economy? Historically, the field of transfusion medicine had to face one major challenge, which was to meet the demand (a quantitative issue); today we need to focus on qualitative issues, as the majority of multi-transfused recipients benefit from transfusion programmes that provide components that are matched for increasing numbers of antigens. However, while "health democracy" exacts that every patient receives the "best" possible blood component, it does not imply that the "best" component is the same for everyone. Modern transfusion medicine -which now stands for precision medicine5- no longer recommends the "one fits all" policy that was imposed during the last two decades by (or on) blood establishments to improve global quality and safety. Not all patients would benefit from blood components tested for new variant Creutzfeldt-Jakob disease (when available) because many would not survive long enough to develop the disease. This consideration would enable better management of donors, limiting unnecessary deferrals, which is especially important when resources are scarce such as in certain blood groups. One can appreciate that this is precisely "ecological" vocabulary.
©
SI M
TI
5)
Arrived: 20 January 2016 - Revision accepted: 2 March 2016 Correspondence: Olivier Garraud INTS 6, rue Alexandre Cabanel 75015 Paris, France e-mail: [email protected]
Blood Transfus 2017; 15: 274-5 DOI 10.2450/2016.0014-16 All rights reserved - For personal use only No other use without premission
275
