Falsification or paradigm shift? - Wiley Online Library

AWA R D S L E C T U R E Falsification or paradigm shift? Toward a revision of the common sense of transfusion _2817

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Albert Farrugia

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ransfusion started with the dramatic clinical observations of Blundell, but could not be exploited for many years because of immunologic barriers. Discoveries including blood groups and blood preservation, usually fueled by war, resulted in the establishment of banked blood transfusion for blood loss and medical anemia. Storage in plastic bags, again prompted by the needs of war, ultimately allowed the sterile separation of blood components, initially restricted to plasma and red blood cells (RBCs) for normovolemic anemia. The development of cryoprecipitate for hemophilia A provided a widespread driver for the separation of plasma and the use of RBCs in lieu of blood for most transfusions. In the current era, whole blood as a therapeutic modality has become virtually extinct, and the universal use of stored RBCs has started to come under scrutiny as a result of possible adverse events. Concurrently with these developments, transfusion has shifted to a “product” paradigm, as defined by Thomas Kuhn, focused on maximizing donation, inventory, and supply. This work assesses the tensions developing within the product paradigm and proposes that it is falsified, or demarcated as described by Karl Popper, by a new “patient” paradigm focusing on blood as a modality and patients as the focus of transfusion medicine.

From the Centre for Orthopaedic Research, Department of Surgery, Faculty of Medicine and Surgery, University of Western Australia, WA, Australia. Address reprint requests to: Albert Farrugia, PhD, Centre for Orthopaedic Research, Department of Surgery, Faculty of Medicine and Surgery, University of Western Australia, WA, Australia; e-mail: [email protected]. This paper is based on an oration given on the occasion of the award of the Ruth Sanger Oration to the author by the Australia and New Zealand Society for Blood Transfusion on October 20, 2009, in Adelaide, South Australia Received for publication June 10, 2010; accepted June 10, 2010. doi: 10.1111/j.1537-2995.2010.02817.x TRANSFUSION 2011;51:216-224. 216 TRANSFUSION

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THE DEVELOPMENT OF SCIENTIFIC THINKING: COMPETING OR COMPLEMENTARY FRAMEWORKS In many popular depictions of scientific thinking, including media-driven statements by working scientists, the image of knowledge by “accrual” is proposed. In this image, the inexorable march of human progress leads to increased knowledge through assiduous application of logic and systematic investigation by experiment. This so-called “scientific method” is an example of the general concept of induction, whereby an apparent human need for order and regularity imposes the development of universal frameworks from the result of individual observations. This example of inductive philosophy views “objective” facts as the primary input to science. In this viewpoint, theory is viewed as the synthesis and generalization of such factual information. Most modern philosophers and psychologists would consider this credo as untenable. All observation is influenced by theory that imposes an expectation on how data are gathered and interpreted. Theory, also, does not develop as a simple and logical consequence of observation and does not arise from a systematic accrual of facts. Norwood Russell Hanson proposed that observation is theory-laden, with the languages of theory and observation being deeply interwoven. He characterized “pure” observation as a myth, claiming that “In any observation . . . the cloven footprint of theory can readily be detected.”1 In 1961, Thomas Kuhn, building on Hanson’s work, proposed another way of looking at scientific theories. In a far-reaching and influential essay, he developed the concept that scientific thinking is reflected, at any point in time, in a set of accepted and shared beliefs, which he called a paradigm.2 Kuhn proposed that scientific thinking goes through long periods of stable, unquestioning, periods, which he designated as “normal science,” punctuated by paradigm shifts. During such shifts, the current, dominant, paradigm is brought under increasing pressure as a result of anomalies that violate its expectations, until it is replaced by another paradigm through what Kuhn claimed is no less than a scientific revolution. Kuhn’s critique of the accrual concept of scientific knowledge drew on examples to contend that theories of the past were no

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more or less valid, in the context of their time, than the theories that eventually replaced them, through paradigm shifts, down to our present time. His examples included the progression of cosmologic theory through Ptolemaic, Copernican, Newtonian, and Einsteinian models. Kuhn discusses how initially unrelated factors such as experimental hardware can influence paradigm shifts, exemplified by the crucial role that the development of air pumps in the 18th century had on the overthrow of the phlogiston theory of combustion through Lavoisier’s work on oxygen. Kuhn, building on Hanson, emphasized that since no scientist works independently of theory, all experimental work is done and interpreted within the disciplinary matrix of the prevalent paradigm. He commented that, once adopted as a paradigm, no theory is recognized as being testable by any quantitative tests it has not already passed.3 Hanson’s and Kuhn’s work on scientific thinking is lineagely descended from David Hume’s critique of the inductive interpretation of the explosion of scientific observations made in the 17th and 18th centuries, as a result of which a large number of previously concealed regularities in nature had been brought to light. This notion led to the rapid proposal that such observations could be used to build general overarching frameworks that would explain all phenomena. Hume observed that this universality could not be justified, as a multitude of observations may serve to support a framework, but only one observation may prove it wrong.4 Karl Popper sought to address the problem of induction through asserting that science was deductive in essence. Popper developed the concept of falsifiability,5 whereby an observation, while not having the power to prove a theory, could be used to show that a theory is false. He conceived of science as a problem solving exercise through testable theories, with falsifiability being the criterion for testability of scientific theories and for credentialing a theory as scientific by demarcating it from non(pseudo)scientific theories. Popper saw scientific theories ensuing through a selection process with falsifiability providing the selector to sort out the best theory, analogous to natural selection in evolution. As such, for Popper scientific thinking and theory building is inherently dynamic and continuous, a process of constant and critical debate within the scientific community. Kuhn, on the other hand, held that scientific development is characterized by long periods of relative stasis, during which adherents of the current paradigm practice normal science by elaboration, revision, and refinement of the accepted paradigm through experiment and measurement. As such, Kuhn and Popper had different views; Kuhn’s “great leaps forward” apparently in tension with Popper’s falsifiability-driven continuous and deductive progression, and they debated these differences strongly.6 A synthesis of their approaches is feasible.

Kuhn came to recognize that while a paradigm common to all members of the relevant professional community is a necessary condition for science, it is not a sufficient one. Non(pseudo)scientific ideologic constructs such as Marxism and Freudianism are also paradigms but, as discussed by Popper,7 cannot be falsified as any potential anomaly can be fitted into them. Scientific paradigms are distinguished in that the hypotheses generated are amenable to falsification. Taking Popper’s selection concept to this debate, I propose that Eldridge and Gould’s8 theory of punctuated equilibria is analogous to Kuhn’s paradigm progression, while Popper’s view is closer to the phylectic gradualism which Eldridge and Gould contest. Irrespective of which theory best addressed speciation, the presence of a selective pressure is required; in scientific thinking, this pressure is provided by falsifiability as a demarcation criterion.

FALSIFICATION OF PARADIGMS: RELEVANCE TO THE BIOLOGIC SCIENCES? Much of the concepts outlined so far have arisen from pondering the physical sciences; Kuhn was himself a theoretical physicist by discipline, while Popper taught mathematics and physical science through qualifying with a thesis on geometry. Thus most of the examples drawn were from physics and chemistry, and doubts on the applicability of Popper’s falsifiability to biology,9 while rebuffed,10 have led to the proposal that biology has no laws of its own and is not subject to falsifiability.11 Popper contributed to some of these doubts by asserting initially that evolution, one of the major theories of biologic science, is not a theory as much as a “metaphysical research program,”12 a statement that continues to give the creationists joy,13 despite Popper’s subsequent recantation.14 Many eminent biologic scientists have concurred with the ideas of Kuhn and Popper. Charles Darwin reflected on the primacy of theory when he wrote to Henry Fawcett:15 “How odd it is that anyone should not see that all observation must be for or against some view if it is to be of any service,” thus refuting, consciously or unconsciously, the very inductivist tenet that he embraced in his autobiography when he claimed that he “worked on true Baconian principles, and without any theory collected facts on a wholesale scale.”16 This interesting dichotomy between the inductive and deductive tendencies is very typical of the way many scientists view their activity. Nobel Prize winners Peter Medawar (prize for medicine or physiology 1960) and John Eccles (prize for medicine or physiology 1963) were both enthusiastic “Popperians.” Medawar considered that “innocent, unbiased observation is a myth”17 and commented on the “state of dignified, yet utter, confusion” enveloping the lay public in their Volume 51, January 2011

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Fig. 1. Synthesis of Kuhnian and Popperian hypotheticodeductivism in scientific thinking.

ideas of what constitutes scientific inquiry18 while discussing the irrelevance of the scientific method. Commenting on his attraction to the theory of enformed systems in his development of a scientific theory of the self, Eccles stated that “Induction was shown to be untenable as a scientific method by Popper . . . advances in scientific understanding come ideally from hypotheticodeductivism: firstly, development of a hypothesis in relation to a problem situation, and secondly, its testing in relation to all relevant knowledge and furthermore by its great explanatory power.”19No more elegant summary of Popper’s ideas exists. It seems to this author that questions as to whether the epistemologic proposals described so far apply to the biologic sciences in general and to transfusion medicine in particular are best addressed through extracting the core underpinnings of these proposals (Fig. 1). Whether the dynamism proposed by Kuhn and Popper is sporadic or continuous, respectively, scientific advancement is through such dynamism, fueled by curiosity and critical thinking. It seems to this author that such concepts are as useful to the biologic sciences as to other disciplines.

THE PARADIGM IN TRANSFUSION MEDICINE Kuhn’s thinking is embedded in everyday practice and transfusion medicine is no exception. The recent transfusion literature is peppered with allusions to “paradigm,” including several of the presentations given at recent meetings.20,21 Most of these allusions allude to the established thinking—the “common sense”—of the field. Transfusionists including Blajchman and Klein,22 Isbister,23 and Blumberg and Heal24 have invoked Kuhn and have analyzed the field in terms of their view of the underlying paradigm and any developing tensions. In 1995, Blumberg and Heal24 proposed that the succession of transfusion paradigms involved the shifts to safer therapy as a result of, first, the understanding of blood groups and, subsequently, the recognition and avoidance 218 TRANSFUSION


Fig. 2. The current transfusion paradigm.

of viral transmission. Blajchman and Klein22 agreed and further analyzed the establishment of the current multilayered precautionary safety framework. Both these studies perceived further paradigm shifts through safety developments, by addressing transfusion-induced modulation and introducing pathogen reduction, respectively. Somewhat more resonant to Kuhn’s actual concepts, Isbister23 proposed that the transfusion paradigm was primarily donor-related through a supply-based— “how and how much”—philosophy. Isbister proposed a new paradigm—“recipient orientated”—focusing on the medical oversight of the patient. This concept is further described as a proposed new paradigm by Thomson and coworkers.20 All these eminent authorities have drawn attention to Kuhn’s recognition that the progression to a new paradigm can be slow and fraught with tension and that a candidate new paradigm must solve problems precipitated through the old paradigm, while being sufficiently unprecedented to generate its own cadre of proponents.

THE COMMON SENSE OF TRANSFUSION MEDICINE The multicomponent paradigm that currently constitutes common sense or normal transfusion medicine is summarized in Fig. 2. Theory precedes practice, and the tenets of the current paradigm are preembedded in many normal practitioners of transfusion before any actual involvement in the field, mostly through the cursory overview of the field afforded through most of medical education, particularly standard texts. (For a discussion on how textbooks shape science while being detached from its reality see Kuhn.3) By “common sense” is meant the assumptions that underlie transfusion practice in all its aspects in the “inexpert” policy, public, and medical environments that actually deliver most of the decision making and the actual therapy. Some of these individual elements will be assessed.


THE PRODUCT PARADIGM AND THE DEMISE OF BLOOD TRANSFUSION Centralized blood services, through which most of transfusion therapy is delivered in the current paradigm, partly calibrate their performance by the amount of blood that they process to components. The more this approaches 100%, the better. Yet, “twas not always Fig. 3. The UK blood service replaces bottles with bags. On http://www.blood.co.uk/ thus.” The technical perquisite for the about-blood/history/. manufacture of blood components in the blood bank was the invention of the FVIII became the fractionation driver as Pool’s technique plastic bag in 1950. The factors behind this development was rapidly adapted t to large-scale manufacture.31 The did not include the fractionation of blood; the need for a sterile container that was flexible and would allow potential for generating FVIII for hemophilia care was recpressure-assisted rapid transfusion to Korean War casualognized and stimulated a swing from bottles to bags for ties underpinned this invention.25 Plasma was the only collection.29 The UK blood service specifies 1975 as the component harvested from blood at this time, through period when this movement was under way, stimulated by gravity sedimentation into satellite packs. The developthe need for components (Fig. 3). Clearly, this shift to ment of the refrigerated centrifuge in 1954 allowed the components was dependent on the development of the separation of plasma soon after collection, allowing the plastic bag. The other component that made its appearpreservation of the labile coagulation factors, something ance at this time was the platelet (PLT) concentrate, folthat was not immediately appreciated or applied. Devellowing Scott Murphy’s work demonstrating viability of opments in the understanding of the labile nature of antiPLTs harvested and stored in plastic bags.32 Murphy hemophilic factor (FVIII) led to the use of fresh or freshly pointed out the importance of maintaining access to FVIII frozen plasma to treat hemophilia A and subsequently its in the possible routes to PLT concentrate manufacture.32 use as a raw material for the manufacture of the first FVIII The need to extract FVIII from the maximum possible concentrate, a crude modification of Cohn Fraction I.26 number of donations provided a strong driver to the current paradigm and to the quasi-extinction of the transThe real breakthrough in the treatment of hemophilia A fusion of whole blood. came when Judith Pool published her findings on cryoThe resultant fissure between the supply-driven precipitate in Nature27 and the New England Journal of blood bank community and the clinical community of Medicine.28 Pool showed that this component could be blood prescribers has long been felt: manufactured in a closed two-bag system by any blood bank possessing basic separation and freezing facilities, The constant argument that red cell concentrates allowing the RBCs to be reconstituted with the residual should be used in order to ensure adequate Factor plasma, which could also be separately harvested into a VIII supplies for persons with haemophilia may third bag.29 Pool’s observations were, as she explained appear valid reasoning on the surface, but it is a rather herself, entirely fortuitous, although her achievement in negative form of education. Thus, it is not surprising exploiting them cannot be understated. Cryoprecipitate that clinicians who are patient-orientated have not and its use to treat hemophilia A had actually been been receptive to blood transfusion education that described 9 years before Pool’s papers;30 clearly publicaclearly has been motivated by the needs of the transtion in well-known English journals was needed fusion service rather than by the needs of the particuto ensure the widespread adoption of this crucial lar patient, whether the transfusion logic was correct development. or not.”23 The development of cryoprecipitate was as crucial in developing the current paradigm as it was for the treatIsbister’s comments reflect the underlying and conment of hemophilia. The ability to deliver effective treatstant tension that has always accompanied the blood ment of a previously quasi-lethal condition through a transfusion to blood component therapy shift. In 1976, blood bank product threw the blood bank sector firmly on Grindon wrote: the road to being plasma producers. At this time albumin was the main product of plasma fractionation, and suffiToday, the only remaining legitimate indication for cient raw material was generated from paid source plasma the transfusion of whole blood is acute blood loss. and residual plasma from separated and expired blood. Many transfusion therapists have even advocated Volume 51, January 2011

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giving one third to one half of all transfusions in the operating room as PRBC. Such practice has been shown to be not only possible but successful if combined when necessary with salt solution or plasma protein fraction.”33 [my underlines] One wonders how Dr Grindon and his contemporaries would view today’s landscape, where, in most “developed” blood systems, less than 5% of transfusions are delivered as whole blood. The advocates of the current paradigm contend that the tenet “components are as good as blood” to be uncontestable. Versions of the statement “When absolutely required, whole blood may be synthesized from packed red cells and fresh frozen plasma, supplemented by platelet concentrates as necessary”34 pepper the textbook and peer literature and have become embedded as common sense. The physiologic reality of the composition of blood underpins and predicates the paradigm. While “giving the patient what he/she needs” is convincing when addressing normovolemic anemia and thrombocytopenia, the universal validity has always been questionable and is now under increased pressure. To assess its validity, knowledge of the epidemiology of transfusion is needed. Surveys in Britain,35 the United States,36 and France37 indicate that routine surgical intervention, presumably for blood loss, accounts for approximately half of RBC transfusions. The issue is whether this clinical population is best served by transfusion with stored, plasma-depleted RBCs.

suggested that a trade-off for the increased testing costs was possible through the extension of the shelf life, despite the decreased recovery and half-life of the resulting PLTs.40 Similarly, the question of supplementation of RBCs with hemostatic components in situations of blood loss has been widely investigated. Counts and colleagues41 concluded that massively transfused patients given PLT and cryoprecipitate-depleted whole blood did not require additional whole blood or fresh-frozen plasma (FFP). Coagulation Factors V and VIII, long considered to be specifically enriched in FFP, were depleted in the blood transfused by Counts and coworkers but patient levels were not correlated with the number of units transfused. Notably, the residual plasma in these units contained 25% of the initial fibrinogen, which was shown by Hiippala and coworkers42 to be the critical hemostatic factor in patients undergoing surgery, a finding confirmed for trauma patients.43 Despite a significantly lower blood replacement than studied by Counts and coworkers supplementation with FFP was required to ensure adequate fibrinogen. In the 16 years between the two studies, automated component separation systems stripped RBCs of all but a minute residue of the residual plasma, explaining the need for supplementation. Plasma depletion is also a feature of current PLT manufacture where synthetic media replace much of the plasma, so any required coagulation supplementation from this source is also minimized.

THE PLIGHT OF TRAUMA PATIENTS STORAGE AND TRANSFUSION OF COMPONENTS The ongoing debate on the possible adverse effects of stored RBCs (summarized in Steiner and Stowell38) shows that this issue is unsettled and requires more systematic investigation in the form of randomized clinical trials. The application of precautionism to this issue would demand action, given the difficulty in performing such trials39 and the possible seriousness of the events involved. Criteria for RBC storage specify an expiry date based on a requirement of a survival rate of 75% of the transfused RBCs after 24 hours, a quality criterion that appears modest and on the basis of which increasingly prolonged storage periods, in conformance with the inventory requirements, have been allowed. The RBC storage lesion is well characterized in vitro, and the lack of immediate oxygen delivery as a result of 2,3-diphosphoglycerate is frequently dismissed by the current paradigm supporters because of its correction over the first 3 days after transfusion. This acceptance of inferior recovery and efficacy on the basis of the maintenance of inventory would not be given credence in most areas of therapeutic practice. The primacy of the “inventory first” paradigm is also reflected in the recent debate around PLT concentrate bacterial testing, where it was 220 TRANSFUSION


The limitations of the current paradigm impose particular consequences on the patient who is massively transfused because of trauma. Studies indicate that a higher ratio of plasma to RBCs, best approaching 1:1, is associated with decreased mortality.44 There are logistical difficulties in delivering thawed FFP in acute situations,45 and some paradigm-bound centralized blood services have addressed this by extending the shelf life of FFP to up to 5 days.46 Studies suggest that freshly thawed plasma may protect the endothelium in shock, a property that is lost upon postthaw storage.47 This movement exemplifies further the primacy of “inventory” versus “patient.” Provision of fresh blood for such patients would be a better therapeutic modality.

DEMISE OF A PARADIGM . . . The demise of fresh blood for transfusion occurred primarily as a result of the component or manufacturing paradigm, initially driven by the need for rapid and maximal plasma removal for FVIII. This paradigm was cemented further when the fear of infectious disease transmission resulted in the extensive range of prerelease tests mandated by regulators. These tests have certainly reduced the


risk of infectious disease transmission to insignificant levels in the developed economies, but an inventory of safe fresh blood from repeat, accredited donors is possible. If the authorities do not permit this, the automated batch-based testing of large numbers of donations can be modified to allow faster release of such an inventory. There is little common sense in exposing patients to multiple transfusions of inferior stored components when optimal therapy can be achieved with fewer transfusions of whole blood. The paradigm that is emerging from this tension would see the half of all transfusions prescribed for blood loss given as whole blood. This patient paradigm would certainly be viewed, in Kuhn’s terms, as incommensurable with the current product paradigm. The extraction of plasma from blood has continued, despite the great diminution of plasma FVIII, as blood services continue to earn revenue from selling recovered plasma to fractionators. As a by-product of RBC production, recovered plasma is considerably cheaper, in the free market, than is source plasma dedicated to fractionation. Many fractionators are therefore also unconscious supporters of the current paradigm. The driver for plasma procurement in Western countries is no longer FVIII, but the expensive logistically challenging quality criteria for plasma separation and storage are still geared to this protein. These criteria, which shape much of the practice of blood collection and processing, should be changed to reflect the requirements for immunoglobulin, a much more stable protein that used to be harvested from outdated blood before the product paradigm was imposed.48 This suggestion may be expected to be opposed by the large “quality control” industry that has arisen around the current paradigm. Rather than compromise the delivery of good quality blood transfusion, plasma for fractionation should be procured as what it is, a raw material for fractionation preferably produced through apheresis.

. . . AND EMERGENCE OF ANOTHER I have summed up the two pillars of the product paradigm as 1. 2.

Whole blood is to be avoided, as components are what the patient needs. Components allow us to serve more patients and maximize the “gift of life.”

I have suggested that the demise of whole blood was partially fuelled by a need for FVIII to treat hemophilia A. Faced with the modest results achieved in other parts of transfusion therapy 50 years ago, it is understandable that blood bankers threw their efforts into generating treatment, which had such dramatic effects. As long as there was no alternative, plasma-derived therapies for FVIII appeared a “sensible” use of blood. FVIII’s replacement by

IgG, concurrently with the development of recombinant products, ensured that a market for plasma “by-product” continues to exist to subsidize the cost of other components.49 This evolution has resulted in a disadvantageous position for other blood recipients requiring treatment for blood loss. The product paradigm has led to these patients receiving potentially inferior treatment. The second component—the inventory argument—is also untenable. If patients given RBCs must receive component supplementation, we are not achieving optimal blood use. Furthermore, the inherent concept of one donation, many patients has a link to safety. In the nowfamiliar pattern posed by emerging infectious agents, the first transfusion AIDS cases in Australia were three babies all transfused with the blood of one infected donor.50 Similar multiple transmissions have been reported for West Nile virus,51 babesiosis,52 and variant CreutzfeldtJakob disease.53 Given that increasing evidence indicates that RBCs54 and PLTs55 may be given safely below historically determined dosages, the pressures on component inventories should not impede better alignment to clinical needs. Lower dosages are also linked to a lower risk of the noninfectious adverse events of transfusion summarized in Thomson et al.20

THE PATIENT AS THE PARADIGM The new paradigm to succeed the product paradigm should be based on patient blood management as described by Thomson and colleagues.20 Blood management programs “falsify” (are demarcated from) the product paradigm by a potential to decrease blood usage while improving outcomes (Fig. 4). In contrast with the depressing projection of blood and donor increases under the current paradigm,56 increases that are steadily unachievable, a patient paradigm addresses the problem of supply more effectively, through blood management and correction of the component related problems outlined in this review. The new patient paradigm, demarcated, in Popperian terms, through rational blood usage from the product paradigm, addresses problems better (Fig. 5), an eminently Kuhnian and Popperian progression. The incommensurability of emerging paradigms to the established ones occupied Kuhn greatly, which may be expected to be equally vigorous in transfusion medicine. The evolving blood management programs pose a strong challenge to the blood bank establishment, wedded to a “more donors, more products” philosophy. Its embedment in the hospital or clinical environment is in contrast to the detached, centralized, and inventory-driven blood systems of the developed world. Funding bureaucracies may be expected to resist this paradigm shift, as the power to shape transfusion practice is regained by clinicians. Other opposing interests include commercial agencies Volume 51, January 2011

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vested in supplying the myriad of (expensive) consumables that are absorbed continuously by component manufacture. The position of the WHO appears to straddle the product and patient paradigm,57 suggesting a possible bridging role for this agency.

CONCLUSIONS While much of transfusion practice still operates within the tenets of the product paradigm—through normal practice in the Kuhnian sense—a growing literature supports the emergence of the new paradigm proposed in Fig. 5. The “incommensurability between the two paradigms is obvious. The demarcation between them is driven by the clinical needs of the patient. The next few years will see whether the revolution in transfusion medicine demanded through the new paradigm will occur, benefiting patients and donors, but discomforting many in the “blood industry.” These colleagues, who defend a paradigm that has delivered much good in its time, may well reflect on Popper’s words that “theory is the offspring of earlier dogmas, plus criticism,”14 drawing an obvious lineage for the new paradigm from the old. Kuhn would argue that the “incommensurability” between old and new paradigms leaves little room for compromise. perhaps, in our discipline of transfusion medicine, it may be possible to align more closely to Einstein’s words: “There could be no fairer destiny for any physical theory than that it should point the way to a more comprehensive theory, in which it lives on as a limiting case.”58 Progression to a better paradigm should address the problems of the present while retaining the good of the past. Fig. 4. Transfusion levels (A) and mortality (B) for transfused patients in Englewood Hospital and Medical Center (EHMC) compared to other demographics. Patient blood management, as described in Moskowitz et al.,59 is practiced at EHMC. CABG = coronary artery bypass graft.

Fig. 5. The proposed transfusion paradigm. 222 TRANSFUSION


CONFLICT OF INTEREST None.

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