Risks of transfusion: outcome focus

Transfusion risks have been reported in texts with a focus on pathogen transmission. Today we have made strides in making our blood supply safer. Most blood bankers will herald their accomplishments by saying that the blood supply is the safest it has ever been and they are correct.1-4 Tremendous amounts of research dollars and technologic advances have occurred in making hepatitis C and human immunodeficiency virus (HIV) transmission extremely rare.2 This article will discuss those risks as well as a number of other routinely mentioned risks (i.e., ABO-Rh mismatch, transfusion related acute lung injury [TRALI], graft-versus-host disease [GVHD], etc.) In the past few years, however, new and groundbreaking research is being performed examining transfusion and outcome. Much of the focus of this article will be on that work and asking the all important question: Does transfusion do what it is intended to do—improve outcome or prevent adverse outcomes? Red cell (RBC) transfusions are administered to increase oxygen-carrying capacity. Unfortunately there is no single best clinical monitor that can tell us when to transfuse. There is disagreement as to when a transfusion is necessary or beneficial. This disagreement is because there is little research outlining when transfusions improve outcome. Transfusion is one of the most widely utilized medical interventions and has always been held in high esteem by practioners. It has not undergone prospective randomized testing to examine efficacy. We have a great deal of information about risks but very little data regarding efficacy. The trigger to transfuse has evolved over time. Evolved is the key word here because there have not been extensive (different disease entities and specific patient groups) bench or human studies delineating when it is either necessary or wise to transfuse. In the early 1900s, immediately after modern blood banking was born, the trigger to transfuse was a hemoglobin (Hb) level of approximately 3.5 to 4 g per dL.5 Interestingly, that number is the number at which human critical oxygen demand is found with anemia. The early transfusionists described that as the level they would encounter shock and congestive heart failure if patients did not receive a blood transfusion. In the 1920s the number rose to about 5 to 7 m per dL with the idea that transfusion should be a prophylactic treatment, not waiting until the adverse events of critical DO2 were encountered.5 That transfusion trigger remained until after the Second World War. In 1947, a single influential physician published his opinion that the best Hb level to transfuse at for surgery was 10 g per dL and that if a patient had lost approximately 15 percent of his or her circulating volume a unit (or two) of blood should be administered. This was not based on bench research or human outcomes research, but was one man's opinion. It was reprinted in every anesthesia and surgical text for the next 40 years. With the evolution of practice, it took on a near religious observance and can still be found in some institutions today. Only after the HIV crisis of the late 1980s have we realized that a more critical look at a transfusion trigger and outcome needs to be performed.1,6 To date only a very few small studies have been performed with proper prospective data gathering to help us understand the risk-to-benefit ratio of transfusion. For a number of years, from the 1970s through the 1980s, the risks of hepatitis B and C as transmitted by transfusion were widely recognized.5 It was estimated that that risk for patients to seroconvert from transfusion was approximately 10 percent. It was widely accepted that transfusion was “good,” and there was no research conducted comparing risks and benefits of transfusion. The following statistics for resulting adverse outcomes are merely speculative but are staggering.6 If one assumes that between the early 1970s and the late 1980s some 30 to 50 million people were transfused with a viral seroconversion rate of 10 percent that means that some 3 to 5 million cases of new hepatitis were transmitted. Of these approximately 50 percent proceeded to chronic active hepatitis (1.5-2.5 million) and of those approximately 20 percent (300,000-500,000) proceeded to cirrhosis. That means that over that 20-year period by iatrogenic means alone we have created a major epidemic of cirrhosis and hepatomas, some of which we are still caring for today. In my career as a hepatic transplant anesthesiologist I have cared for at least 50 patients with cirrhosis undergoing liver transplantation secondary to transfusion hepatitis. Were those transfusions life-saving or necessary? When the HIV crisis became a major epidemic in the developed world, transfusion medicine came under very direct scrutiny. Questions were raised as to the vigilance of blood bankers and how information had been disseminated with regards to the risks of transfusion. The 1990s saw tremendous strides in reduction of the pathogen transmission risks of transfusion and outcome. Variant Creutzfeldt-Jacob disease (vCJD) or mad cow disease has captured the political events of Europe, and recently a single cow infected that crossed the border between Canada and the United States caused widespread financial events. For many years the blood banking industry prided itself on the fact that no single case of vCJD had been transmitted by transfusion. Just within the past 6 months the UK has announced the first case of transfusion-transmitted vCJD. Others certainly a wait us in the future. Advances in surrogate testing, enzymes, and voluntary disqualifications and the eventual establishment of nucleic acid testing (NAT; 1996-1997) radically reduced the risk of hepatitis C and HIV via transfusion. Today the risks of these infectious complications being transmitted through transfusion are vanishingly small (Table 1).2 Hepatitis B remains a significant risk but other adverse outcomes are more prevalent. NAT, an outgrowth of the genetic revolution, has made our blood supply safer not just from HIV and hepatitis C. In the past 3 years the specter of West Nile virus has arisen. Within 2 years of appreciation of it as a transfusion pathogen risk, a new NAT was devised and that has been applied to all blood harvested, the end result being that the risk of West Nile virus transmission has fallen from 1 in 400 to 4000 units transfused in 2001 (summer) to about 1 in 2.4 million units today.7 New viruses will be constantly cropping up in our blood supply, and we cannot test for them all. Transfusion-transmitted virus (TTV) is present in 52 percent (8-82 percent reported) of all units infused and it is simply not tested or detected at this time.8 Cytomegalovirus and Epstein-Barr virus are present in a large number of units. If a patient is negative for these viruses, he or she may well receive the virus through transfusion. If a patient is immunosuppressed and negative for these viruses, however, blood tested for these viruses is available. There is the threat of severe acute respiratory syndrome and avian flu virus looming on the horizon as well as any number of other unknown viruses that could be finding their way into our blood supply. Universal pathogen destruction is under testing for FDA approval at this time. If it is successfully brought forward, however, this pathogen reduction technology will be costly and not available for every unit of blood transfused. A wide number of bothersome and less widely publicized adverse events with blood transfusion are often discussed in the literature (Table 2).2 These are thought to be less important often in such discussions simply because they do not gather the big headlines of HIV and hepatitis. If you were a patient and they happened to you, however, they would be an adverse outcome. Febrile reactions are very common and cause transfusions to be halted, work-ups to be begun, and perhaps even longer stays in the hospital. Allergic reactions can be minor or all the way to catastrophic with anaphylactic events. Minor ABO-Rh mismatch is far too common and delayed RBC destruction is also far too common. Thankfully, major ABO-Rh RBC lysis with disseminated coagulation and death occurs only in about 1 in 100,000 units transfused. That is still more common than hepatitis B today and is fully preventable. Bacterial contamination of banked units is a rare but catastrophic event. RBC bacterial contamination and is discussed by the FDA and the through and The RBC held for up to are at and are less to than at or and are found in a transfusion either or units are for up to 5 in the blood at Bacterial contamination has been estimated to in a significant number of these perhaps as often as 1 in 400 to 1 in units. The risk to patients is to because voluntary to the FDA is It is however, that the risk of a transfusion could be as high as 1 in to units. In the past months the has that all and blood to their for bacterial With that being a significant of units are being cannot to the that every unit is but some be Most do not this as a risk of transfusion and would look for other of if with transfusion. There are to increase the for from 5 to 7 but no has been made in that events with transfusion can one of the more discussed outcomes These are the viral risks and some of the risks of transfusion. if it to you, even if it is only a bothersome risk, it still has adverse When and about adverse outcomes in their of they to the and bacterial congestive heart failure and Transfusion of blood has been to prevent some of these adverse events. when one the of RBC in to the for adverse outcomes and with to and the of and RBC are administered with the idea of either an oxygen or oxygen-carrying capacity. and are administered either to active or to prevent in patients with or It has always been that these work and patients RBC transfusions today are on the of at in the blood blood is available but it should be that it can be in some if are and they a number of The are to such the blood and by of it can have a very of the and it can in the to of per or The is well but the within of The in available the Hb in to and when up oxygen with tremendous however, do not the oxygen to It has been estimated that oxygen from circulating other and even from A prospective of oxygen to in patients after surgery found that the transfusion of 1 or 2 units of did to improve oxygen to The to percent however, radically oxygen the idea that one is to increase oxygen-carrying may not be That oxygen-carrying however, may be or the of oxygen to the that it is to utilized in the has an of to at transfusion. In the unit transfused is by about 5 is if is than 5 transfused the of to be as the The is and the is the to can between 5 and to Of is the fact that at only about percent of are even of for transfused. 30 percent are or merely that are still are and to in the that are approximately 20 to 30 percent of their cell and their are through to that increase in number and in number of per over the of These with oxygen and to some and events with transfusion of In just to be it has been that patients transfused either heart surgery or in the critical units have after transfusion of RBC The as by has that patients transfused with have oxygen supply than transfusion. In of the it has been that if shock is the blood is When the circulating volume is with the blood to When banked blood is however, only about 10 to 15 percent of blood is and it is how after volume remains In studies of the and oxygen to the in it is also that these are either not to oxygen supply demand or made In studies of oxygen critical DO2 were at a Hb level if transfused blood was That means that as by critical oxygen is more or at a Hb level in the of transfused as to anemia. work from has been Most of the work the of and Hb on outcome. of these from the surgical that is with adverse and patients and after surgery and that no increase in was until the about 15 percent It was only at that level that and the after heart surgery and did that there was a between after surgery and an increase in and in more than on These found a increase in to and other adverse outcomes with on all of these studies have in common is that they also did not look at transfusion. In the was that be and should be with transfusion. It is most however, that transfusion was a surrogate of and transfusion one cannot be it is oxygen-carrying to or of transfusion itself that the adverse A large of for surgery was at the In that cases of were found in cases of surgery between and was found to have an with and the article was to that When the article is however, one that the is between the of disease and an within of heart surgery the with was with as The of a transfusion such as of and transfusion (RBC) itself was with When was comparing Hb and other were as or more important than Hb This the with of the research that today. There to be a Hb and adverse events. If one the data that in from it is that they can It is only at a Hb level of approximately 3 to 5 g per dL that data This level of Hb to what is as the critical Hb level from studies of critical DO2 is the at which from to and the longer an critical DO2 the more is to In work from as well as other the Hb level to critical DO2 is approximately 3 to 3.5 g to It is not that in clinical that the level of critical work has that when blood is transfused the way as human banked that the Hb of critical DO2 is that shock is more with the of transfused of the on more than patients undergoing surgery adverse events and for transfusion was in this data were available on the on but the unit did have a to outcome. the of the patients volume in the transfusion trigger of the transfusion The was related to and those patients with the had the and high risk the death Transfusion was related to medical (i.e., transfusion not to patient That means that we as do not transfuse based on patient needs but on of transfusion trigger that are These data did with when risk and were into with an to adverse in that had the adverse research from the literature data from the patients transfused the most have In the surgery literature those patients with the most transfusions to have the risk for are the in the patients transfused the most as are These data are also when of risk are It however, that those patients with the most and most well be the most Just as in the however, transfusion as an of adverse outcome the of of injury It as transfusion trigger was of of injury and some of the adverse the was from the This patients the of Of all those a transfusion for should be to from oxygen-carrying with transfusion. The had patients but after of of patients the data reported about of the It was to examine only patients over should did transfusion in all the but with not have an on In that it was found that were by transfusion if patients had a on to the and also had an The that this outcome only about approximately percent of the There was no to for a of data no with or in the and it was that did not the When the and those not are however, they are far from patients were in the were from those in the The had many more more than the number of patients were as do not and had less than the interventions and surgical Most the of blood by transfusion was very in this and it simply to that any today would not transfusion in a patient with an there were other such as a do not that be with a of transfusion When the outcome was it is very to understand how with do not and can be as near the of this widely article was that in patients with a 10 g per dL or 30 to percent transfusion trigger is The data is far from and a The for those patients transfused and for those not transfused. patients not transfused had approximately than those that one or more units of their These data were after events and with from from surgery for those transfused and not In a of transfusion it was found that transfusion had important on outcome. occurred at the rate in patients transfused to those not transfused. This finding was not only for the near but for up to the months of These did statistics and significant by statistics patient is a based on the number and of his or her from one are based on to other patients with and the is thought to be the best way to from large The over up and was still after with those patients transfused a death rate of those not transfused. These are but do the of and the of early from interventions have that early with and can the of early and as well as longer The that transfusion has been with to surgery and also to on A large number of studies from have an between transfusion and or has been with transfusion the that period the for transplantation was to that patients the of transplantation units of transfusion. This was that the would have less It was that a unit of blood would the rate and of In surgery a number of have a between the number of units transfused and the risk of In one article it was estimated that the risk of 5 percent per unit on blood or That of however, could not be as the or the most important for of in the hospital. In a large the number of patients It was that most patients a but anemia. With the of only 1 unit of blood however, there was a increase in and That ratio was by as as when transfusions were but more adverse events were when transfusion outcome was related to death In the infectious complications have been and between and In a number of prospective randomized it has been that the risk of infectious complications from to if blood is utilized for transfusion to it is that blood can still have and not all is by the of The literature on and is less with and has some of transfusion at the of and the is that of blood transfusion may increase the rate of events or either have not been as widely or have not to have as a The to be caused by a number of The blood which when transfused can and has been in the for up to 1 after transfusion and the for some period of to the A wide of are in and These the from and even these would to a This is a very literature with a large number of have that the to blood will or the of by transfusion. That to be at this studies have with and large however, have little or no a of of in the by if blood was for transfusion. The this to be It however, be of little or no clinical Of one should look at the between those transfused and those not transfused. If these patients were not their of was approximately the of for those transfused and the of or blood is in to transfusion. from other the those transfused longer and had more complications to those not In some of these studies had no on or infectious the of all transfusion was are in when data from the one it is important to that and Hb not that transfusion will improve outcome. It is important to understand that even has been performed and that there is a significant between transfusion and adverse cannot be Only prospective randomized can to the between the risks of and outcome with the risks of transfusion The are to be for asking on have to adverse outcome and transfusion those risks of adverse outcome. failure after heart surgery is thought to be to and of the oxygen-carrying of blood may have a with When this was it was found that there is a and direct between the in and the and most the of transfusion not this if should have the of the and that did not With level of transfusion the were but the of than That is to all the regarding transfusion and of oxygen-carrying capacity. the of or the of blood on and oxygen all could a in this is not just a risk of on but most is made by the of transfusion. more blood not it but to the failure even with from randomized of transfusion are and not widely transfusion has not been tested as a would be for FDA Transfusion has of an evolution of in Only today a few prospective randomized studies of transfusion and transfusion for heart surgery with of transfusion These no in outcome in more than patients and his was that was well and in the prospective of transfusion to date found significant in those transfused at This was a by units with patients randomized to receive transfusion at either 10 or 7 g per transfusion the and the new of these patients had respiratory and other critical The data a in the that had a more transfusion trigger but it was significant only at the level of In those patients and those with however, there was a significant in in those patients transfused was less in those not transfused as in the data was outcome in those patients transfused more The number of and rate of and respiratory syndrome was less in those patients transfused with less blood or at a A of patients with severe disease was in a In those blood transfusion did not improve outcome or prevent was not but those patients transfused less had a rate of This was a finding to that from the surgery patients more blood had more The between these and studies is that studies were prospective and and the data are has for the of blood for in our most of This the as in this article and that patients may well be either not from transfusion or being by the of banked that we to demand blood but that there is little in the way of an industry or to widespread demand for such a of the prospective of transfusion there are only a very and found that there is a but significant to not and is as of all the available prospective randomized studies of transfusion. that transfusion than more of with from and The just discussed regarding RBC transfusions are with to are utilized either to prevent or to from or Today the demand for is in with transplantation and It is a in these that those patients the most number and most transfusions have the randomized can be performed here to an of transfusion. the patients with the most or of are the most to receive are either from single as a of RBC or through The units are for up to 5 in the blood at on The the are and with as well as and of many can as high as to the in the itself is and very from the of when it was undergoing testing FDA were for and adverse outcomes were from patients were a of transfusion as well as outcomes in patients the early to These patients were and patients surgery were and other were transfusion was with adverse The of and death were all with transfusion. was by about in patients with transfusions and death by up to These up to and with the significant after for In a new of patients from all over the world, it was found that early of after heart surgery In the of this it was also that the of transfusion in the on there was an found between the of transfusions (i.e., and adverse has been in this the by research cannot cause and The are however, and the up in many the case for of Today we have no for however, at least in heart wide in is the the new research are and should at the least demand data alone cannot will from a transfusion and that could increase the risk for adverse events outcomes in surgery outcome with in and with from no In the data on outcomes and transfusion are There are few if any that transfusion patient outcome. The only article from a large outcome is and should not be The of between transfusion and with and The only prospective randomized of transfusion either no in outcomes with transfusion or outcomes in those patients with less blood or transfusion is well until near critical DO2 is The of transfusions are is are more randomized in large of patients with disease Transfusion is in our medical that to date such research has been if not The of still to be at some in the future. Only we have will of outcome be more or for many

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