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karl landsteiner discovered the abo blood group system , which allowed blood products to be administered without precipitating immediate severe transfusion reactions .
the logistics for collecting and storing blood followed at the time of the onset of world war i , with the introduction of the anticoagulant trisodium citrate to prevent clotting .
the mid-20th century was focused on attempts to have adequate blood supply on hand , as operative procedures became technically more complex and medical specialties known to consume large quantities of blood and blood products , such as transplantation , began to emerge .
contamination of the blood supply also was becoming a concern , and in the early 1970s it was recognized that the incidence of hepatitis transmission could be decreased by excluding paid donors . screening for hepatitis b
until 1980 , blood donations were only screened for syphilis serology and hepatitis b. since then , nine new blood tests have been introduced in an attempt to reduce the transmission of hiv-1 , hiv-2 , hepatitis c , and human t - cell leukemia virus ( htlv)-i and htlv - ii . by 1996 ,
anti - hiv-1 and p24 antigen testing were routinely performed , decreasing the transmission of hiv . despite these advances , there continues to be major concerns with our blood supply because of bovine spongiform encephalopathy , prion transmission , and unknown pathogens .
as we continue into the new millennium , interests are shifting toward technologic advances in pathogen inactivation and modification of the red blood cell ( rbc ) surface to reduce antigenicity .
leukoreduction is a process in which the white cells , ordinarily present in collected blood components , are intentionally reduced in number . through the use of centrifugation or filtration
cytomegalovirus ( cmv ) , htlv - i , and htlv - ii are only transmitted by transfusion of cellular products , and if universal leukoreduction were to be adopted then these viruses would be removed by filtration , and it would no longer be necessary to test for these potential contaminants . thus , an advantage of leukoreduction is its effectiveness in reducing the transmission of cell - associated viruses , especially cmv , herpesviruses , and epstein  barr virus .
leukoreduction filters also bind the trypanosoma cruzi parasite and may decrease the incidence of transfusion - associated chagas ' disease . in 1998 ,
the blood products advisory committee of the us food and drug administration unanimously voted in favor of universal leukoreduction of blood components , but its members agreed that sufficient evidence - based data were lacking .
thus , both leukoreduced and nonleukoreduced blood components currently remain approved by the food and drug administration . in 1994 and 1997 ,
the percentage of blood components transfused in the usa that were leukoreduced were 17.6% and 18.3% and for platelets 16.5% and 15.5% , respectively .
surgical patients and those with gastrointestinal bleeds are the groups most likely to receive nonleukoreduced blood , in part because of the emergent need for blood . when a unit of blood ( approximately 500 ml ) is collected , about 2 billion ( 2  10 ) white cells are present . even with blood component processing , 90% of these cells remain with the rbcs , primarily as granulocytes ; 8% of cells ( 2 million ) remain with platelets as mononuclear cells ; and 2% of cells ( 10 million ) remain in an aliquot of fresh frozen plasma .
the intent of leukoreduction is to decrease the number of white cells in the aliquot , but even the 0.0005% of cells left after leukoreduction leaves 5000 residual leukocytes .
filtering of the white cells can lead to a 510% loss in the number of rbcs recovered per unit .
these losses may be justified , however , because they are balanced in part by the improved quality of the filtered rbc unit .
although it is the most common transfusion reaction , febrile - associated transfusion reaction is due to clerical error and is self - limited .
universal prestorage leukoreduction has resulted in decreased fever episodes and antibiotic use after rbc transfusion , with a reduction in mortality .
suggestions have also been made that transfusion - related acute lung injury may be due to the presence of allogeneic leukocytes in stored rbc products , although most cases of transfusion - related acute lung injury are believed to be due to the passive transfusion of anti - hla antibodies that react with recipient neutrophils .
up to 30% of platelet transfusions lead to a febrile reaction ; however , this may be secondary to the release of platelet - specific chemokines rather than the chemokines released by contaminating leukocytes . in a multicenter study conducted in patients with leukemia and sponsored by the us national institutes of health , a difference in platelet refractoriness did not lead to clinical differences . on the other hand , the american society of clinical oncology found level i grade a evidence , and recommended that only leukoreduced products be used in patients with acute myeloid leukemia .
this is because alloimmunization against histocompatibility antigens occurs in many recipients of multiple random donor platelet transfusions , and is the most important long - term complication of platelet transfusion .
the most common form used in europe and the usa is prestorage leukoreduction , which removes leukocytes before they can contribute to the storage lesion ( rbcs ) or transfusion reactions ( platelets / rbcs ) .
the process allows the opportunity for better quality control , has not been associated with acute hypotensive episodes , and eliminates the need for transfusion services to manage filter inventories and for nursing staff to maintain multiple blood administration protocols .
prestorage leukoreduction not only decreases the incidence of certain virus transmissions but also eliminates the delay associated with filtering blood in a patient who requires blood to be administered urgently .
only one type of filter is needed , allowing standardization to occur , obviating the need to train technicians and nurses on the procedure , and eliminating the clotting of filters during a transfusion .
barr virus ; hhv , human herpesvirus ; htlv , human t - cell leukemia virus ; rbc , red blood cell .
one advantage that poststorage filtration may have is that the filter used with transfusion administration may remove undesired substances that accumulate during storage .
disadvantages of leukoreduction a study of elective orthopedic surgery patients confirmed the presence of t - cell - mediated immunity after allogeneic transfusion . with buffy coat
depleted or white blood cell filtered rbcs , alloantigen - induced t - cell proliferation was significantly reduced . however , in a group of patients with advanced hiv infection , in which t - cell immunity is important , leukoreduction provided no clinical benefit with respect to hiv , cmv , or cytokine activation .
six studies [ 8 - 13 ] suggested that leukoreduction is beneficial in preventing postoperative complications in patients undergoing surgery , but two studies   showed no benefit . because of issues regarding study design , data analysis , and other factors , these findings are still a subject of debate .
on the other hand , two studies   were published that reported evidence of improvement in morbidity and mortality .
one large study   found a 50% decrease in the mortality rate and a decrease in postoperative infection as a secondary end - point in patients undergoing cardiac surgery receiving leukoreduced blood .
the largest prospective randomized study of leukoreduction   enrolled 2780 patients , and documented no differences in the outcome measures studied , including in - hospital mortality , hospital length of stay , intensive care unit length of stay , postoperative length of stay , antibiotic usage , and readmission rate .
subgroup analyses based on age , sex , amount of blood transfused , and category of surgical procedure showed no effect of leukocyte reduction .
patients who received leukocyte - reduced blood exhibited a lower incidence of febrile reactions ( p = 0.06 ) . in that important
study no beneficial effect from leukocyte reduction was demonstrated . a recent meta - analysis   reviewed
there was no association between transfusion and mortality across 14 trials reporting on short - term mortality ( summary odds ratio 1.20 , 95% confidence interval 0.871.65 ) or across three trials reporting on long - term mortality ( summary odds ratio 0.87 , 95% confidence interval 0.641.19 ) .
subgroup analysis suggested an association between non - leukocyte - reduced blood transfusion and increased short - term mortality in cardiac surgery patients .
no prospective randomized studies have yet investigated whether leukoreduction of blood is associated with improved outcome in critically ill patients specifically .
leukoreduction of blood can add approximately $ 100 to the cost of a unit of blood . in the state of rhode island , with a population of 1 million , the cost of leukoreduction is us$1,466,250 . extrapolating this figure to universal leukoreduction in the entire usa yields an annual cost of around $ 319 million , but
this does not take into account the above - mentioned cost savings associated with reduced time , resources , and effort ( table 2 ) .
emerging scientific and clinical evidence demonstrates that leukoreduction technology is an effective means to reduce the risk for three complications of transfusions : hla alloimmunization , cmv transmission , and recurrent febrile nonhemolytic transfusion reactions . notwithstanding the ongoing debate on the merits versus the disadvantages of universal leukoreduction , most projections indicate that within the next few years all blood in the usa will be leukoreduced .
cmv = cytomegalovirus ; htlv = human t - cell leukemia virus ; rbc = red blood cell .
the safety of the blood supply has been a concern over the past 2030 years because of the transmission of infectious diseases . 
 blood is still routinely tested for viruses , and leukoreduction is an effective strategy to reduce the transmission of cell - associated viruses . 
 clinically , the benefits of leukoreduction include decreases in transfusion reactions , hla alloimmunization , infections , fever episodes , and antibiotic use . 
 although leukoreduction will add cost to a unit of blood , projections indicate that leukoreduced blood will become the standard of care .