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In the large , multicenter , randomized , controlled INFORM ( Informing Fresh versus Old Red Cell Management ) study , in-hospital mortality did not differ between patients who received transfusions of red blood cells ( RBCs ) stored for short periods of time and those who received RBCs stored longterm . 1 This is the latest study to assess outcomes related to the length of time for which blood is stored , and , according to lead author Nancy M . Heddle , MSc , its findings should end the debate about the impact of RBC storage length .

“ The results of the INFORM trial should reassure physicians that the routine use of fresher blood for hospitalized adults that require red [ blood ] cell transfusion is not justified ,” Prof . Heddle , an associate professor of pathology and molecular medicine at McMaster University in Ontario , Canada , told ASH Clinical News .

INFORM included adult patients who were hospitalized at six institutions in four countries ( Australia , Canada , Israel , and the United States ); patients were randomized 1:2 to receive transfusions of the freshest RBCs in the inventory ( short-term storage ; mean storage duration = 13 ± 7.6 days ) or the oldest available RBCs ( long-term storage ; mean storage duration = 23.6 ± 8.9 days ; p < 0.001 ). Patients were excluded if they :

• were expected to receive a massive transfusion ( a request for ≥10 red-cell units at a time )

• required blood that had not been cross-matched

• required autologous or directed transfusion

• had an indication for freshonly , red-cell transfusion

Some patients with alloimmunity to red-cell antigens were also excluded if it was difficult to find compatible blood . Patients undergoing cardiac surgery at one U . S . site and in the intensive care unit ( ICU ) at one

Canadian site were excluded due to competing studies .

Demographics , diagnoses , duration of hospital stay , and vital status at discharge were collected from hospital electronic medical records , and information on transfused red cells ( including blood type and storage duration ) were extracted from hospitals ’ electronic laboratory information systems . Patients were followed until in-hospital death or discharge .

In-hospital mortality ( the study ’ s primary endpoint ) was assessed only in patients with type A or O blood ( intention-to-treat cohort ), given the study ’ s requirement for a difference in the average storage duration to be at least 10 days , and this was difficult to achieve in patients with other less common blood types .

Between April 2012 and October 2015 , 24,736 patients met the

TABLE 1 . Transfusion Data 1

Variable

Median interval from randomization to issue of first red-cell unit for transfusion ( IQR ) inclusion criteria : 20,858 had type A or O blood and were randomized to receive short- ( n = 6,936 ) or long-term ( n = 13,922 ) stored RBCs . The median duration of hospital stay was 10 days for both the short- ( interquartile range [ IQR ] = 5-19 days ) and long-term storage groups ( IQR = 5-20 days ). See TABLE 1 for transfusion data .

There were 634 deaths ( 9.1 %) in the short-term storage group and 1,213 ( 8.7 %) in the long-term storage group , for an odds ratio of 1.05 ( 95 % CI 0.95-1.16 ; p = 0.34 ). At 30 days , the cumulative probability of death was 6.9 percent in the shortterm cohort versus 6.5 percent in the long-term cohort .

The authors added that , “ when the analysis was expanded to include the 24,736 patients with any blood type , the results were similar , with rates of death of 9.1 percent [ in the short-term group ] and 8.7

Short-Term Cohort ( n = 6,936 )

0.1 ( 0.0-0.5 ) percent [ in the long-term group ] ( OR = 1.04 ; 95 % CI 0.95-1.14 ; p = 0.38 ).”

When the authors conducted a subgroup analysis ( based on hospital site , country , blood type , and diagnosis ), no significant interactions were found . There also were no significant differences in mortality with short- or long-term storage of RBCs in high-risk subgroups :

• undergoing cardiovascular surgery ( 12.3 % vs . 11.2 %; p = 0.08 )

• in the ICU ( 13.3 % vs . 12.8 %; p = 0.52 )

• with cancer ( 8.4 % vs . 8.8 %; p = 0.82 )

The study is limited in its use of electronic databases that did not systematically record detailed

Long-Term Cohort ( n = 13,922 ) p Value

0.1 0.08

( 0.0-0.06 )

Median ( IQR ) 2 ( 2-4 )

Range 1-227 1-92 Number of red-cell transfusion episodes per patients * 0.78

Median ( IQR ) 1 ( 1-2 )

Range 1-87 1-58

Duration of storage of transfused red cells in days < 0.001 Mean 13 23.6

Median ( IQR ) 11 ( 8-16 )

2 ( 2-4 )

1 ( 1-2 )

23 ( 16-31 )

Duration of storage of transfused red cells per patient in days < 0.001

Median of the mean age of red cells transfused per patient ( IQR )

Median of the oldest red cells transfused per patient ( IQR )

Other transfusions

11 ( 8-15 )

12 ( 8-18 )

Platelets 1,289 ( 18.6 %)

Plasma 1,155 ( 16.7 %)

Cryoprecipitate 403 ( 5.8 %)

* Transfusion episode defined as all transfusions given on a single day . IQR = interquartile range

24 ( 18-30 )

27 ( 19-36 )

2,579 ( 18.5 %)

2,270 ( 16.3 %)

755 ( 5.4 %)

Continued on page 62

0.91

0.49

0.23

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