Effect of Short-Term vs. Long-Term Blood Storage on Mortality after

Transfusion

DR VASIF MAYAN MC,M2 unit, Gmkmch

INFORM TRIAL

Heddle et al.NEJM October 2016

•Red-cell transfusion is one of the most common medical interventions.

•Blood is stored for up to 42 days before transfusion.

•Approximately 15 million red blood cell (RBC) units are transfused annually in the United States•About 85 million are transfused annually worldwide

INTRODUCTION

AABB Guidelines for red cell transfusion

• Preserved blood cells undergo progressive functional and structural changes that reduce oxygen delivery to tissues• The release of extracellular vesicles and cell-free DNA during

storage may cause a hypercoagulable state

• STORAGE LESION : amalgamation of reversible and irreversible changes that begin after 2 to 3 weeks of storage, progress with duration of storage and reduce red-cell function and viability after transfusion

• small membrane vesicles that are released from cells upon activation or during apoptosis.• Cause coagulation by exposure of negatively charged phospholipids and

tissue factor• are present in the circulation of healthy subjects• Microparticles are present in atherosclerotic plaques• elevated numbers of microparticles are seen in • DIC• ACS• POVD• DM

• Red blood cells’ ageing in blood bank conditions clearly differs from physiological in vivo ageing• conditions to which red blood cells are exposed during storage such as

temperature and nature of the medium are dramatically different from in vivo conditions• RBCs change shape; their membranes become more rigid and there

is a disruption of phospholipids asymmetry and release of fragments and MPs.

• There is decreased deformability which can impede microvascular flow.• depletion of 2,3-diphosphoglycerate (2,3-DPG) shifts the oxyhemoglobin

dissociation curve to the left and reduces oxygen delivery.

Studies on Microparticles

• Precise consequences of storage, including storage lesions and MPs release, on transfusion efficiency are not clearly understood.

• Polytransfused recipients are often in poor condition, Hence it is difficult to attribute clearly an event to transfusion rather than on the clinical situation of the recipient.

• Randomized controlled trials have not shown harm in transfusing red-cell units with a longer duration versus a shorter duration of storage

What do Studies say?

• Packed Cells stored for more than 28 days was associated with an increased incidence of deep vein thrombosis and death from multi-organ failure

• In patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than 2 weeks was associated with a significantly increased risk of postoperative complications as well as reduced short-term and long-term survival.

•  Informing Fresh versus Old Red Cell Management (INFORM)• Randomized Multicentric trial (APRIL 2012 to OCTOBER 2015)• 6 Hospital• 4 countries (Canada, Australia, Israel, USA)• Patients enrolled in a 1:2 ratio to avoid excessive outdating of cells

STUDY DESIGN

n=20,858Short term storage

n=6,936

Long term storagen= 13,922

• > 18 years of age needing packed red cell transfusion for primary analysis• Only A and O group were selected

•EXCLUSION CRITERIA• Patients needing massive transfusion > 10 or more red-cell units at a time• Requiring autologous or directed transfusion• Patients with alloimmunity to red-cell antigens• Patients who were undergoing cardiac surgery

INCLUSION CRITERIA

SHORT TERM STORAGE

LONG TERM STORAGE

No. of red-cell units transfused per patient

2 PC 2 PC

Duration of storage of transfused red cells

13.0±7.6 23.6± 8.9

p value<0.001Median Duration of storage of

transfused red cells11 23

RESULTS76,356 transfusions

Short term storage 25,466

Long term storage50,890

SHORT TERM STORAGE

LONG TERM STORAGE

Mortality 634 ( 9.1%) 1213 (8.7%)Median duration of hospital stay 10 days 10 daysCumulative probability of death

at 30 days6.9% 6.5%

MORTALITY in subgroups SHORT TERM STORAGE

LONG TERM STORAGE

Cardiovascular surgeries 12.3% 11.2%ICU 13.3% 12.8%

Cancer 8.4% 8.8%

•No significant difference in the rate of death among patients who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood.

•No association between the age of blood analyzed as a continuous variable and in-hospital mortality

•No benefit of fresher blood was seen in the primary and secondary analyses

CONCLUSION

• ADDITION of• Erythropoietic Agents• Hemostatic agents

NO need to WORRY !