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

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

2. INFORM TRIAL
Heddle et al.
NEJM October 2016

3. •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

4. AABB Guidelines for red cell transfusion

6. • 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

7. • 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

10. • 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.

14. Studies on Microparticles

15. • 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

17. What do Studies say?

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

21. • 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.

28. • 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=20,858
Short term storage
n=6,936
Long term storage
n= 13,922

29. • > 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

32. 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<0.001
Median Duration of storage of transfused
red cells
11 23
RESULTS
76,356
Short term storage
25,466
Long term storage
50,890

33. SHORT TERM
STORAGE
LONG TERM
STORAGE
Mortality 634 ( 9.1%) 1213 (8.7%)
Median duration of hospital stay 10 days 10 days
Cumulative probability of death at 30
days
6.9% 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%

36. • 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

37. • ADDITION of
• Erythropoietic Agents
• Hemostatic agents

38. NO need to WORRY !