Transcript Storage Time and After Transfusion Survival

Storage Time and
After Transfusion
Survival
Omar Alsuhaibani
Transfusion Medicine Fellow
Journal Club
May 18th, 2010
Objectives
 Storage
lesion & relative background
information
 Previous study quick review
 Ongoing study (ABLE)
 Article review
 Critical appraisal
 Discussion & questions
Background
Storage lesion is an amalgamation
of reversible and irreversible
changes that begin after 2 to 3
weeks of storage
Background
 Storage
lesion
- loss of deformability
- morphologic changes
- depletion of ATP & 2,3-DPG
 These changes decrease O2 transporting
capacity & impair capillary passage
“storage lesion”
“storage lesion”
42-Day Post-storage pRBC Characteristics after
Resususpension in AS
Vox Sang 1998;75:212-217
Characteristic
Pre-storage
Post-storage
pH
6.8
6.4
ATP (μmol/g Hb)
4.1
2.9
DPG (μmol /g Hb)
9.0
0.3
Potassium (mEq/L) 2.4
63
Glucose (mg/dl)
402
608
Plasma Hb (mg/dl) 39
372
Hemolysis (%)
0.61
--
The effect of red-cell age on
outcomes
 Inverse
association between changes in
gastric intramucosal pH and the age of
transfused blood for patients who received
red cells stored for more than 15 days
 evidence of splanchnic ischemia
developed in patients given older blood
Marik PE,. Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993
Background



Previous studies have found suggestive evidence of
various adverse consequences;
- increased mortality
- increased LOS
- infectious complications
- thrombosis
- multiorgan failure
However, studies were criticized being small and failed
to control important sources of error
No large RCT of fresh vs stored RBCs has been
completed
Koch and colleagues - 2008

patients given red-cell transfusions during
coronary-artery bypass grafting, heart-valve
surgery, or both
 between June 30, 1998, and January 30, 2006.
 2872 patients received 8802 units of blood that
had been stored for 14 days or less (“newer
blood”),
 3130 patients received 10,782 units of blood that
had been stored for more than 14 days (“older
blood”).
Koch and colleagues - 2008

median duration of storage was 11 days for newer blood
and 20 days for older blood.
 patients who were given older units had higher rates of
in-hospital mortality (2.8% vs. 1.7%, P = 0.004),
intubation beyond 72 hours (9.7% vs. 5.6%, P<0.001),
renal failure (2.7% vs. 1.6%, P = 0.003), and sepsis or
septicemia (4.0% vs. 2.8%, P = 0.01).
 complications were more common in patients given older
blood (25.9% vs. 22.4%, P = 0.001).
 older blood was associated with an increase in the riskadjusted rate of the composite outcome (P = 0.03).
 at 1 year, mortality was significantly less in patients given
newer blood (7.4% vs. 11.0%, P<0.001).
Koch and colleagues - 2008
“ 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.’
Ongoing study

Age of BLood Evaluation (ABLE) trial in the
resuscitation of critically ill patients
 Double blind randomised parallel trial
 The transfusion of fresh leuko-reduced red cells
(stored for less than 8 days) will lead to a 5% or
greater improvement in 90 day all cause
mortality and clinically important decreases in
morbidity in a vulnerable population of critically
ill patients.
ABLE - Inclusion criteria
Patients who:
1. Have had a request for a first red cell unit
transfusion in the Intensive Care Unit (ICU), and
2. Have an anticipated length of invasive and/or
non-invasive continuous positive airway
pressure (CPAP) or bi-level positive airway
pressure (BIPAP) mechanical ventilation of at
least 48 hours once enrolled, as estimated by
the attending physician
ABLE – exclusion criteria
- less than 16 years of age
- previously enrolled in the ABLE study
- already been transfused with red cells during the current
hospitalisation
- obvious terminal illness documented in the medical record with a
life expectancy of less than 3 months
- undergone routine cardiac surgical care
- a decision to withdraw/withhold some critical care had been made
- obviously brain dead
- no red cells with a storage time of 7 days or less available in the
blood bank that cannot be transported from the blood supplier
- require more than 1 unit of uncross-matched red cells
- a known objection to blood transfusions
- autologous blood donations
- difficulties in securing blood products (rare blood groups), and who
are difficult to match
ABLE


Primary outcome:
90-day all cause mortality.
Secondary outcomes:
1. Other mortality rates and survival times as measured at ICU
discharge, hospital discharge, 28 days and 6 months post-discharge
2. Number of cases of multiple organ dysfunction syndrome
(MODS), highest number of organ failures per patient, MODS score
and time to development of MODS as measured while in the ICU
3. Serious nosocomial infections including:
3.1. Nosocomial pneumonia
3.2. Deep tissue infections (e.g. peritonitis, mediastinitis)
3.3. Bacteraemia from organisms not considered normal skin
flora and judged important enough to treat by the attending team, as
measured while in the ICU
4. Adverse events and transfusion reactions as measured while in
ICU
5. Length of stay (ICU and hospital)
6. Length of time requiring respiratory, haemodynamic and renal
support as measured while in ICU
Is
like
?!
Study design & methods
a
large, retrospective cohort study using a
population-based database of blood
transfusion recipients
 all recipients of at least one RBC
transfusion in Sweden and Denmark
between 1995 and 2002, as recorded in
the Scandinavian Donations and
Transfusions (SCANDAT) database.
Study design & methods

Component production and transfusion practice
follow very similar national guidelines
 Maximum storage time for RBCs in SAGM
solution has been 42 days in Sweden and 35
days in Denmark
 Units that were leuko-reduced through filtering
or other means were used to a varying but
generally increasing extent throughout the entire
study period
Study design & methods

Swedish and Danish databases were merged to
form the Scandinavian Donations and
Transfusions (SCANDAT) database
 The investigation was limited to patients aged 15
to 90 years with known blood type, who had not
received any transfusions in the 2 years
preceding the index transfusion
 Transfusions were grouped into episodes
containing an exposure period and a follow-up
period, both of which were varied to assess
short- and long-term survival in relation to RBC
storage time.
Study design & methods
Exclusions :
 autologous units
 ABO-nonidentical units
 units from unknown donors
 units of unknown storage time that were
transfused during the exposure period
Study design & methods

Short-term survival was assessed using a 1-day
exposure period and an overlapping 7-day
follow-up period (i.e., from Day 1 through Day 7)
 Long-term survival was assessed using a 7-day
exposure period with follow-up from Day 8
through Day 730 (i.e., 2 years).
 Follow-up was terminated upon death,
emigration, or end of registration in the
SCANDAT database (December 31,2002)
Study design & methods
 exposure
categories were 0-9, 10-19, 2029, or 30-42 days old
 mixed category, with recipients of multiple
units that fell into more than one age class
 freshly prepared units used for special
indications e.g. when units are prepared
for patients with irregular RBC antibodies,
recipients of 10- to 19-day-old units were
used as the reference group
Statistical Analysis


The relative risks of death, expressed as hazard ratios,
were estimated using Cox proportional hazards
regression
Six indication groups were established according to a
sequential algorithm:
1) trauma
2) nontrauma, cardiovascular surgery;
3) nontrauma, noncardiovascular surgery for malignant
Disease
4) nontrauma, noncardiovascular, nonmalignancy, major
surgery
5) other care for hematologic malignancy
6) other hospital care.
Statistical Analysis
 All
variables were treated as categorical
except age, calendar period, and number
of RBC transfusions
 Possible statistical interactions between
the main exposure and country, sex, age,
calendar time, and number of transfusions
were explored with likelihood ratio tests
 All p values were two-sided.
Statistical Analysis
 The
proportional hazards assumption was
evaluated using Schoenfeld residuals from
the main models
 All statistical analyses were conducted
using computer software
 Since some patients experienced more
than one transfusion episode, robust
variance estimates were used
Results

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

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After various exclusions, 404,959 transfusion episodes
remained for analysis.
The 7-day risk of death was similar in all exposure
groups,
a tendency for a higher risk emerged among recipients
of blood stored for 30 to 42 days (hazard ratio, 1.05;
95% confidence interval [CI], 0.97-1.12), compared to
recipients of blood stored for 10 to 19 days.
With 2-year follow-up, this excess remained at the same
level (hazard ratio, 1.05; 95% CI, 1.02-1.08).
No dose response pattern was revealed and no
differential effect was seen when the analyses were
restricted to recipients of leuko-reduced units only.
Conclusions

This large study showed a 5% excess mortality
confined exclusively to recipients of RBCs stored
for 30 days or more.
 The observed excess in this group, which
remained constant across follow-up but attained
significance only in the long-term follow-up,
seemed more compatible with a higher baseline
risk among the recipients of the very oldest units
than with an actual deleterious effect of the old
units per se.
Conclusions

Confounding may have inflated any true effect of
older RBCs, and the true effect, if any, in the
combined Swedish and Danish transfusion
recipient population is likely to be less than what
was observed in this investigation
 The excess seems more compatible with
recently published review articles that have
concluded that the evidence supporting an
association between longer storage and adverse
clinical outcomes is scarce.
Critical Appraisal
 Study
design
 Follow-up
 Very large sample
 A key strength of this study is the unbiased
exposure and outcome ascertainment
 Study by definition was retrospective but
all data were collected prospectively
Critical Appraisal
 The
confidence in causal inference based
on observational study results is limited,
despite tight adjustments for the majority
of previously implicated confounding
factors
 Therefore, we need more convincing
evidence RCTs
Critical Appraisal
 Great
impact on the cost of blood
production
 Finally , would the results of this study
change my transfusion practice?
Thank you