Transcript Original Slide Presentation

Ammar Alsughayir
TM Fellow
Ottawa
Background


Platelet supply –inventory
Management
Platelet Antigen expression
Background
the effects of 393 transfusions of
pooled PLT products in pediatric
cancer patients between 1973 and
1974
 ABO matching had no effect on the
success of
a transfusion

van Eys J, Thomas D, Olivos B. Platelet use in pediatric
oncology: a review of 393 transfusions. Transfusion 1978;
18:169-73.
The TRAP trial
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
higher PLT increments after
transfusion of ABO-compatible PLTs.
In lymphoma patients undergoing
autologous marrow transplantation,
leukoreduced ABO identical PLT
transfusions were associated with
reduced morbidity ABO-mismatched
PLT transfusions may be associated
with a poor outcome
Factors affecting Response to
platelets TX

Platelet production
factors
• Whole blood
derived vs. APC
• storage conditions,
• storage time,
• PLT yield per
apheresis procedure
• increasing BW of
the recipient
favoured successful
transfusions
Study objective

The present prospective study was
designed to investigate the impact of
providing either ABO-identical or outof-group APCs to children with
thrombocytopenia suffering from
hematologic malignancies, solid
tumors, or aplastic anemia.
PATIENTS AND METHODS
Study design and objectives

Differences in transfusion
efficacy,measured by the 1-hour
percentage of PLT recovery (PPR1hr)
• ABO-identical vs major ABO- mismatched PLT

Secondary objectives were
• to compare the efficacy of ABO-identical PLT
transfusions with major mismatched
transfusions of group A subtypes A1 and A2 as
well as with minor-mismatched transfusions

side effects of PLT transfusions and data
on the production process of APCs were
recorded prospectively
Patients
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2004-2006
all consecutive
patients with
• hematologic
malignancies,
• solid tumors, or
• aplastic anemia

requiring at least one
PLT transfusion
Exclusion criteria were

refusal of study

fever of 38.5°C or
greater before
transfusion,
 clinically enlarged
spleen,

thrombosis,
 Adverse events
requiring interruption
of transfusion,
 Hemorrhage of WHO
Grade 3 or greater
Preparation and delivery of
PLTs
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PLTs were obtained from healthy volunteer
donors, either by single- or by double-needle
thrombocytapheresis using a cell separator
(Amicus Crescendo)
single-needle procedures using one of two
different cell separators (Trima Accel or COBE
Spectra)
Depending on the yield, the apheresis product
was split into units containing at least 2.0 x10 11
PLTs, corresponding to the minimum content
required by the standards of the Swiss Red Cross
at the time
Inventory management
guidelines
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Older products were delivered first .
ABO-identical products were provided first;
otherwise minor- or major-mismatched PLTs
were delivered at the discretion of the staff.
Wherever applicable no D+ PLTs were given to
D– female recipients.
Group O PLT donors were screened for the
presence of anti-A and anti-B hemolysins. If a
titer of more than 4 was present, the product was
labelled accordingly and released for group O
recipients only
PLT transfusions
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Most patients received prophylactic
PLT transfusions, with only a few
receiving PLT transfusions for
therapeutic purposes.
Children less than 2 years old
received half an APC product, and
patients aged 2 years or more
received a full APC product
independent of their BW.
Efficacy measures: PPR1hr and
1-hour CCI (CCI1hr)
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The CCI1hr allows to assess the
efficacy of PLT transfusion accounting
for the body surface area (BSA) and
the number of transfused PLTs
PPR1hr [%] = (posttransfusion count
[109/L] - pretransfusion count
[109/L]) x blood volume [L]/PLT
dose [1011/L]
Determination of A antigen expression and
A1/A2
subgroup typing
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For major-mismatched transfusions from
group A donors, A antigen expression on
PLT surfaces was measured by flow
cytometry both in the APC and in the
recipient before and 1 hour after
transfusion.
Fluorescent microscopy
• to identify glycoprotein IIIa on PLTs

Isohemagglutinin titer testing
• For patients and APCs
RESULTS
Patient characteristics, PLT transfusions, and
indications
Constellations of ABO blood group matching
of
donors and recipients
Interim analyses of the primary
study variable

The three planned interim analyses
did not result in a proposal to stop
the study early because of proven
difference or proven futility
PLT transfusion efficacy
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The median PPR1hr of all transfusions was 31
percent.
Univariate analysis showed PPR1hr for 76 major
mismatched transfusions to be significantly
inferior to that for 282 ABO-identical transfusions
(median, 21% vs. 32%; p = 0.034)
major-mismatched transfusions were significantly
more often unsuccessful than ABO-identical
transfusions (p = 0.033), especially many majormismatched transfusions from subgroup A1
donors failed (p = 0.002).
Major-mismatched A2 PLTs were as successful as
ABO-identical ones (p = 1.00
PLT transfusion efficacy
Multivariate analysis
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Major-mismatched transfusions were significantly
more often unsuccessful than ABO-identical
transfusions (p = 0.005).
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subgroup analysis revealed that PLTs from donors with ABO subgroup A2
given to group O or B recipients, although major mismatched transfusions,
by definition, were just as successful as ABO-identical PLTs (p = 0.90).
the failure rate of major-mismatched transfusions was even more striking
(p = 0.002).
Fate of transfused A antigen-positive
PLTs
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in the majority of group O and B recipients, no A antigenpositive PLTs were detectable in the circulation 1 hour after
transfusion.
after ABO-identical PLT transfusions from group A1 donors
to group A2 Recipients, whose RBCs but not PLTs express A
antigen, the majority of transfused A antigen positive PLTs
remained detectable in the circulation
Fluorescent microscopy of A antigen-positive
PLTs

using the MoAb anti-CD61 for identification of PLTs and
anti-A BRIC-145 for expression of A antigen, depletion of
transfused A antigen-positive PLTs from the circulation of a
blood group O recipient is visualized at a single-cell level by
dual-color fluorescent microscopy

Regression analysis
showed that for group
A major-mismatched
transfusions, there
was a significant
negative correlation (p
= 0.002) between the
percentage of A
antigen-positive PLTs
in the APC and the
PPR1hr; that is, the
more PLTs expressed
A antigen, the lower
the PPR1hr
Safety review and isohemagglutinin
titers
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no clinically detectable hemolytic transfusion reaction was
observed.
no association between transfusion efficacy and the
recipient’s isohemagglutinin titers were detected (data not
shown)
DISCUSSION
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ABO-incompatible PLTs may be associated with
decreased PLT increments after transfusion.
The majority of studies have been performed in
adult patients, and PLT transfusion in children is
poorly investigated
A randomized study design would have increased
the power of the study. However, in view of the
preceding studies in adults it is considered such
a design incompatible with good clinical practice
in this vulnerable pediatric population.
DISCUSSION
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statistical endpoints is based on CCI1hr
and PPR1hr as surrogate parameters for
PLT transfusion efficacy
CCI1hr accounts for BSA and is well
established in adults, whereas PPR1hr
accounts for BW and is reported to be
more appropriate in children, particularly
in infants and toddlers.
The final analysis was based on PPR1hr.
DISCUSSION

The results demonstrate that
transfusion efficacy and transfusion
success, the latter defined as PPR1hr
of more than 30 percent, of majormismatched PLTs are significantly
inferior to those of ABO-identical
PLTs, whereas efficacy and success of
minor-mismatched transfusions are
not different from those of identical
transfusions.
DISCUSSION
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diversity in the percentages of PLTs expressing A
antigen among A1 donors (median, 40%; range,
3%-80%).
the percentage of A antigen-expressing PLTs and
PPR1hr were inversely related; that is, the higher
the percentage of A antigen-expressing PLTs, the
lower the PPR1hr.
Median anti-A titers in the plasma of blood group
O recipients was higher than in plasma of group
B recipients , this may explain the slightly better
survival of transfused A1 PLTs in group B
recipients
A2 PLTs can be considered group O compatible
Critical Appraisal
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Prospective observational study .
Were all patients who entered the trial
properly accounted for at its conclusion?
Will the results help me in caring for my
patients?
Can the results be applied to my patient
care?
Were all clinically important outcomes
considered?
Conclusion
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major-mismatched PLT transfusions
were significantly less successful
than ABO-identical transfusions.
In children requiring regular and
continued PLT support, an ABOcompatible transfusion strategy
should be the first choice.
PLT concentrate suppliers would have
to provide A1/A2 subgroup typing of
group A PLT donors
Conclusion
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In this study, transfusion of plasmaincompatible PLTs was as successful
as that of identical PLTs, although an
inherent risk for hemolytic
transfusion reactions will remain
To volume reduce or not?
Will blood supplier or hospital test
donor for high titer Anti A once and
for all ?