REVIEW

CURRENT
OPINION ABO incompatible platelets: risks versus benefit
Nancy M. Dunbar a,b, Deborah L. Ornstein a,b, and Larry J. Dumont a

Purpose of review
The importance of ABO blood group system compatibility in platelet transfusion is a subject of ongoing
debate. Although there are theoretical advantages to pursuing a strict policy of providing exclusively
ABO-compatible products, resource challenges may make this untenable for many transfusion services.
Moreover, data supporting a net clinical benefit for this practice have been lacking. This review
summarizes recent developments in the area of ABO compatibility and platelet transfusion and examines
the risks and benefits associated with transfusion practices allowing for platelet ABO incompatibility.
Recent findings
ABO-major incompatible transfusions are associated with lower platelet count increments than either ABO
identical or minor incompatible transfusions and may lead to decreased intervals between platelet
transfusions in thrombocytopenic patients. ABO-minor incompatible transfusions may rarely result in acute
hemolytic reactions that are not predicted by isohemagglutinin titers. Yet published evidence to date does
not clearly demonstrate improvements in clinical outcomes for patients receiving ABO-identical or ABO-
compatible platelets. Adherence to a strict policy of transfusing exclusively ABO-identical platelets may lead
to an increase in product wastage and challenges in maintaining adequate platelet availability.
Summary
There is presently limited data and no consensus on the best approach for managing ABO compatibility in
platelet transfusions. Well designed, sufficiently powered randomized clinical trials are urgently needed.
These studies must examine not only safety and efficacy of various ABO matching strategies but also
clinical benefit and resource utilization in order to identify optimal platelet transfusion strategies.
Keywords
ABO, hemolysis, isohemagglutinins, platelets, transfusion

INTRODUCTION decreased response to platelet transfusion. This find-

The importance of ABO compatibility in platelet
transfusion is a subject of longstanding and ongoing
debate. Transfusion of ABO-nonidentical red blood
cells (RBCs) and plasma is seldom performed, and
then only with particular care to assure that trans-
fused RBCs are compatible with the patient plasma,
and that large volume plasma transfusion is compat-
ible with the patient RBC type. Yet, platelets are
routinely transfused across ABO barriers. There are
two advantages to this practice: first, availability –
ABO-identical platelets are not always in the inven-
tory or, in emergency situations, the patient ABO
type may be unknown; and second, avoidance of
platelet wastage – with a short shelf life of 5 days,
last-in-first-out inventory management is often given
priority over ABO matching. On the other hand,
transfusion of ABO-nonidentical platelets may cause
such harms as acute hemolysis, fever, alloimmuniza-
tion, inflammation, and reduced efficacy.
As reviewed by Cooling [1], transfusion of major
ABO incompatible platelets is associated with a
ing is attributed to expression of ABH antigens on
the platelet surface that in turn leads to clearance by
isohemagglutinins in the platelet recipient. Trans-
fusion of ABO-minor incompatible platelets exposes
the recipient to ABO-incompatible plasma and has
been associated with multiple case reports of acute
hemolytic transfusion reactions [1]. Between 1996
and 2006, there were six deaths attributed to hemo-
lysis in the setting of minor incompatible platelet
transfusion reported to the US Food and Drug
Administration [2]. Despite these potential pitfalls,
a
Department of Pathology, Center for Transfusion Medicine Research,
the Geisel School of Medicine at Dartmouth and bDepartment of Medi-
cine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire,
USA
Correspondence to Larry J. Dumont, MBA, PhD, One Medical Center
Drive, Lebanon, NH 03756-0001, USA. Tel: +1 603 650 5000; fax: +1
603 650 4845; e-mail: Larry.J.Dumont@hitchcock.org
Curr Opin Hematol 2012, 19:475–479
DOI:10.1097/MOH.0b013e328358b135

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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Transfusion medicine and immunohematology
KEY POINTS
 Transfusion services and treating physicians should be
aware of the potential for adverse consequences of
transfusing ABO-nonidentical platelets.
 Platelet ABO-major incompatibility may decrease the
efficacy of platelet transfusions, whereas ABO-minor
incompatibility may be associated with hemolytic
transfusion reactions.
 The best approach to managing ABO incompatibility in
platelet transfusions remains unknown and decisions
must be influenced by transfusion safety, efficacy and
resource availability and utilization.
 Transfusion services should develop and follow specific
policies related to ABO-nonidentical
platelet transfusions.
 Methods to reduce the risks of minor-mismatched
platelets, such as antibody screening and plasma
replacement with additive solutions, are available and
should be considered.
data to support a net clinical benefit for exclusive
use of ABO-identical platelets are lacking.
Recognizing the possible adverse effects from
ABO-incompatible transfusion, the AABB, the
American College of Pathology, and other standards
bodies require that transfusion services have written
policies for administration of ABO-incompatible
platelets [3–5]. A recent Biomedical Excellence for
Safer Transfusion Collaborative (BEST) collaborative
international survey revealed that there is significant
practice variation in providing ABO-incompatible
platelets, with 19.4% of 126 respondents lacking
a written policy for releasing ABO-incompatible
platelet concentrates [6]. The authors concluded
that this practice variation demonstrates a need
for continued research to inform evidence-based
platelet transfusion practice. This review summar-
izes recent developments in the area of ABO and
platelet transfusion.
ABO-IDENTICAL PLATELET TRANSFUSION
Shehata et al. [7] reviewed ABO-identical versus non-
identical platelet transfusion practices. This review
of three randomized controlled trials and 16 obser-
vational studies concluded that ABO-identical
platelet transfusions result in a higher platelet
increment than ABO-nonidentical transfusions.
However, the overall clinical benefit of that
increased increment is unclear as none of the studies
included in this review incorporated mortality,
bleeding events or transfusion reactions as primary
endpoints. Moreover, none of the trials were
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sufficiently powered to evaluate these important
events. Accordingly, the data were inconclusive as
to whether or not the use of ABO-identical platelets
resulted in improved patient outcomes compared
with ABO-nonidentical platelets. A policy change
requiring ABO-identical platelet transfusions would
have significant impacts on transfusion services
given the limited availability of platelet products
due to the short outdate of this component as well as
to donor logistics. Therefore, the authors concluded
that a large randomized controlled trial is needed to
clarify the degree of benefit that is conferred by
ABO-identical platelets for transfusion.
In spite of the lack of conclusive evidence sup-
porting improved outcomes in patients who receive
ABO-identical platelet transfusion, some trans-
fusion services have adopted this approach. In
2005, the University of Rochester implemented a
policy of providing ABO-identical platelets to all
patients whenever possible, regardless of the out-
dating and logistical considerations that commonly
impact platelet transfusion choices. In a before
and after observational study in surgical patients,
transfusion of ABO-identical or washed platelets
resulted in significant reductions in febrile and
allergic transfusion reactions as well as RBC alloim-
munization. This practice was associated with a
5.6% increase in platelet outdating for this group
&
[8 ].
ABO MAJOR INCOMPATIBLE PLATELET
TRANSFUSION
Transfusion of major incompatible platelets has
been associated with lower posttransfusion platelet
count increments than ABO-identical or minor
&&
incompatible platelets [9]. Triulzi et al. [10 ] re-
addressed the effects of ABO-compatible platelet
transfusions in an examination of the Determi-
nation of the Optimal Prophylactic Platelet Dose
to Prevent Bleeding in Thrombocytopenic Patients
(PLADO) clinical trial database. The PLADO trial was
a prospective, randomized controlled trial that
investigated the efficacy of three different platelet
doses for transfusing thrombocytopenic patients
[11]. The primary outcome analyzed by Triulzi
et al. was the time to WHO grade 2 or higher bleed-
ing following the first transfusion to the patient. The
investigators compared the effects of platelet trans-
fusion with ABO-identical, ABO-major compatible
and ABO-minor compatible platelets. After trans-
fusion, platelet count increments and the interval
between transfusions were also analyzed. They
determined that platelet ABO matching status was
not predictive of the time to grade 2 or higher
bleeding. Major ABO-compatible platelets were
Volume 19  Number 6  November 2012
 ABO incompatible platelets: risks versus benefit Dunbar et al.
associated with lower 4 and 24 h posttransfusion
absolute and corrected count increments when
compared with ABO-identical platelets, a difference
not observed for ABO-minor incompatible platelet
transfusions. These differences resulted in a slightly
shorter interval to the next platelet transfusion for
patients receiving ABO-major incompatible plate-
lets (3.9 h shorter median transfusion interval);
however, ABO matching status had no impact on
prevention of clinical bleeding. Although these
findings confirm previous studies, these small differ-
ences in posttransfusion increments do not appear
to confer a greater risk for bleeding when following
the PLADO transfusion strategy.
Another recent study investigated the effect of
major incompatible transfusion on in-vitro platelet
function and found that exposure of major incom-
patible platelets to group O plasma with moderate
to high titer anti-A/B resulted in measurable effects
on platelet function including inhibition of platelet
aggregation, and prolonged PFA-100 epinephrine
&
closure times [12 ]. This finding suggests that, in
addition to diminished posttransfusion incre-
ments, platelet function may be impaired when
patients receive ABO-major incompatible platelets.
The clinical significance of this observation is ques-
tionable, however, in view of the findings of the
secondary analysis of the PLADO trial described
above.
Adding to the complexity of this topic, platelet
ABO compatibility also appears to play a role in
posttransfusion count increments in patients
requiring human leukocyte antigen (HLA) selected
platelets. In a recent study evaluating complement
C1q binding solid phase HLA antibody testing for
immune refractory patients, the impact of ABO
&
compatibility was also assessed [13 ]. A subset of
patients receiving C1q compatible platelets (i.e.,
HLA compatible) demonstrated significantly higher
CCI when ABO-major compatible platelets were
transfused. This finding is provocative and implies
that ABO-major compatibility should be considered
when selecting platelets for HLA-sensitized individ-
uals whenever possible. However, resource availabil-
ity may make this approach challenging for many
centers, and the clinical benefit is unproven.
ABO-MINOR INCOMPATIBLE PLATELET
TRANSFUSION
Whereas transfusion efficacy is of concern with
ABO-major incompatible platelet transfusions, the
primary concern with ABO-minor incompatible
platelet transfusions is intravascular hemolysis. A
recent retrospective database review of Medicare
claims detected three ABO incompatible events
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among 59 993 platelet transfusions, suggesting the
rate of hemolysis associated with ABO-minor
incompatible platelet transfusion is low [50 per
million, 95% confidence interval (CI) 10–146]
&&
[14 ]. On the basis of multiple case reports, hemo-
lysis typically occurs after transfusion of a group O
platelet containing high titer anti-A to a group A
recipient [1]. However, recent identification of a
group A platelet donor with high titer anti-B that
was attributed to probiotic use raises the possibility
of an increased risk of hemolysis with any minor
incompatible platelet transfusion [15]. In contrast, a
recent study of blood donors showed no increase in
ABO or HLA antibody levels following influenza
&
vaccination [16 ].
Approaches to the risk of hemolysis with ABO-
minor incompatible platelet transfusion vary
dramatically around the world. The BEST Collabo-
rative international survey of transfusion services
highlighted a lack of uniformity of transfusion prac-
tice when ABO-identical platelets are unavailable
[6]. Among services transfusing apheresis platelet
concentrates suspended in plasma, 54% indicated
that they would select ABO-minor compatible
platelets in this setting, whereas 29.9% would select
any available platelet. If minor incompatible plate-
lets were selected, 48.1% of respondents would take
no further action, whereas 37.7% would select
platelets with low titer isohemagglutinins. Results
were similar for buffy coat derived platelets in
plasma.
Anti-A and anti-B titers have been reported to be
comparable between group O single donor platelets
and group O pooled platelet concentrates [17]. In
the United States, universal agreement on a critical
titer that defines a safe level for minor incompatible
platelet transfusion has remained elusive [18].
Methodologies for determining titers include tube
and gel test systems, which complicates the ability
to compare results between different institutions.
The National Institutes of Health recently reported
on their approach to screening group O platelet
donors using the gel method with reactivity at a
plasma dilution of 1 : 250 used to define high titer
&&
donors [19 ]. Approximately 25% of group O
platelets were identified as having high titer ABO
antibodies using this approach and were either
given exclusively to group O patients or washed
to remove the incompatible plasma. Since imple-
menting this approach, they have not observed any
platelet-associated hemolytic transfusion reactions
at their institution.
A recent review of ABO-minor incompatible
platelet transfusions evaluated by the gel method
for measuring anti-A and anti-B titers prior to pro-
duct release suggests that a critical isohemagglutinin
www.co-hematology.com 477
 Transfusion medicine and immunohematology
titer may not alone predict transfusion-related
&
hemolysis [20 ]. This study identified 647 ABO-
minor incompatible platelet transfusion recipients,
73 of whom received platelet transfusion of a prod-
uct with a titer of 1 : 256 or greater and 27 with a titer
of 1 : 512 of greater. Analyzing all passively reported
transfusion reactions, the transfusion service noted
that they received no reports of hemolytic trans-
fusion reactions for patients who received these
ABO-minor incompatible platelet transfusions and
only two reports of fever/chill reactions with
positive direct antiglobulin tests. This suggests that
while diversion of ABO-minor incompatible plate-
lets with critical titers may prevent hemolytic trans-
fusion reactions, transfusion services considering
implementation of a critical titer may not see a
measurable decrease in reports of what is already a
relatively rare event.
There are alternatives to measuring isohemag-
glutinin titers to decrease the risk of hemolysis from
ABO-minor incompatible platelets. Preparation of
buffy coat platelets suspended in platelet additive
solution is practiced in Europe and may be associ-
ated with decreased risk for hemolysis due to the
reduction in plasma volume [18]. The current status
of platelet additive solution use has been recently
&
reviewed [21 ]. Where additive solutions are not
available, one may perform plasma volume
reduction of the platelet product when ABO-minor
incompatibility cannot be avoided. This approach
has recently been described for providing HLA/
human platelet antigen-matched products to
alloimmunized adults, but is associated with lower
&
corrected count increments [22 ]. Platelet washing
may also be employed when ABO-identical platelets
are not available but at the hazard of decreased
transfusion efficacy. Another approach that has
been described recently is the preparation of
hyper-concentrated platelets (i.e., dry platelets),
typically with suspension in an additive solution
during storage [23]. Although available for several
years in many countries outside of the Unites States,
only recently has a platelet additive solution for use
with apheresis platelets been approved by the US
Food and Drug Administration [24]. There is con-
tinuing work to extend this availability by other
commercial suppliers [25] as well as to explore even
more dramatic reduction in plasma carryover to 5%
[26]. Other authors have proposed plasma replace-
&
ment using AB plasma [27 ]. Although theoretically
this approach would allow for ‘universally compat-
ible’ platelet transfusions, it is uncertain whether
diversion of AB plasma for this purpose is feasible
given the relative scarcity of this product. The net
clinical benefit of any of these approaches remains
to be determined.
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CONCLUSION
When considering the optimal approach to ABO-
matching and platelet transfusion, it is important to
appreciate the complexity of this problem both in
terms of different degrees of platelet incompatibility
(major, minor, bidirectional) and resource availabil-
ity challenges. Although ABO-identical transfusions
may be ideal, lack of platelet availability makes this
approach impractical for most transfusion services.
Those that do strive to provide ABO-identical pla-
telet components whenever possible may have to
resort to further product modification, such as wash-
ing or volume reduction, when this goal cannot be
realized. These modifications may minimize the
risks associated with minor incompatibility but do
not address issues related to major incompatibility
and may result in reduced transfusion efficacy. Even
at institutions that have adopted strict policies to
address platelet incompatibility, concessions must
be made for special patient populations such as
highly alloimmunized patients requiring HLA-
matched platelets that may not be ABO-compatible.
Clearly, although work continues in this field, there
is currently no consensus on the best approach to
take for managing platelet transfusions and ABO
compatibility. Well designed, sufficiently powered
randomized clinical trials are still needed to answer
this important question on the balance of risks and
benefits of ABO-incompatible platelet transfusions.
Acknowledgements
None.
Conflicts of interest
L.J.D. has received research support from Terumo BCT,
Inc., and Fenwal, Inc.
For the remaining authors no conflicts of interest were
declared.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
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www.co-hematology.com 479